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_ -NOTE: For additional volumes ptease contact the Canadian Patent Office FIELD OF THE INVENTION
The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.
BACKGROUND OF THE INVENTION
Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation; or interaction with other cells, is typically governed by information received from other cells andlor the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenicfactors, survival factors, cytotoxic factors; differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. These secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the extracellular environment.
Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors. Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins.
Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents. Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and technidues are described in the literature [see, for example, KIein et aL, Proc. Natl. Acad. Sci. 93:7108-7113 (199'6); U.S. Patent No. 5,536,637)].
Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g.; proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells andlor the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse; cell receptors or membrane-bound proteins.
Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transducaon of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound'. proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptorlligand interaction.
Efforts are being undertaken by bout industry and academia to identify new, native receptor or membrane-bound proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor or membrane-bound proteins.
I. PR01560 The tetraspan family of proteins has grown to include approximately 20 known genes from various species, including drosophila. The tetraspans are also known as the transmembrane 4 (TM4) superfamily and are proposed to have an organizing function in the cell membrane. 'Their ability to interact with other molecules and function in such diverse activities as cell adhesion, activatiion and differentiation, point to a role of aggregating large molecular complexes. Skubitz, et ai., J. ImmunoloQV.
157:3617-3626 (1996). The tetraspan group has also emerged as a set of proteins with prominent functions in Schwann cell biology. Mirsky and Jessen, Curr. Opin. Neurobiol., 6(1):89-96 (1996). Tetraspans (also sometimes called tetraspanins} are further described in Maecker, et al., FASEB. 11:428-442 (1997). Thus, members of the tetraspan family are of interest.
2. PR0444 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR0444.
3. PR01018 Efforts are being undertaken by both industry and academia. to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences far novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated Herein as PR01018.
4. PROI773 The primary and rate-limiting step in retinoic acid biosynthesis requires the conversion of retinoi to retinal. RetinoI dehydrogenase proteins are enzymes which function to recognize holo-cellular retinol-binding protein as a substrate, thereby catalyzing the first step of retinoic acid biogenesis from its substrate. Various retinol dehydrogenase genes have been cloned and characterized, wherein the products of these genes are suggested as potentially being useful for the treatment of retittitis pigtnentosa, psoriasis, acne and various cancers (Chaff et al., J. Biol. Chem. 270:28408-28412 (1995} and Chaff et al., Gene 169:219-222 (1996)). Given the obvious importance of the retinol dehydrogenase enzymes, there is significant interest in the identification and characterization of novel polypeptides having homology to a retinoi dehydrogenase. We herein describe the identification and characterization of novel polypeptides having homology to a retinol dehydrogenase protein, designated herein as PR01773 polypeptides.
5. PR01477 Glycosylation is an important mechanism for modulating the physiochemical and biological properties of proteins in a stage- and tissue-specific manner. One of the important enzymes involved in glycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, an enzyme that catalyzes the conversion of Man9GlcNAc2 to ManBGIcNAc2 during the formation of N-linked oligosaccharides. The Saccharomyces cerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class I alpha 1,2-mannosidases that are conserved from yeast to mammals. Given the important roles played by the alpha 1,2-manaosidases and the mannosidases in general in glycosylation and the physiochemical activity regulated by glycosylation, there is significant interest in identifying novel poiypeptides having homology to one or more mannosidases. We herein describe the identification and characterization of novel polypeptides having homology to a mannosidase protein, designated herein as PROI477 polypeptides.
6. PR01478 Recently, a new subfamily of galactosyltransferase genes that encode type II
transmembrane proteins was identified from a mouse genomic library (Rennet et al., (1998) J. Biol.
Chem. 273(1):58-65).
Galactosyluansferases, in general, are all of interest. Beta 1,4-galactosyltransferase is been found in~two subcellular compartments where it is believed to perform two distinct function. Evans, et al., ssa s 17(3):261-268 (1995). Beta 1,4-galactosyltransferase is described .as a possible transducing receptor in Dubois and Shur, Adv. Exp. Med. Biol. 376:105-114 (1995), and further reported on in Shur, GlvcobiqlQ,gy, 1(6):563-575 (i99i). Expression and function of cell surface galactosyltr<~nsferase is reported on in Shur, Bi him.
Biophvs. Acta., 988(3):389-409 (1989). Moreover, the receptor function of galactosyltransferase during mammalian fertilization is described in Shur, Adv. ERt). Biol., 207:79-93 (1986), and the receptor function during cellular interactions is described in Shur, Mol. Cell Biochem., 61(2):143-158 (1984). Thus, it is understood that galactosyltransferases and their related proteins are of interest.
7. PR0831 Efforts are being undertaken by both industry and academiia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the idE;ntification and characterization of a novel secreted protein designated herein as PR0831.
8. PRO11I3 Protein-proteininteractions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein WO 00/12708 PCTlUS99/2011 I
interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations: The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci... 19(10):415-4.21 (Oct. 1994).
A study has been reported an leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound heating, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit., Rev. Biochem.
Mol. Biol., 32(2):141-I74 (I997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. HematoI. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Souliier syndrome, Chlemetson, K. J., Thromb.
Haemost. (Germany}, 74( 1):111-116 {July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor[3 has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-heating and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the iGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1., a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobuIin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et ai., Mol. Cell Endocrinol., (Ireland), 125(1-2):65-70 (Dec. 1996} (gonadotropin receptor involvement); Miura, Y., et al., hlippon Rinsho (Japan), 54{7):1784-1789 (July 1996) (apoptosis involvement}; Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 {Oct. 1995) (kidney disease involvement).
9. PR01194 The nuclear genes PET117 and PET119 are required for tl a assembly of active cytochrome c oxidase in S. Cerevisiae, and therefore, are of interest. Also of interest are;
nucleic acids which have sequence identity with these genes. PET genes are further described in McEwen, et al., Curr.
Genet., 23{1):9-14 (1993).
10. PRO1110 The bone marrow plays many important roles in the mammal. One of those roles is to provide a source of various progenitor cells that differentiate into important cells and other components of the blood and immune systems. As such, the function of the myeloid system is of extreme interest.
We herein describe the identification and characterization of novel polypeptides having homology to myeloid upregulated protein, designated herein as PRO1110 poly~peptides.
11. PR01378 Efforts are being undertaken by both industry and acadernia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant . DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01378.
12. PR01481 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel proteins. We herein describe the identification and characterization of a novel protein designated herein as PROI481.
13. PR01189 There has been much interest in the identification of recepu~r proteins on stem cells and progenitor cells which may be involved in triggering proliferation or differentiation. A type II transmembrane protein was identified in proliferating progenitor cells in the outer perichondrial rim of the postnatal mandibular condyle proliferation. The investigators concluded that E25 could be a useful marker for chondro-osteogenic differentiation (Deleersnijder, et ai. J. Biol. Chem. 271132);1947~~-19482 (1996)).
14. PR01415 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the ideneification and characterization of a novel transmembrane polypeptide designated herein as PR01415.
1S. PR01411 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01411.
16. PR01295 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01295.
17. PR01359 Enzymes such as hyaluronidase, siaiyltransferase, urokinase-type plasminogenactivator, plasmin, matrix rnetalloproteinases, and others, play central roles in the catabolism of extracellular matrix molecules. As such, these enzymes and inhibitors thereof, may play roles in metastatic cancer and the treatment thereof. Van Aswegen and du Plessis, Med. Hypotheses. 48(5):443-447 (1997)., For the foregoing reason, as well as their diversity in substrate specificity example, sialyltransferases are of particular interest. For example, a peptide of interest is the GaINAc alpha 2, 6-sailytransferase as descril5ed in Kurosawa, et al., J. Biol. Chem., 269(2):1402-1409 (1994). This peptide was constructed to be secreted, and retained its catalytic activity. The expressed enzyme exhibited activity toward asialomucin and asialof~etuin, but not other glycoproteins tested. As sialylation is an important function, sialyltransferases such as this one, and peptides related by sequence identity, are of interest. Sialyltransferases are further described in the literature, see for example, Sjoberg, et al, 3. Biol.
Chern., 271(13):7450-7459 (1996), Tsuji, J. Biochem., 120(1):1-13 (1996) and Harduin-Lepers, et al., Glycobioloev, 5{8):741-758 (I995).
18. PR01190 Kang et al. reported the identification a novel cell surface glycoprotein of the Ig superfamily (J. Cell biol. (1997) 38 1 :203-213). Cell adhesion molecules of the Ig superfamily are implicated in a wide variety of biological processes, including cell migration, growth control, and tumorigenesis. The Kang et al, studies suggest that loss of CDO function may play a role in oncogenesis. Accordingly, the identification of additional CDO-like molecules, and more generally, cell adhesion molecules of the Ig superfamily, is of interest.
I9. ROI772 Peptidases are enzymatic proteins that function to cleave peptide substrates either in a specific or non specific manner. Peptidases are generally involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numernus different peptidase enzymes from a variety of different mammalian and non-mammalian organisms have been both identiified and characterized. The mammalian peptidase enzymes play important roles in.many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
In light of the important physiological roles played by peptidase enzymes, efforts are currently being undertaken by both industry and academia to identify new, native peptidase hornologs. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad: Sci , 93:7108-7t 13 (1996};
U.S. Patent No. 5,536,637)]. We herein describe the identification of novel polypeptides having homology to various peptidase enzymes, designated herein as PROI772 poiypeptides.
20. PR01248 Putative protein-2 (PUT-2) is a homolog of the human disease genes Ll CAM, G6PD and P55 (Riboldi Tunnicliffe et al., Genome Anaivsis, submitted). As such, there is interest in identifying novel poiypeptides and encoding DNA having homology to the PUT-2 protein. We herein describe the identification and characterization of novel polypeptides having homology to PUT-2 protein, designated herein as PR01248 polypeptides.
IO
21. PROI31G
Dickkopf (Dkk) is a family of secreted proteins having a high degree of homology in the cysteine-rich domains {i.e., 80-90% ). Dkk-l, the first discovered member, of this family has potent head-inducgin activity on the Spemann organizer. Glinka et al., Nature 391 (6665): 357-362 (1988).
The Spemann organizer of the amphibian embryo can be subdivided into two discrete activities, namely trunk organizer anri head organizer.
Dkk-1 has been found to be both sufficient and necessary to cause head induction in Xenopus embryos and is further a potent antagonist of Wnt signaling, suggesting that the :Dkk genes encode an entire family of Wnt inhibitors.
Members of the Wnt gene family function in both normal development and differentiation as well as in tumorigenesis. Wnts are encoded by a large gene family whose members have been found in round worms, insects, cartilaginous fish, and vertebrates. Holland et al., Dev. Suppl., I25-I33 (1994). Wnt genes encode a family of secreted glycoproteins that modulate cell fate and behavior in embryos through activation of receptor-mediated signaling pathways.
Studies of mutations in Wnt genes have indicated a role for Wnts in growth control and tissue patterning. In Drosophila, wingless (wg) encodes a Wnt-related gene; (Rijsewik et al.; Celt, 50: 649-657 (I987)) and wg mutations alter the pattern of embryonic ectoderm, neurogenesis, and imaginal disc outgrowth. Morata and Lawerence, Dev. Biol., 56: 227-240 (1977}; Baker, Dev. Biol., 125: 96-108 {1988); Kiingensmith and Nusse, Dev. Biol., 166: 396-414 (1994). In Caenorhabditis elegans, lin-44 encodes a Wnt homolog which is required for asymmetric cell divisions. Herman and Horvitz, Development, 120:
1035-1047 (1994}. Knock-out mutations in mice have shown Wnts to be essential for brain development (McMahon and Bradley, Cell, 62:
1073-1085 (1990); Thomas and Cappechi, Nature, 346: 847-850 {1990)), and the outgrowth of embryotuc primordia for kidney (Stark et al., Nature, 372: 679-683 (1994))" tail bud (Takada et al., Genes Dev., 8:
174-189 (1994)), and limb bud. Patr and McMahon, Nature, 374: 350-353 (1995).
Overexpression of Wnts in the mammary gland can result in matntnary hyperplasia and tumors, ((McMahon, supra (1992); Nusse and Varmus, H.E., Ceil 69: 1073-1087 (1992)), and precocious alveolar development.
Bradbury et al., Dev. Biol., 170: 553-563 (1995). Moreover, constitutive expression of Wnt-4 in virgin hosts of transplanted mammary epithelium resulted in highly branched tissue, similar to a pregnancy-like growth pattern. Bradbury et ai., Dev.
Biol. 170: 553-563 (1995).
The WntlWg signal uansduction pathway plays an important role in the biological development of the organism and has been implicated in several human cancers. This pathway also includes the tumor suppressor gene, APC. Mutations in the APC gene are associated with the development of sporadic and inherited forms of human colorectal cancer. For example, elevated levels of Wnt-2 have been observed in colorectal cancers.
Vider, B-Z. et al., Oncogene 12: 153-158 (1996).
22. PR01197 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding 1Q sequences for novel secreted proteins. We herein describe the idc;ntification and characterization of a novel secreted protein designated herein as PR01197.
23. PR01293 Immunoglobulins are antibody molecules, the proteins that :function both as receptors for antigen on the B-cell membrane and as the secreted products of the plasma cell. Like all antibody molecules, imrnunoglobulins perform iwo major functions: they bind specifically to an antigen amd they participate in a limited number of biological effector functions. Therefore, new members of the lg superfamily and fragments thereof are always of interest. Molecules which act as receptors by various viruses and those which act to regulate immune function are of particular interest. Also of particular interest are those molecules which have homology to /mown ig family members which act as virus receptors or regulate immune function. Thus, molecules having homology to Ig superfamily members and fragments thereof (i.e., heavy and light chain fragments) are of particular interest.
We herein describe the identification and characterization of novel polypeptides having hotnology to an immunoglobulin heavy chain variable region protein, designated herein as.
PR01293 polypeptides.
24. PR01380 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transraembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01380.
25. ~ PR012b5 The identification of novel secreted proteins involved in physiological and metabolic pathways is of interest because of their potential use as pharmaceutical agents. Of particular interest is the identification of novel polypeptides that are potentially involved in immune response and inflammation mechanisms. A novel polypeptide has recently been identified that is expressed in mouse. B cells in response to IL-4. The gene encoding this polypeptide is referred to as interleukin-four induced gene 1, or "Figl" (Chn et al. Proc. Natl:
wo aan27a8 PCT/US99120111 Acad. Sci (i997) 94(6):2507-2512).
26. PROI250 Long chain fatty acid CoA ligase is an enzymatic protein drat functions to ligate together long chain fatty acids, a function that plays important roles in a variety of different physiological processes. Given the S importance of this enzymatic protein, efforts are currently being 'undertaken to identify novel long chain fatty acid CoA iigase homologs. We herein describe the identifcation and characterization of novel polypeptides having homology to long chain fatty acid CoA Iigase, designated herein as PR012S0 polypeptides.
27. PROI475 N-acetylgIucosaminyltransferase proteins comprise a family of enzymes that provide for a variety of important biological functions in the mammalian organism. As an example, UDP-N-acetylglucosamine: alpha-3-D-mannoside beat-1,2-N-acetylglucosaminyltransferase I is an enzymatic protein that catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al., Proc. Natl.
Acad. Sci. USA. 88:234-238 (1991). Given the obvious importance of the N-acetylglucosaminyltransferase i S enzymes, there is significant interest in the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyitransferase protein. We herein describe the identification and characterization of novel polypeptides having homology to an N-acetylglucosaminyltransferase protein, designated herein as PR01475 polypeptides.
28. PR01377 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01377.
29. PR01326 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the ide;nt'tftcation and characterizarion of a novel secreted protein designated herein as PR01326.
3a. PROi249 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to 3S identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01249.
31. PR_ 01315 Many important cytokine proteins have been identified and characterized and shown to signal through specific cell surface receptor completes. For example, the class II cytokine receptor family (CRF2} includes the interferon receptors, the interleukin-I0 receptor and the tissue factor CRFB4 (Spencer et al., J. Exp. Med.
187:571-578 (1998) and Kotenko et al., EMBO J. 16:5894-5903 (1997)). Thus, the multitude of biological activities exhibited by the various cytokine proteins is absolutely dependent upon the presence of cytokine receptor proteins on the surface of target cells: There is, therefore, a significant interest in identifying and characterizing novel polypeptides having homology to one or more of the cytokine receptor family. We herein describe the identification and characterization of a novel polygeptide having homology to cytokine receptor family-4 proteins, designated herein as PR01315 polypeptides.
32. PR01599 Granzyme M is a natural killer cell serine protease. The; human gene is 7.5 kilabases, has an ezon-intron structure identical to other serine prote:ases; and is closely linked to the serine protease gene cluster on chromosome 19p13.3. (Pilaf et al., Genomics, 24:445-450 {1994)),. Granzyme M
has been found in two human natural killer leukemia cell lines, unstimulated human peripheral blood monocytes and untreated purified CD3-CD56+ large granular lymphocytes. (Smyth et al., J. Immunol.. 151:6195-6205 (1993)).
33. PR01430 Reductases form a large class of enzymatic proteins foundl in a variety of mammalian tissues and play many important roles for the proper functioning of these tissues. They are antioxidant enzymes that catalyze the conversion of reactive oxygen species to water. Abnormal leveels or functioning of reductases have been implicated in several diseases and disorders including strokes, heart attacks, oxidative stress, hypertension and the development of both benign and malignant tumors. For example, malignant prostate epithelium may have lowered expression of such antioxidant enzymes (Baker et aL, Prostate 32(4):229-233 {1997)j. International patent application no. W09622360-A1 describes a prostate specific. redtictase that is useful for diagnosing and treating prostate cancer and screening new antagonists. Inhibitors of alpha-reductase have been used in the treatment of benign prostatic hypetpIasia (Anderson, Drues Asine.(1996) 6j5,~388-396). For these reasons, the identification of new members of the reductase family has been of interest for tire treatment and diagttasis of cancers and other diseases and disorders.
34. PR01374 P'rolyl 4-hyroxylase (P4HA) catalyzes the formation of 4-hydroxyproline in coliagens. Annunen, et al., J. Biol. Chem., 272{28):17342-17348 (1997); Helaakoski, et al., fNAS USA, 92(10):4427-4431 (I995); and Hopkinson, et al., Gene, 149(2):391-392 (1994). This enzyme and molecules related thereto are of interest.
35. PR01311 The tetraspan family of proteins, also referred to as the "transmernbrane 4 (TM4) superfamily", are proposed to have an organizing function in the cell membrane. It is believed that they interact with large molecular complexes and function in such diverse activities as cell adhesion, activation and differentiation (see Maecker et al. F SEB (1997) 11:428-442). Accordingly, the identification of new members of the tetraspan family of proteins is of interest. Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins.
36. PR01357 Ebnerin is a cell surface protein associated with von Ebner glands in mammals.
Efforts are being undertaken by both industry and academia to identify new, native proteins and specifically those which possess sequence homology to cell surface proteins such as ebnerin or other salivary gland-associated proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins. We herein describe the identification of novel polypeptides having significant homology to the von Ebner minor salivary gland-associated protein, designated herein as PR01357 polypeptides.
37. PR01244 One type of transmembrane protein that has received attention is implantation-associateduterine protein.
Deficiencies or abnormalities of this protein may be a cause of miscarriage.
Therefore, the identification and characterization of implantation-associated proteins is of interest.
38. PR01246 Bone-related sulphatase is an enzymatic protein that has been shown to degrade sulphate groups of proteoglycan sugar chains in bone tissue (Australian Patent Publication No. AU
93144921-A, March 3; 1994).
Because of its specific sulphatase activity, it has been suggested than bone-related sulphatase may fmd use in the treatment of bone metabolic diseases. As such, there is significant interest in identifying and characterizing novel polypeptides having sequence similarity to bone-related suiphatase. We herein describe the identification and characterization of novel polypeptides having homology to bone-related sulphatase, designated herein as PR01246 polypeptides.
39. PR01356 Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)). CPE carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. cDNAs encoding the CPE-R protein have been identified characterized in both human and mouse (Katahira et al., J. Cell Biol. 136:1239-1247 (1997) and Katahzra et al., J. Biol. Chem. 272:26652-26658 (1997)): Since the CPE toxin has been repotted to cause a variety of illnesses in mammalian hosts and those illnesses are initiated by binding of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PR01356 polypeptides.
40. PR01275 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01275. .
41. PR01274 Efforts are being undertaken by both industry and acadetrtia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the icfentification and characterization of a novel secreted protein designated herein as PR01274.
42. PR01412 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Matry efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01412.
43. PR01557 The identification of secretory proteins that play roles ins neural development are of interest. Such proteins may fmd use in the understanding of and possible ueaunent of neurological diseases and disorders.
Chordin protein, which has been isolated from Xenopus, is a potent dorsalizing factor that regulates cell-cell interactions in the organizing centers of Xenopus head, trunk and tail development (Sasai et al., (1994) C~II
79(5):779-790; see also Mullins, (1998) Trends Genet. 1414):127-1.29; and Kessel et al. (1998) ) Trends Genet.
14(5):169-171). It may be used as a component of culture medium for culturing nerve and muscle cells, and may have use in the treatment of neurodegenerative diseases and neural injury (U.S. Pat. No. 5,679,783).
44. PR01286 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01286.
WO 00/12708 PCTlUS99120111 45. PR01294 The extracelIular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transductio~n machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al., Proc. Natl. Acad. Sci. USA
90:4655-4659 (I993), Bal et al.; Biochemistry 32:1047-1053 (I99:3) and Snyder et al., Biochemistry 30:9143-9153 (1991)). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides havvig homology to oIfactomedin. We herein describe the identification and characterization of a novel polypeptide having homology to olfactomedin protein.
We herein describe the identification and characterization. of novel polypeptides having homology to olfactomedin protein, designated herein as PR01294 golypeptides.
46. PR01347 ButyrophiIin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA
has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation.
Butyrophilin has been identified in bovine, marine and human (see Taylor et ai., Biochim. Bionhvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Biophys. Acta 1245:285-292 (1995), Mather et ai., J. Dain Sci.
76:3832-3850 (1993), Ogg, et al., Mamm. Genome, 7(12):900-905 (1996), Sato, et al., J. Biochem., I I7(I):147-157 (1995) and Banghart et al., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et al., su ra . Given that butyrophilin plays a role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs.
47. P 1305 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PROI305.
48. PR01273 The lipocalin protein family is a large group of small extracellular proteins.
The family demonstrates great diversity at the sequence level; however, most iipocaiins share characteristic conserved sequence motifs.
Lipocalins are known to be involved in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and as carrier proteins, to act in the general clearance of endogenous and exogenous compounds. Flower, Biochem. J., 318(Pt 1):1-14 (1996); Flower, FEBS Lett., 354(1):7-11 (1994). Thus, novel members of the lipocalin protein. family are of interest.
49. PR01302 CD33 is a cell-surface protein that is a member of the sialoadhesin family of proteins that are capable of mediating sialic-acid dependent binding with distinct specificities for both the type of siaIic acid and its linkage to subterminal sugars. CD33 is specifically expressed in early myeloid and some monocyte cell lineages and has been shown to be strongly associated with various myeloid tumors including, for example, acute non-lymphocytic leukemia (ANLL). As such, CD33 has been suggested as a potential target for the treatment of cancers associated with high level expression of the protein. One CD33 homolog (designated CD33L) is described in Takei et al., CVtOgenet. Cell Genet. 78:295-300 (1997). Another study describes the use of CD33 monoclonal antibodies in bone marrow transplantation far acute myeloid leukemia. Robertson, et al., Proe.
Clin. Biol. Res., 389:47-63 (1994).
Moreover, studies have reported that members of the sialoadhesion family conttybute to a range of macrophage functions, both under normal conditions as well as durUng ixtflammatory reactions. Crocker, et al., Glvcoconi. J., 14(5):601-609 (1997). Moreover, these proteins are aissociated with diverse biological processes, i.e., hemopoiesis, neuronal development and immunity. Kelm, et aL, Glycoconj.
J., 13(6):913-926 (1996).
Thus, novel polypeptides related to CD33 by sequence identity are of interest.
50. PR01283 Olfactory reception occurs via the interaction of odorants with the chemosensory cilia of the olfactory receptor cells located in the nasal epithelium. Based upon the diversity of nasal epithelial-associated odorant binding proteins, the mammalian olfactory system is capable of rea~gnizing and discriminating a large number of different odorant molecules. In this regard, numerous different odorant binding proteins and their encoding DNA have recently been identified and characterized (Dear et al., Biochemistry 30:10376-10382 ( 1991), Pevsner et al., Science 241:336-339 (1988), Buck et al:, Cell 65:175-I87 (/9!91) and Breer et al., J. Recept. Res.13:527 540 (1993)). Because study of the mechanisms of odorant detection by the mammalian olfactory system are of interest, there is significant interest in identifying novel odorant binding protein. We herein describe the identification and characterizationof novel polypeptides having homology to odorant binding proteins, designated herein as PR01283 polypeptides.
51. PR01279 Proteases are enzymatic proteins which are involved in a :large number of very important biological processes in mammalian and non-mammalian organisms. Numerous. different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci., 7(2):5088-5097 (1995) and Chen, et al., J_;Histochem.
Cvtochem., 46:313-320 (1998).
We herein describe the identification and characterization of novel polypeptides having homology to neuropsin protein, designated herein as PR01279 polypeptides.
52. PR01304 The immunophilins are a family of proteins that function as receptors for immunosuppressant drugs, such as cyclosporin A, FK506, and rapamycin. The immunophilins occur in two separate classes, (1) the FK506-binding proteins (FKBPs), which bind to FK506 and rapamycin, and (2) the cyclophilins, which bind to cyciosporin A. With regard to the FK506-binding proteins, it has been reported that the FK5061FKBP
complex functions to inhibit the activity of the serinelthreonine protein phosphatase 2B (calcineurin), thereby providing immunosuppressant activity (Gold, Mol. Neurobiol. 15::?85-306 (1997)). It has also been reported that the FKBP immunophilins are found in the mammalian nervous system and may be involved in axonal regeneration in the cenual nervous system through a mechanism tb~at is independent of the process by which immunosuppression is achieved (Gold, supra). Thus, there is substantial interest in identifying novel polypeptides having homology to the FKBP immunophilins.
We herein describe the identifcation and characterization of novel polypeptides having homology to FK506 binding protein, designated herein as PR01304 polypeptides.
53. PR01317 There is considerable interest in the identification of molecules whose expression is increased upon stimulation of leukocyte populations because insights into the structure and function of these raolecules may lead to further understanding of the intracellular and intercellular events that accompany activation. One such molecule, CD97, a cell surface antigen that is rapidly upregulated upon activation on lymphocytes, has recently been the subject of several publications {see Eichler et al. in Tissue Antigens (199'n x:429-438; Aust et al., Cancer Res. {1997) 57(9):1798-1806). Leukocytes strongly positive for CD97 are concentrated at sites of inflammation relative to CD97 expression in normal lymphoid tissue., A soluble subunit of CD97, CD97alpha, has been found in the body fluids from inflamed tissues {Gray et al. J.
Immunol. (1996) 157!12),:5438-5447}.
54. PR01303 Proteases are enzymatic proteins which are.involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian wo oon2~o8 PCT/US99/20111 protease enzymes play important roles in biological processes such as, for example, protein digestion, activation;
inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocatnpal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., J. Neurosci., 7(2}:5088-5097 (1995} and Chen, et ~~1., J.
Histochem. Cytochem., 46:313-320 (1998). Other studies have reported that kindling induces neuropsin mRNA in the mouse brain. Okabe, et al., Brain Res., 728(I}: I16-120 (I996j. Additionally, a study has reported that generation of reactive oxygen species has an important role in neuropsin transcript in the limbic areas which might be related to the disturbance in avoidance learning. Akita, et al., Brain Res., 769(1):86-96(1997). Thus, neuropsins, and related proteins and agents, including agonists and antagonists are of interest.
55. PR01306 There is much interest in the identification of proteins that play roles in mammalian disease and i5 disorders which could lead to new methods of treatment. A ~atacrophage polypeptide, daintain/alfograft inflammatory factor 1 (daintain/AIFl), has been identified in the pancreas of prediabetic rats, and has been determined to. have a direct effect on insulin secretion. When inyecied intravenously in mice in low doses, daintainIAIFI doses inhibited glucose-stimulated insulin secretion with a concomitant impairment of glucose elimination. At higher doses, daintainlAIFI potentiated glucose-stimulated insulin secretion and enhanced glucose elimination. Thus, it was suggested that daintainlAIFl may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus (Chen et al. _Proc. Nail Acad. Sci. {1997} 94125):13879-13884). AIF-I has also been implicated in both rat and human allogenic heart transplant rejection (Utans et al.
Transplantation (1996) 61(9):1387-1392), and may play a role in macrophage activation and function (Utans et al. J. Clip. Invest. (1995) 95~ø~:2954-2962).
56. PR01336 Protein-protein interactions include receptor and antigen complexes and signalingmechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
Leucine-rich proteins are known to be involved in protein-protein interactions. A study has been reported on leucine-rich proteogIycans which serve as tissue organir~ers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem. Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair ~~re De La Salle, C., et al., Vouv. Rev. Fr.
Hematol. (Germany), 37(4):215-222 ( 1995), reporting mutations in ttae leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome and Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-116 (July 1995), reporting that platelets have leucine rich repeats.
Another protein of particular interest which has been reported to have leucine-rich repeats is the slit protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and S Rothberg, J. M., W09210518-A1 by Yale University. The slit protein has been characterized and reported to be secreted by glial cells and involved in the formation of axonal pathways in Drosophila as well as the mediation of extracellular protein interactions. Wharton and Crews, Mech. Dev., 40(3):141-154 9I993); Rothberg and Artavanis-Tsakonas, J. Mol. Biol., 227(2):367-370 (1992); Rothberg, et al., Genes Dev., 4(12A):2169-2187 {1990); and Rothberg, et al., C~ SS{6):1047-1059 (1988).
57. PROi278 Lysozymes are secretedenzymes that preferentially hydrolyze the [beta]-1,4 glucosidic linkages between N-acetylmuramic acid and N-acetylgucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants.
It has been found in mammalian 1S secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties.
Additional characteristics and possible uses of lysozymes are desct~ibed in U.S. Pat. No. 5,618,712.
5$. P 1298 Glycosylation can determine the fate of a protein, for exatnple, whether it is secreted or not. Also, glycoproteins play many structural and functional roles, particularly as part of the cell membrane: Therefore, glycosylation is of interest. Studies have reported on the growth-related coordinate regulation of the early N-2S glycosylation genes in yeast. Kukuruzinska and Lennon, G_l3rcobioloQV.
4(4):437-443 (1994). Moreover, the relationship between protein glycosylation and fatty acylation of glycoproteins was studied in the wild-type and asparagine-linked glycosylation-deficient mutants in yeast. Appukuttan, FEB
ett., 255(1):139-142 {1989).
The biosynthesis of asparagine-linked oligosaccharides in yeast was also studied using a mutant. Jackson, et al., GlycobiologY, 3(4):357-364 (1993). Yeast mutants deficient in protein.
glycosylation have also been reported in Huffacker and Robbins, PNAS. 80(24):7466-7470 (1983).
59. PR01301 Cytochrome P450 proteins form a large class of rnonooxygenase enzymes involved in hydroxylation.
Hydroxylation reactions are important in the synthesis of cholesterol and steroid hormones. Enzymes of the 3S cytochrome P450 family play an important role in the.metaboiism endogenous compounds such as arachidonic acid. These enzymes are also important in the metabolism of foreign substances such as the elimination of drugs from the body [see, for example, Peterson, Aliment. Pharmacol. Ther., 9:1-9 ( 1995}.]. in addition, metabolites WO 00/I27fl8 PCT/US99/20I 11 generated through the cytochrome P450 pathway may play a role in carcinogenesis, blood pressure regulation and renal function [see, for example, Rahmatt et al., Am. J. Hypertens..
10:356-365 (1997)).
60. PROI268 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01268.
6I. PR01269 Granulocytes, the most common type of white blood cell, have the ability to mediate immunologic cytotoxicity against tumor cells and microorganisms. Accordingly, ~Chere has been interest in identifying various factors that are produced by these cells because of their potential use as pharmaceutical agents. Patent publication no. W09729765-A1, to Selsted, describes the identifit:aaon of granulocyte peptide A which was isolated from bovine and marine granulocytes. Several uses for this peptide were identified including, a therapeutic use, use as an agricultural agent, use as a preservative for food, and use as a water treatment agent.
62. PR01327 Neurexophilin is a protein that was discovered as a neuronal glycoprotein that was copurified with neurexin I alpha during affinity chromatography on immobilized alpha-latrotozin (Missler et al., J. Neurosci.
18:3630-3638 (1998)). Recent data has shown that the mammalian brain contains four genes for neurexophilins the products of which share a common structure composed of five domains: (1) an N-terminal signal peptide, (2) a variable N-terminal domain, (3) a highly conserved central domain that is N-glycosylated, (4) a short linker region and (5) a conserved C-terminal domain that is cysteine-rich (Missler et al., supra). These data further demonstrate that the neurexophilins are proteolytically processed alfter synthesis and bind to alpha-neurexins.
The structure and characteristics of neurexophilins indicate that they may function as neuropeptides that may signal via alpha-neurexins. Therefore, there is significant interest in identifying and characterizing novel polypeptides having homology to the neurexophilins.
We herein describe the identifcation and characterization of novel polypeptides having homology to neurexophilin protein, designated herein as PROi327 polypeptides.
63. 1382 Cere:bellin is a secreted, postsynaptic neuroprotein found throughout the brain. The highest concentrations of this protein have been found in the cerebellum. It has also been detected in the pituitary, spinal cord, and adrenal glands (Satoh et al. J. Endocrinol. (1997) 15491)::27-34).
The feasibility of using cerebellum as a quantifiable marker for the investigation of the maturation of Ptukinje cells of the cerebellum and to chart neurodevelopment has been reported (see Slemmon et al. Proc. Natl. Acad. Sci (1985} 82120):7145-7148).
Significantly decreased levels of cerebellin have been found in human brains obtained in post-mortem studies from patients with spinocerebellar degeneration, olivopontocerebellar atrophy (OPCAQ) and Shy-Drager syndrome, suggesting that cerebellin plays important pathophysiological roles in these cerebellar diseases (Mizuno et al. Brain es. (1995) 686(1):115-118; Mizuno et al. ~Jo To Shinkei (1995} 47(111:1069-1074). In view of the importance of cerebellin in neurodevelopment and tin neurological diseases and disorders, the identification and characterization of members of this protein family is of interest (see also Yiangou et al. J.
Neurochem (1989) 5:886-889 and Mugnaini et al. Swnanse (1988) 2:125-138).
64. PROi328 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01328.
65. PR01325 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane palypeptide designated herein as PR01325.
66. PR01340 Cadherins are known as the principal mediators of hvmotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development.
Cadherins are a diverse family of proteins that have been identified in various tissues including nervous tissue (Suzuki et al., Cell a :, 2:261 270 {199i)). Ksp-cadherin is a kidney-specific member of the cadherin muItigene family (Thomson et al., Biol.
Chem, 2'70:17594-I760I (1995)). Cadherins are thought to play an important role in human cancer {Yap, Cancer Invest., 16:252-261 (1998)).
67. PR01339 Carboxypeptidases are of interest. Carboxypeptidase E a)~pears to be involved in the biosynthesis of a wide range of peptide hormones. Fricker, Annu. Rev. Phvsiol., 50:309-321 (1988). This carboxypeptidase has been associated with obesity. Letter, J. Endo~ol.,155(2):211-214 ( 1997).
Carboxypeptidase M has been reported as being a marker of macrophage maturation. Krause, et: al., Immunol.
Rev.. 161:119-127 (1998).
Human mast cell carboxypeptidase has been reported to be associated with allergies. Goldstein, et al., Monoer.
Allerav, 27: i32-145 (1990). Carbvxypeptidase A2 has also been reported on.
Faming, et al., J. Biol. Chern., 266(36):24606-24612 (1991). Other carboxypeptidases of particulw interest which are known in the art include human pancreatic carboxypeptidase 2, carboxypeptidase al and carb~oxypeptidase B. Therefore; novel members of the carboxypeptidase family are of interest.
68. PR_ 01337 Of particular interest is the identification of blood-reiated proteins which may have potential therapeutic use or may be useful in the diagnosis of blood-related disorders. Thyroxine-binding globulin (TBG). is synthesized by the liver and secreted into the bloodsueam. It is the principal thyroid hormone transport protein in human serum (Refetoff et al. Hotrn. Res. (1996} 4513-S):128-I38}. High serum levels of TBG have been S found to cause hyperthyroxinaemia (Leahy et al., Postgrad Med. J. ( 1984) 60(703):324-327). Accordingly, the identification and characterization of TBG proteins is of interest (see Flink et al. Proc. Natl Acad Sci. USA
(1986) 83(20):7708-7712; Bartalena et al. Acta Med. Austriacaa, (1988} iS
Sup,~l i:12-1S}, including the identification of abnormal TBG proteins (see Refetoff, Endocr Rey. (1989) 10(3):275-293). Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, KIein et al., Proc. Natl. Acad. Sci.. 93:7108-7113 (199fi); U.S.
Patent No. 5,536,637)].
69. PR01342 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and 1S receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences fox novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01342.
70. PR01343 Efforts are being undertaken by bath industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for navel secreted proteins. We herein describe the identif canon and characterization of a novel secreted protein designated herein as PR01343.
2S 7I. PR01480 Semaphorins are a large family of transmembrane and secreted proteins, many of which are expressed in the nervous system. Members of the semaphorin family include both Iigands and receptors. (Eckhardt et al., Mol. Cell. Neurosci.. 9: 409-419 (1997)}. Studies have revealed a role for semaphorins in embryonic motor and central nervous system axon guidance and synapse formation. (Catalano et al., Mol. Cell. Neurosci.. 11:
173-182 (i998); Kitsukawa et al., Neuron, 19: 99S-1005 (I997); Yu et al., Neuron, 20: 207-220 (1998)).
Setnaphorins have been shown to induce neuronal growth cone collapse and alter their pathway in vivo. (Shoji et al., Development, 125: 1275-1283 (1998)). Members of the semaphorin family have been shown to be immunologically active, inducing cytokine production in human monocytes.
(Comeau et al., Immuni , 8_: 473 482 (1998)). Semaphorins may also play a role in cancer. Expression of a mouse semaphorin gene is known 3S to correlate with metastatic ability in mouse tumor cell lines.
(Chriistensen et al., Cancer Res., 58: 1238-1244 (1998)).
WO 00/12708 PC'C/US99/20111 72. PR01487 Fringe is a protein which specifically blacks senate-mediated activation of notch in the dorsal compartment of the Drosophila wing imaginal disc (see Fleming et: al., Development. 124(15):2973-81 (1997);
Wu et al. Science (1996) 273_ 152732355-358). Fringe protein is also involved in vertebrate development where a thickening of the apical ectodermal ridge essential for limb bu<i outgrowth involves an interaction between dorsal cells that express radical fringe and those that do not (see Wolpert, L. Philos Trans R Soc L.ond B Biol ci I998) 353(I370):871-875; Kengaku et al. Science (1998) 280 5( 367):1274-1277; Cohen et al. Nat. Genet:
(1997) 1613):283-288; Johnston et al. Development (1997) 1~11L2245-2254;
Laufer et al. Nature (1997) 386166232_,366-373; Rodriguez-Esteban et al. Nature (1997) 386(66360-366;). ).
Therefore, fringe protein is of interest for both its role in development as .well as its abiliay to regulate serrate, particularly senate's signaling abilities: Also of interest are novel polypeptides which may have a role in development andlor the regulation of serrate-like molecules. Of particular interest are navel polypeptides having homology to fringe protein.
73. PR01418 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recomlbinaut DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01418.
74. 01472 Butyraphilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of buty:rophilin mRNA
has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation.
Butyrophilin has been identified in bovine, murine and human (:gee Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Bioohvs. Acta 1245:28:1-292 (1995), Mother et al., J. Dairy Sci.
76:3832-3850 (1993), Ogg, et al., Mamm. Genome, 7(12):900-905 (1996), Sato, et al., J. Biochem., 117(1):147-157 (1995) and Banghart et at., J. Biol. Chem. 273:4171-4.179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a rate as the principle scaffold for the assembly of a complex witb~ xanthine dehydrogenaseloxidase and other 3fl proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et ai., a a . Given that butyrophilin plays a role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs. Members of the butyrophilin family are further described in Tazi-Ahnini, et at:, Immunog-enetics~ 47(1}:55-63 (1997); Dave;y, et al., Gene. 199(1-2):5?-62 (1997); and Masher and Jack, J. Dairy Sci., 76(12):3832-3850 (1993).
75. PR01461 Proteases are enzymatic proteins which are involved in many biological processes in mammalian and non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide hormone activity, and alteration of the physical properties of proteins and enrymes. Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that hydrolyzes peptide bonds of ingested proteins. Trypsin-like protc;ases have been characterized that are eell-surface proteins (see Farley et al. Biochirn Biophys Acta (1993) 117350-352;
and L.eytus et ad. Biochernistrv (1988) 27(3):1067-1074). It is believed that some of these tryp~sin-like proteins may be synthesized as a membrane-bound precursor which matures to a soluble and active protease (Yamaoka et al. J. Biol. Chem (1998) 273!19):11895-11901).
Because of there importance in metabolism. and other enzynnatic processes, efforts are being undertaken by both industry and academia to identify new, native serine-like proteases.
Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor proteins.
76. PR01410 Efforts are being undertaken by both industry and academia to identify new, native transmernbrane and receptor proteins. Many efforts are focused on the screenirng of mammalian recombinant DNA libraries to identify the coding sequences for novel transrnembrane proteins. We herein describe the identification and characterization of a novel transrnembrane polypeptide designated Therein as PR01410.
77. PR01568 The tetraspanin (or tetraspan) family of proteins has grown to include approximately twenty known genes from various species. The tetraspanins are four transrnembrane: domain membrane-bound molecules which include for example, CDBI, CD82, CD9, CD63, CD37 and CD53. Many of these proteins have a flair for promiscuous associations with other molecules, including lineage-specific proteins, integrins, and other transpanins. In terms of function, they are involved in diverse processes such as cell activation and proliferation, adhesion and motility, differentiation and cancer. One study has proposed that these functions may all relate to their ability to act as "molecular facilitators", grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. Maec1';er, et al., FASEB, 11(6):428-42 (1997).
Another study concludes that they are responsible for changes in cell morphology, cell-ECM adhesion and cell signaling. Skubitz, et al., J. Immunol~ 157:3617-3626 (1996). Thus, new members of this family are of interest.
78. PR01570 Proteases are enzymatic proteins which are involved in many biological processes in mammalian and non-mammalian organisms including digestion, protein activation and inactivation, modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes. Serine proteases comprise a large class of enzymes that exhibit specific activity toward various serine-containing proteins. Trypsin, which is synthesized by the pancreas and secreted to the small intestine, is a well-characterized serine protease that hydrolyzes peptide bonds of ingested proteins. Trypsin-like protnases have been characterized that are cell-surface proteins (see Farley et al. Biochim Biophys Acta ( 1993) 1173,350-352;
and l.eytus et al. Biochemistry (1988) 27(3):1067-1074). It is believed that same of these trypsin-like proteins may be synthesized as a membrane-bound precursor which matures to a soluble and active protease (Yamaoka et al. J. Biol. Chem ( 1998) 273(19):11895-11901).
Of particular interest are human colon carcinoma derived serine proteases SP59, SP60 and SP67 which may be useful to screen for specific inhibitors or modulators to use in treaunent of associated disease states and disorders related to these proteins. In Japanese patent J09i49790-.A, SP60 is reported to be identified, having accession number P W22986 and 233 amino acids.
I O 79. PR01317 Members of the semaphorin family of glycaproteins play important roles in the developing nervous system, and more particularly in axonal guidance. Semaphorins have been identified in the human immune system, where they are believed to play funcrional roles including B-cell signaling (Hall et al. Prac. Natl. Acad.
Sci (1996) 93(21): I 1780-50). A human semaphorin gene, useful in the diagnosis of nervous system an immune I5 disorders, is disclosed in Japanese Pat. No. J10155490-A, published June 16, 1998. The identification of additional members of the semaphorin family if of interest.
80. PR017$0 Enzymatic proteins that may be implicated in metabolic diseases or disorders are of particular interest.
20 The enzymatic addition of sugars to fat-soluble chemicals is an important process that increases their salability in water and aids in their excretion. In mammals, glucuronic acid is the main sugar that is used to prevent the waste products of metabolism and fat-soluble chemicals from reaching toxic levels in the body. The UDP
glucuronosyltransferases that carry out this reaction are part of a super family of UDP glycosyliransferases found in animals, plants and bacteria, In the liver, UDP-glucuronosyltra~nsferase conjugates bilirubin. There are a 25 number of conditions which affect UDP-glucuronosyltransferase activity resulting in unconjugated hyperbilirubinemia. These conditions include genetic disorders such as Crigler-Najjar Syndrome (see Jurgen et al., Biochem. J. (1996) 314:477-483) and Gilbert syndrome, as well as acquired conditions such as Lucey-Driscoll Syndrome. Accordingly, the identification of novel members of the glucuronosyltransferase family is of interest (see Tukey et al., J. Biol. Chem. (1993) 268(20):15260-6; and W09212987-A).
81. 801486 The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping eDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids generally termed precerebellin, or a cerebellin precursor. This protein has a significant similarity to the globular region of the B chain of human complement component Clq. The region of relatedness extends approximately over 145 amino acids located in the carboxyl terminus of both proteins. Unlike CIq B chain, no collagen-like WO 00/I2708 PCTlUS99120111 motifs are present in the amino-terminal regions of precerebellin. It is believed that cerebeIlin is not liberated from precerebellin by the classical dibasic amino acid proteaLytic cleavage mechanism seen in many neuropeptide precursors. The cerebelLin precursor has been associated with synalptic physiology. Urade, et al. , PNAS. USA, 88(3):1069-1073 {1991). Cerebellin, its precursor, and related molecules, particularly those having sequence identity with cerebellin, are therefore of interest.
82. PR-"_ 01433 Efforts are being undertaken by both industry and academia to identify new, native transmembrane and receptor proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane polypeptide designated herein as PR01433.
83. PR01490 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilizaaion of chemical energy, and other processes necessary to sustain life. Acyitransferases are enzymes which acylate moieties. For example, acyl-glycerol-phosphate acyltransferases can act on Iysophosphatidic acid as a substrate.
The Iysophosphatidic acid is converted to phophatidic acid and thus plays a role in forming phosphatidylethanolamine found in membranes.
See, Brown, et al., Plant Mol. Biol., 25(1):211-223 (1994). Moreover, 1-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) is an enzymatic protein that shows a preference for medium-chain-length fatty acyl-coenzyme A substrates. See, Ktlutson et al., Plant Physiol. 109:999-1006 (1995)). Thus, acyltransferases play an important role in the biosynthesis of moIecuIes requiring acylation.
We herein describe the identification and characterization of novel polypeptides having homology to a 1-acyl-sn-glycerol-3-phosphate acyltransferase protein, designated Therein as PR01490 polypeptides.
84. PR01482 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
Libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01482.
85. PR01446 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01446.
WO 00/12708 PCTItJS99/20111 86. PROI558 Methyluansferase enzymes catalyze the transfer of methyl groups from a donor molecule to an acceptor molecule. Methyltransferase enzymes play extremely important roles in a number of different biological processes including, for example, in the electron transport chain in the plasma membrane in prokaryotes and in the inner mitochondria) membrane in eukaryotic cells (see, e.g., Barlkovich et al., J. Biol. Chem. 2?2:9182-9188 S (1997); Dibrov et al., J. Biol. Chem. 272:9175-9181 (1997}, Lee et al., J.
Bacteriol.. 179:1748-1754 (1997) and Marbois et al., Arch. Biochem. Bioph ~~s. 313:83-88 (1994)).
Methyltransferase enzymes have been shown to be essential for the biosynthesis of ubiquinone (coenzyme Q) and.
menaquinone (vitamin K2), both of which are essential isoprenoid quinone components of the respiratory electron transport chain. Given the obvious importance of the methyltransferase enzymes, there is substantial interest in identifying novel polypeptide homologs of the methyltransferases. We herein describe the identification and characterization of a novel polypeptide having homology to methyltransferase enzymes, designated herein as PR01558 polypeptides.
87. PR01604 The identification of novel growth factors is of particular interest because of the roles they play in inducing cellular growth, proliferation and differentiation in both. normal states and abnormal states. The identification of growth factors that are over- or under-expressed in abnormal tissues (e.g. tumors) may lead to the development of diagnostic tools and therapeutic agents. Growth factors have been isolated from hepatoma-derived cell lines. Hepatoma-derived growth factors have been isolated from mouse (Japanese Pat. No.
J09313185-A, published December 9, 1997) and human (Japanese Prat. No.
J06343470-A, published December 20, 1994) tissues. A hepatoma-derived growth factor, isolated from a human hepatoma-derived cell line, has been found to be ubiquitously expressed in several tumor-derived cell lines, as well as in normal tissues (Nakamura et al., J. Biol. Chem (1994) 69 40 :25143-9). The growth factor was determined to be a novel heparin-binding protein that is mitogenic for fibroblasts.
88. PROi491 The neuronal cell body is usually round like any other cell. However, these cells have structures, also referred to as "processes", which grow from them to form synaptic <;onnections. Some of these processes cazry information away from the cell body; sometimes over very long distances. These long and thin processes are axons. The axon is a thin, static tube. Other processes carry information either towards the cell body, or both towards and away from the cell body. These shorter and usually thicker processes are called dendrites. Both axons and dendrites are called neurites.
During development and the growth stage of neurons, neurites are formed by means of growth cones.
A growth cone is the growing tip of a neurite. The growth cone is fllattened and highly motile. It is where new material is added and further extension of the axon originates. Controlling where the growth cone crawls controls were the axon will be laid down and thus where it will be present.
The growth cone has several definable parts. The thin, flattened, veil-like processes that stick out and retract from the leading edge are called lamelIipodia. The needle-like processes that stick out and retract from the leading edge are called microspikes or filopodia. These are the;
structures involved in pushing the leading edge of the growth cone forward.
The accurate navigation of growth cones to their appropriate targets requires that they recognize and respond to navigational cues in their immediate environment. Some of these cues encourage extension into certain areas whereas others discourage extension into others. Well characterized molecules that encourage neurite outgrowth in vitro include the extracellular matrix molecule laminin and the neuronal cell surface molecule Ll/G4/8D9. These molecules which promote neurite extension are generally widely distributed throughout the body. Laminin immunoreactivity is reasonably widespread in the developing central and peripheral nervous systems. Similarly, L1/G418D9 is present on a wide variety of neuronal processes in the developing central nervous system, particularly long projecting axons. II is, therefore, unclear whether the known outgrowth promoting molecules play an important role in self specific choices growth cones make as they decide between possible routes. Instead, their function is believed to provide a generally permissive environment in which growth cones extend and respond to more specific navigational cues.
Among these more specific cues are molecules that inhibit the motility of particular growth cones.
Growth cones have been observed to lose their motile morphology and cease advancing (collapse) on contact with IS other neurites of different types. Territory formation in viuo may mean the manifestation of a process that leads to selective fasciculation in vivo. Some growth cones have been observed to crawl along specific axonal pathways, or stereotype sequences of axonal pathways in developing embryos.
Specific motility inhibiting effects could determine which of several alternative pathways a growth cone will extend on. Growth canes would be expected to prefer growing on axons that do not induce them to collapse while shunning those that do.
It has been observed that, for example, sympathetic growth cones will be inhibited or collapse when coming in contact with retinal neurites. Likewise, growth cones of retinal neurites will collapse when coming in contact with sympathetic neurites. It is believed that such cell activity is achieved through the presence of receptors which specifically respond to specific growth inhibition cues by the molecules which transmit specific cues pertaining to growth. Cues are believed to be present on cell surfaces, particularly on axon surfaces.
When nerve damage occurs, repair is impeded or incapable of occurring due to the failure of neurites to replace damaged axons or dendrites. If an existing neurite is damaged, severed or destroyed, a new neurite is incapable of growing out from the cell body to replace it. The F~resence of molecules which inhibit neurite growth are believed to be responsible for the difficulty in neurite :regeneration. Collapsins are proteins that function to modulate the activity of molecules which modulate growth cone extension.
We herein describe the identification and characterization of novel polypepddes having homology to a collapsin protein, designated herein as PR01491 polypeptides.
89. PR01431 The transduction of intracellular signaling is crucial to cell processing such as differentiation, motility and division. Such signal transduction is believed to occur throughout the cell in the form of complex interactions between proteins. Such protein-protein interactions are often mediated by modular domains within signaling proteins. As a result, signal transduction is now modeled as a system in which molecules act in a combination, and the composition of that combination, determines the signal.
Src homology domains (e.g., SH2 and SH3) are two domains found in regions of sequence similarity of proteins involved in signal transduction. Early work on the oncogenic tyrosine kinase Src identified the SH2 domain. Since then, SH2 and SH3 domains have been found in many diverse proteins, making them among the most common type of structural motif. SH2 and SH3 domains are modular in that they fold independently of the protein that contains them, their secondary structure places N- and C-termini close to one another in space, and they appear at variable locations (anywhere from N- to C-terminal) from one protein of the next (Cohen et al., Cell 80: 237-348, 1995).
Early studies that mutated the SH2 or SH3 domain showedL that these two domains were important for function, but it was not until the cloning of unrelated families of signaling proteins such as RAS-GAP, and the Crk oncogene that the modular nature of these domains was revealed. These tatter experiments demonstrated that RAS-GAP and Crk bound tightly to receptor tyrosine kinases upon ligand stimulation. Follow-up studies demonstrated that the mechanism of this binding was through the SH2 domain and that receptor autophosphorylation was required. Such a fording implied that activation of the receptor tyrosine kinase could be viewed as a means of changing the binding aspect of the inuacellular domain, and the receptor-SH2 containing protein interaction would initiate the signal transduction cascade.
SH3 domains have a more general function than that which its purported for SH2. SH3 binding proteins have been isolated by screening bacteriophage expression libraries with labeled SH3 domains. The results of these experiments showed that SH3 domains would bind to short proline-rich peptides, in particular the motif PxxP. Based on the level of knowledge present at the time of the preparation of the present patent application, all of the SH3 binding sites identified have the property of being proline rich. Binding of an SH3 domain is independent of covalent modification of the binding site, such as phosphorylation as occurs with the SH2 domain.
As a result, SH3-ligand interactions are usually constitutive and not iLnducible, although exceptions do exist. In general, SH3 domains are less likely to act as signal "switches" than as a means of assembling protein complexes via moderate-affinity interactions. Such moderate affmiry interactions also imply that the SH3-mediated interactions will be relatively short in duration and remodeled in response to changes in concentration of binding partners.
The resolution of binding characteristics of SH2 and SH3 domains has led to proposed compounds which would block signal transduction. Peptidomimetic Iigands based on the sequence of target proteins for SH2 and SH3 domains may represent new lead compounds for the therapy of proliferative diseases that are dependent upon constitutively activated tyrosine kinases (e.g., BCR/ABL in chronic myelogenous and acute lymphocytic leukemias or HER-2/Neu in breast and ovarian cancer).
90. PR01563 Cellular disintegrin and mtaalloproteinase (ADAMS) are a :family of genes with a sequence similar to those of snake venom metalloproteinases and disintegrins. The ADAMTS-1 gene encodes a new type of ADAM
protein with respect to possessing the thrombospondin (TSP) type I motifs, the expression of which is associated with the inflammatory process (Kuno et al., J. Biol. Chem. 273:13912-13917 (1998), Kuno et al., Genomics 46:466-471 (1997) and Kuno et al., J. Biol. Chem. 272:556-562 (1!97)).
Expression of the ADAMTS-1 gene is induced in kidney and heart by in vivo administration of lipopolysaccharide, suggesting a possible role in the inflammation reaction. In this regard, the ADAMTS-1 protein has been suggested as playing a possible role in various inflammatory processes as well as in the development of cancer cachexia (Kuno et al., 1998, supra).
We herein describe the identification and characterization of novel pollypeptides having homology to ADAMTS-1 protein, designated herein as PR01563 polypeptides.
91. PR01565 Chondromodulin proteins are cartilage-generated matrix components that synergistically stimulate the growth and differentiation of chondrocytes (Suzuki, Connect. Tissue Res.
35:303-307 (1996)). More specifically, chondromodulin-1 functions to inhibit the proliferation of vascular endothelial cells and tube formation, thereby functioning to stimulate cartilage growth and inhibiting replacing cartilage by bone in an early stage. Chondromodulin-II, while not capable of inhibiting vascularization like chondromodulin-I, also functions to stimulate osteoclast differentiation and cartilage growth. As such, these two polypeptides are essential for the regulation of the formation of cartilage and endochondral bone structures.
Given the extremely important physiological roles played by the chondromodulin proteins, there is significant interest in identifying and characterizing novel polypeptides having homology to these proteins, We herein describe the identification and characterization of novel polypeptides having homology to chondromodulin-I
protein, designated herein as PR01565 polypeptides.
92. PR01571 Clostridium perfringens enterotoain (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food poisoning and may also be involved in other human and veterinary illnesses (McCiane, Toxicon. 34:1335-1343 (1996)). CP~E carries out its adverse cellular functions by binding to an approximately 50 kD cell surface receptor protein designated the Clostridium perfringens enterotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. cDNAs encoding the CPE-R protein have been identified characterized in both human and mouse (Katahira et al., J. Cell Biol. 136:1239-1247 (1997) and Katahira et al., J. Biol. Chem. 272:26652-26658 (1997)). Since the CPE toxin has been reported to cause a variety of illnesses in mammalian hosts and those illnesses are initiated by binding of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PR01679 polypeptides.
93. PR01572 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs-showing homology to the Clostridium enterotoxin receptor (CPE-R) gene have previously been cloned as described in Katahira, et al., 1. Biol.
Chem., 272(42):26652-8 (1997).
They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal ai apoptosis protein (RVP1). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.
Also of interest are members ofthe claudin family and molecules related thereto. Claudins are integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. Furuse, et al., J. Cell Biol., 14I(7}:1539-50 (I998).
94. PROi573 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs showing homology to the Clostridium enterotoxin receptor (CPE-R) gene have previously been cloned as described in Katahira, et al., J. Biol.
Chem., 272(42):26652-8 (1997).
They have been classified into two groups, the Vero cell CPE receptor homologies and rat androgen withdrawal apoptosis protein (RVPl). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.
Also of interest is the ventral prostate.l protein (RVP.1) which is transcriptionally induced in the regressing rat prostate after castration. This protein is further described in Peacock, et al., Genomics:
46(3):443-9 (I997).
95. PR01488 Clostridium perfringens enterotoxin utilizes two structurally related membrane proteins as functional receptors in vivo. Human and mouse cDNAs showing homoloF,ry to the Clostridium enterotoxin recegtor (CPE-R) gene have previously been cloned as described in Katahh~a, et al.; J.
Biol. Chem., 272(42):26652-8 (1997), and Katahira, et al., J. Cell Biol., 136(6):1239-1247 (I997). They have been classified into two groups, the Vero cell CPE receptor homologues and rat androgen withdrawal apoptosis protein (RVPl). These receptors are thus of interest as are related molecules. Of particular interest is the use of these receptors and related molecules in the identification of modulators of these receptors.
Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for-novel receptor proteins.
96. PR01489 Clostridium perfringens enterotoxin (CPE) is considered to be the virulence factor responsible for causing the symptoms of C. perfringens type A food. poisoning and may also be involved in other human and veterinary illnesses (McClane, Toxicon. 34:1335-1343 (1996)). Cl'E carries out its adverse cellular functions by binding to an approxinnately 50 kD cell surface receptor protein designated the Clostridium .perfringens enierotoxin receptor (CPE-R) to form an approximately 90,000 kD complex on the surface of the cell. eDNAs encoding the CPE-R protein have been identified characterized in both human and mouse (Katahira et al., J. Cell Biol. 136:1239-1247 (1997) and Katahira et al., J. Biol. Chem. 272:26652-26658 (1997)). Since the CPE toxin _ has been reported to cause a variety of illnesses in mammalian, hosts and those illnesses are initiated by binding ii of the CPE toxin to the CPE-R, there is significant interest in identifying novel CPE-R homologs. We herein describe the identification and characterization of novel polypeptides having homology to the CPE-R, designated herein as PR01489 polypeptides.
97. PR01474 Avian egg whites are a rich source of protein inhibitors of I>roteinases belonging to all four mechanistic classes. Ovomucoid and ovoinhibitor are muitidomain ICazal-type inhibitors with each domain containing an actual or putative reactive site for a serine proteinase. Cystatin is a cysteine proteinase inhibitor, while ovostatin inhibits proteinases of all four mechanistic classes. For a review of these inhibitors, see Saxena and Tayyab, Cell Mol. Life Sci., 53(1):13-23 (1997). New members of protein inhibitors of prnteinases are Qf interest, particularly those having sequence identity with known inhibitors such as ovomucoid.
Serine protease inhibitors in general are of interest. Serine proteases such as neuropsin have been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci., 7{2):5088-5097 (1995) and Chen, et al., J. Histochem. Cvtochem., 46:313-320 (1998): Another serine protease, the enamel matrix serine proteinase, is associated with the degradation of organic matrix in teeth.
Simmer, et al., J. Dent. Res., 77(2):377-386 (1998), Overall anal Limeback, Biochem J., 256{3):965-972 {1988), and Moradian-Oldak, Connect. Tissue Res., 35(1-4):231-23.8 (1996).
Thus, inhibitors of these proteases are of interest in the case that these mechanisms require control.
98. PR01508 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the idE;ntilication and characterization of a novel secreted protein designated herein as PR01508.
99. PROIS55 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PRO1555.
i00. PR01485 Lysozymes are secreted enzymes thatpreferentiallyhydrolyxethe [beta]-1,4 glucosidic linkages between N-acetylmuramic acid and N-acetyigucosamine which occur in the mucopeptide cell wall structure of certain microoganisms. Lysozyme is of widespread distribution in animals and plants:
It has been found in mammalian secretions and tissues including saliva, tears, milk, cervical mucus, leucocytes, kidneys, etc. The identification of new members of the lysozyme family of proteins is of interest because of the variety of roles lysozymes play in metabolic function and dysfunction. Abnormal levels of lysozymes have been implicated in various disease states. Lysozymes have been reported to have anti-microbial, analgesic, and antinociceptive properties.
Additional characteristics and possible uses of lysozymes are described in U.S. Pat. No. 5,618,712.
Of particular interest is Iysozyme C which has been recruited as a digestive enzyme in the stomachs of creatures needing to retrieve nutrients from microorganisms in fermented food.
The history of lysozyme C and related proteins are further described in Qasba and Kumar, Crit. Rev. Biochem.
Mol. Biol., 32(4):255-306 (1997); Irwin, EXS. 75:347-361 (1996) 10I. PR01564 Glycosylation is a common and complex form of post-transiational protein modification. Although a large and increasing number of unique structures is ~Irnown to exist, most arise from a series of common synthetic intermediates and differ at their periphery glycosyltransferases, which recognize both the oligosaccharide acceptor and features of the underlying protein. UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase is an enzymatic protein that initiates O-glycosylation of specific serine and threonine amino acids in proteins by adding N-acetylgalactosamine to the hydroxy group of these amino acids.
Since numerous important biological and physiological events are regulted by protein glycosylation, there is significant interest in identifying and characterizing novel poiypeptides having homology to the known glycosylation proteins. We herein describe the ident~cation and characterization of novel polypeptides having homology to an N-acetylgalactosaminyitransferase protein, designated herein as PR01564 polypeptides.
102. PR017S5 Efforts are being undertaken by both industry and acadennia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian. recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01755.
103. PRO 757 Efforts are being undertaken by both industry and acadeutia to identify new, native transtnembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01757.
104. PR01758 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01758.
105. PR01575 Protein Disulfide Isomerase (PDI) enhances formation of disulfide bonds in human serum albumin (HSA). Consequently, PDI assists in the formation of the overall structure of human serum albumin. Co-expression of PDI with human serum albumin increases secretiion of HSA by reducing the chance of HSA
structural instability and destruction by cellular proteases. Co-expression of PDI and HSA improved localization in the endoplasmic reticulum of eukaryotic cells. (Hayano et al., E;P-50941-A
( 1992)). PDi and the beta-subunit of human prolyl 4-hydroxylase have been shown to be products of the same gene.
(Pihlajaniemi et al., EMBO
J., 6:b43-49 (1987)). In addition, copies of the CGHC-containing active site sequences of PDI have been found in an abundant luminal endopIasmic reticulum protein, Erp72. (Mfazzarella et al., J. Biol. Chem., 2:1094-1 IOI
(1990)).
ld Efforts are being undertaken by both industry and academia to identify new, natiive receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins.
106. PR01787 Multiple de novo MPZ (PO) point mutations have been id'.entified in a sporadic Dejerine-Sottas (DDS) case. Warner, et al., Hum. Mutat., 10(1):21-4 (1997). DDS is a severe demyelinating peripheral neuropathy with onset in infancy, and has been associated with mutations in either PMP22 or MPZ. Moreover, mutational analysis of the MPZ, PMP22 and Cx32 genes in patients of Spanish ancestry with Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies have been reported on. Bort, et al. , Hum. Genet. , 99(6):746-54 (1997). Myelin giycoprotein PO has been reported on in a number of other studies as well (Blanquet-Grossard, et al., Clin. Genet., 48(6):281-3 (1995), Hayasaka, et al., Nat. Genet., 5(1}:31-4 (1993) and Saavedra, et al., J. Mol. Evol., 29(2):149-56 (1989). Thus, proteins which may belong to the myelin p0 family are of interest.
107. PR01781 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01781.
108. PR01556 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PR01556.
109. PROI759 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein d!.escribe the identification and characterization of a novel transmembrane protein designated herein as PR01759.
110. PR01760 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PR01760.
111. PROI561 Phospholipase A2 (PLA2) is a protein which hydrolyzes a 2-acyl ester bond of phospholipids, and examples thereof include cytosolic PLA2 and secretory PLA2 which can be clearly distinguished from each other. It has been known that the cytosoIic PLA2 (cFLA2) selectively hydrolyzes phospholipids containing arachidonic acid of which 2-position is esterified. Given these important biological activities, there is significant interest in identifying and characterizing novel plypeptides having homology to phospholipase A2 proteins. We herein describe the identification and characterization of novel polypeptides having homology to human phospholipase A2 protein, designated herein as PR01561 polypeptides.
112. PR 1567 Colon specific genes (CSGs)and their expression products are described in published international application W09639419. They are useful diagnostic markers for colon cancer and for colon cancer metastasis and can also be used to screen for potential pharmaceutical and diagnostic agents. The identification of new members of the CSG family is of interest.
113. PR01693 Insulin-like growth factors have both growth-promoting and insulin-like activities. There are two well characterized plasma IGF-binding proteins in human. The larger protein is an acid-labile protein of 53K which circulates mostly as a 125 to 150 kD complex thought to be composed of IGF-I
or IGF-II, the binding protein itself and an acid-labile non-IGF-binding protein with an approximate molecular mass of 10(1K kD. The smaller protein has an apparent molecular mass of 28K in the non-reduced form and 34K
when reduced. These IGF-binding proteins have been shown to play important roles in the physiological activities played by the insulin-like growth factor proteins. As such, there is substantial interest irt identifying and characterizing novel polypeptides 3S having homology to the insulin-like growth factor binding proteins. We herein describe the identification and characterization of novel polypeptides having homology to an insulin_like growth factor binding protein, designated herein as PROI693 polypeptides.
114. PR01784 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transrnembrane protein designated herein as PR01784.
115. PR01605 N-acetylglucosaminyltransferase proteins comprise a fancily of enzymes that provide for a variety of important biological functions in the mammalian organism. As an example, UDP-N-acetylglucosamine: alpha-3-D-mannoside beat-I,2-N-acetylglucosaminyltransferase I is an enzymatic protein that catalyzes an essential first step in the conversion of high-mannose N-glycans to hybrid and complex N-glycans (Sarkar et al., Proc. Nati.
Acad. Sci. USA. 88:234-238 (1991). Given the obvious importance of the N-acetyIglucosaminyltransferase enzymes, there is significant interest in the identification and characterization of novel golypeptides having homology to an N-acetylglucosaminyltransferase protein. We herein describe the identification and characterization . of novel polypeptides having homology to m N-acetylglucosaminyltransferase protein, designated herein as PR01605 polypeptides.
116. PR01788 Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
Proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number o~f proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arrangedl so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglobular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci. 19(10):415-421 (Oct. 1994).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 {1997). Others studies implicating leucine rich proteins in wound healing and tissue repair have been reported including De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome;
Chlemetson, K. J., Thromb. Haemost. (Germany), 74(1):111-llli (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al.; and W09110727-A. by La Jolla Cancer Research Foundation, reporting that decorin binding to transforming growth factor-a has involvement in a ueatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo. Ollendorff, V., et al., ~e:ll Growth Differ, 5(2):213-219. (Feb. 1994) identified the CARP gene which encodes a leucine-rich repeat-containing protein that has structural similarities with human GP Ib alpha and GP V platelet proteins, and with the Chaoptin, Toll, and Connectin adhesion molecules of Drosophila.
Another protein which has been reported to have leucine-rich repeats is the SLiT protein which has been IO reported to be useful in treating neurodegenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-Ai by Yale University. Of particular interest is LIG-:l , a membrane giycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich re~ats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. CeII
Endocrinol., (Ireland), I25(i-2):65-70 (Dec. 1996) (gonadotrapin receptor involvement); Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J.
Am. Soc. Neph_~ol., 6(4):1 I25-1 I33 (Oct. 1995) (kidney disease involveraent); and Almeida, A., et al., Onco ene 16(23):2997-3002 (lone 1998) (malignant glioma involvement).
117. PR01801 Interleukin-10 (IL-10) is a pleiotropic immunosuppressiv~e cytokine that has been implicated as an important regulator of the functions of myeloid and lymphoid cells. It has been demonstrated that IL-10 functions as a potent inhibitor of the activation of the synthesis of various inflammatory cytokines including, for example, IL-i; IL-6, TFN-y and TNF-a (Lesser et al., Proc. Natl, Acad. Sci.
USA 94:14620-14625 (1997)).
Moreover, IL.-IO has been demonstrated to strongly inhibit several of the accessory activities of macrophages, thereby functioning as a potent suppressor of the effector functions of macrophages, T-cells and NK cells (Kahn et al., Cell 75:263-274 (1993)). Furthermore, IL-10 has been strongly implicated in the.regulation of B-cell, mast cell and thymocyte differentiation.
34 IL-10 was independently identified in two separate lines of experiments.
First, cDNA clones encoding marine IL-10 were identified based upon the expression of cytokine synthesis inhibitory factor (Moore et al., Science 248:1230-1234 (I990)), wherein the human IL-10 counterpart cDNAs were subsequently identified by cross-hybridization with the marine IL-10 cDNA (Viera et al., froc. Natl.
Acad. Sci: USA 88:1172-1176 (i991)). Additionally, IL-10 was independently identified as a B-cell-derived mediator which functioned to co-stimulate active thymocytes (Suds et al., Cell Immunol, 129:228 (1990)).
Recently, a novel cytokine polypeptide which is member of the IL-10-related cytokine family has been identified and characterized. This novel secreted cytokine, designated IL-19, is a 177 amino acid polypeptide WO 00/12708 PCT1US99/201 I i having a molecular weight of approximately 20.41cD (see WO 98/08870, published March S, 1998). It has been reported that IL-19 is specifically expressed by activated monocytes, wherein increased andlor decreased levels of IL-19 may be associated with one or more physiological disorders that are associated with increased or decreased levels of cytoltine production (see WO 98/08870). Specifically, IL-19 is suggested as being capable of inhibiting the synthesis of inflammatory cytolcines by cells of tine immune system.
Given the obvious importance of the various cytolcine polypeptides and, more specifically, immunosuppressive cytokines such as IL-10 and potentially IL-19, there is significant interest in the identification and characterization of novel cytolcine polypeptides having homology to IL-10 and/or IL-19. We herein describe the identification and characterization of novel polypeptides having homology to IL-19, designated herein as PR01801 poiypeptides.
118. UCP4 Uncoupling proteins or "UCPs", believed to play a role in the metabolic process, have been reported in the literature. UCPs were first found and described in the brown fat cells of hibernating animals, such as bears. UCPs were believed to help such hibernators and other cold-weather adapted animals maintain core body 1S temperatures in cold weather by raising their body's resting metabolic rate. Because humans possess relatively small quantities of brown adipose tissue, UCPs were originally thought to play a minoi role in human metabolism.
Several different human uncoupling proteins have now been described. [See, generally, Gura, Science, 280:1369-1370 (1998)]. The human uncoupling protein referred to as UCPl was identified by NicholIs et al.
Nicholls et al. showed that the inner membrane of brown fat cell mitochondria was very permeable to proteins, and the investigators traced the observed permeability to a protein, called UCP 1, in the mitochondrial membrane.
Nicholls et al. reported that the UCPl, by creating such permeability, reduced the number of ATPs that can be made from a food source, thus raising body metabolic rate and generating heat.
[Nicholls et al., Physiol. Rev., 64, 1-64 (1984)].
ZS It was later found that UCPl is indeed expressed only in brown adipose tissue [Bouillaud et al., Proc.
Natl. Acad. Sci., 82:445-448 (1985); Jacobsson et al., J. Biol. Ci~em., 260:16250-16254 (1985)]. Genetic mapping studies have shown that the human UCPl gene is located an chromosome 4: [Cassard et al., J. Cell.
Biochem., 43:255-264 (1990)].
Another human UCP, referred to as UCPH or UCP2, has also been described.
[Gimeno et al., Diabetes, 46:900-906 (1997); Fleury et at., Nat. Genet., 15:269-272 (1997); Boss et al., FEBS Letters, 408:39-42 (1997);
see also, Wolf; Nutr. Rev. , 55:178-179 (1997)]. Fleury et al. teach that the UCP2 protein has 59% amino acid identity to UCPl, and that UCP2 maps to regions of human chromosome 11 which have been linked to hyperinsulinaemia and obesity. [Fleury et al.; supra]. ~It has also been reported that UCP2 is expressed in a variety of adult tissues, such as brain and muscle and fat cells. [Gimeno et al., supra, and Fleury et al., supraj.
3S A third human UCP, UCP3, was recently described in Boss et al., supra;
Vidal-Puig et al., Biochem.
Biophys. Res. Comm., 235:79-82 (1997); Solanes et al., J. Biol. Chem., 272:25433-25436 (1997); and Gong et al., J. liiol. Chem., 272:24129-24132 (1997). [See also Great Britain Patent No. 9716886j. Solanes et al.
report that unlike UCPl and UCP2, UCP3 is expressed preferentially in human skeletal muscle, and that the UCP3 gene maps to human chromosome 11, adjacent to the UCP2 gene. [Solanes et al., supra]. Gong ei al.
describe that the UCP3 expression can be regulated by known the:rmogenic stimuli, such as thyroid hormone, beta3-andrenergie agonists and leptin. [Gong et al., supra].
119. PR0193 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of a novel transmembrane protein designated herein as PROI93.
120. PRO11 0 PoIypeptides such as the human 2-19 protein may function as cytokines.
Cytokines are low molecular weight proteins which function to stimulate or inhibit the differentiation, proliferation or function of immune cells. Cytokine proteins often act as intercellular messengers and have multiple physiological effects. Given the physiological importance of immune mechanisms in vivo, efforts are currently being undertaken to identify new, native proteins which are involved in effecting the immune system. We describe herein the identification of a novel polypeptide which has sequence similarity to the human 2-19 protein.
121. PROl 35 Carbonic anhydrase is an enzymatic protein that which aids carbon dioxide transport and release in the mammalian blood system by catalyzing the synthesis (and the dehydration) of carbonic acid from (and to) carbon dioxide and water. Thus, the actions of carbonic anhydrase are essential for a variety of important physiological reactions in the mammal. As such, there is significant interest in the identification and characterization of novel polypeptides having homology to carbonic anhydrase. We herein describe the identification and characterization of novel polypeptides having homology to carbonic anhydrase, designated herein as PR01335 polypeptides.
122. R 329 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many efforts are focused on ttte screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRC11329.
123. PR01550 Efforts are being undertaken by both industry and academia to identify new, native secretexl proteins.
Many efforts are focused on the screening of mammalian recombiinant DNA
libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of a novel secreted protein designated herein as PRO1550.
SUMMARY OF THE INVENTION
1. PR 1 60 A cDNA clone (DNA19902-1669) has been identified that encodes a novel polypeptide believed to be a novel member of the tetraspan family, designated in the present application as "PR01560."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01560 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA yaving at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01560 polypeptide having the sequence of amino acid residues from 1 or about 43 to about 245, inclusive of Figure 2 {SEQ ID N0:4), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01560 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 167 and about 775, inclusive, of Figure 1 (SEQ ID N0:3). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 %.
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203454 (DNA19902-1669), or (b) the complement of the DNA molecule of {a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No: 203454 (DNA19902-1669).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID N0:4), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01560 polypeptide having the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID N0:4); or (b) the complement of the DNA molecule of (a), and, if the DNA molecule Jitas at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably 2~t least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01560 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 42 in the sequence of Figure 2 (SEQ ID
N0:4). The transmembrane domains have been tentatively identified as at about amino acid positions 19-42, 61-83, 92-114 and 209-230 in the PR01560 amino acid sequence (Figure 2, SEQ ID N0:4).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a pofypeptide scoring at least about 80% positives, preferably at least about 8S% positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID N0:4), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01560 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1PR01560 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1560 poIypeptide, which in one 1 S embodiment, includes an amino acid sequence comprising residues l or about 43 through 245 of Figure 2 (SEQ
ID N0:4).
In another aspect, the invention concerns an isolated PR01560 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID NO:4).
In a further aspect, the invention concerns an isolated PR01560 poiypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives v~rhen compared with the amino acid sequence of residues 1 or about 43 through 245 of Figure 2 (SEQ ID N0:4).
In yet another aspect, the invention concerns an isolated PR0156(?
polypeptide, comprising the sequence of amino acid residues i or about 43 to about 245, inclusive of Figure 2 (SEQ
ID N0:4), or a fragment thereof sufficient to provide a binding site for an anti-PR01560 antibody. Preferably, the PROI560 fragment retains a qualitative biological activity of a native PR01560 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01560 polypeptide having the sequence of amino acid residues from about 1 or about 43 to about 245, inclusive of Figure 2 (SEQ ID N0:4), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01560 WO 00112708 PCT/US99/ZOlll polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01560 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01560 polypeptide, by contacting the native PR0156() polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a cornposition comprising a PR01560 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
2. PR0444 A cDNA clone (DNA26846-1393) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0444:"
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA ;having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA moie,cule encoding a PR0444 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID
N0:6), or (b} the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0444 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 656 and about 958, inclusive, of Figure 3 (SEQ ID NO:S}. Preferably, hybridization occurs under stringent hybridization anct wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 io sequence identity, more preferably at least about 90 % sequence identity; most preferably at Least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203406 (DNA26846-1397), or (b) the complement of the DNA molecule of (a). .In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203406 (DNA26846-1397).
In a still further aspect, the invention concerns an isolated. nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about l or about 17 to about 117, inclusive of Figure 4 (SEQ ID N0:6), or the complement of the DNA of (a).
In a further aspect; the invention concerns an isolated nucleic acid molecule having at least about 10 nucleotides, more preferably at least about 20 nucleotides, and most preferably at least about 40 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0444 poIypeptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0444 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 16 in the sequence of Figure 4 (SEQ
1D N0:6).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0444 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are froth about 20 to about 80 nucleotides in length, IS preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0444 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0444 polypeptide, which in one embodiment, includes an amino acid sequence comprising residue,. 1 or about 17 to 117 of Figure 4 (SEQ ID
N0:6).
In another aspect, the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID N0:6).
In a further aspect, the invention concerns an isolated PR0444 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 17 to l I7 of Figure 4 (SEQ TD N0:6).
In yet another aspect, the invention concerns an isolated PRO444 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 117, inclusive of Figure 4 (SEQ
ID N0:6), or a fragment thereof sufficient to provide a binding site for an anti-PR0444 antibody. Preferably, the PR0444 fragment retains a qualitative biological activity of a native PR0444 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0444 polypt;ptide having the sequence of amino acid residues from about 1 or about 17 to about 117, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 %a sequence identity to {a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable l;or expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
3. PR01018 A cDNA clone (DNA56107-1415) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01018".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01018 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 84%a sequence identity, preferably at least about 85% sequence identity; more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01018 polypepiide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID
N0:8), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01018 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 129 or about 201 and about 695, inclusive, of Figure S (SEQ ID N0:7). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85',~o sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95'~o sequence identity to {a) a DNA molecule encoding the same maitue polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203405 (DNA56I07-1415) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203405 (DNA56107-1415).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, nnost preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure62 (SEQ ID
N0:8), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least lU
nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01018 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01018 polypegtide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 6 (SEQ ID
N0:8). The transmembrane domains have been tentatively identified as extending from about amino acid position 86 to about amino acid position 103 and from about amino acid position 60 to about amino acid position 75 in the PROI018 amino acid sequence (Figure 6, SEQ ID N0:8).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polygeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 10118 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, IS preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 5 (SEQ ID N0:7).
In another embodiment, the invention provides isolated PR01018 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01018 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 189 of Figure 6 {SEQ ID N0:8).
In another aspect, the invention concerns an isolated PR01018 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably .at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID N0:8).
In a further aspect, the invention concerns, an isolated PRO )<018 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID N0:8}.
In yet another aspect, the invention concerns an isolated PRO 1018 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 189, inclusive of Figure 6 (SEQ
ID N0:8), or a fragment thereof sufficient to provide a binding site for an anti-PROI018 antibody. Preferably, the PR01018 fragment retains a qualitative biological activity of a native PRO1018 polypeptide.
In a still further aspect, the invention provides a polypepiide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01018 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 189, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
4. PR01773 A cDNA clone (DNA56406-1704} has been identified, having homology to nucleic acid encoding a retinol dehydrogenase protein that encodes a novel polypeptide, designated in the present application as "PR01773".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01773 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1773 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID
NO:10), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01773 polypeptide comprising DNA hybridizing to the complement of thc; nucleic acid between about nucleotides 111 or about 162 and about 1067, inclusive, of Figure 7 (SEQ ID N0:9). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 ~o sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203478 (DNA56406-1704) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC Deposit No. 203478 {DNA56406-1704).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at Least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 3I9, inclusive of Figure 8 (SEQ ID
N0:10), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 525 nucleotides and produced by hybridizing a test DNA molecule mnder stringent conditions with (a) a DNA
molecule encoding a PR01773 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID N0:10), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 8S % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01773 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position I7 in the sequence of Figure 8 (SEQ ID
NO:10). The transmernbrane domain has been tentatively identified as extending from about amino acid position 136 to about amino acid position 152 in the PR01773 amino acid sequence (Figure 8, SEQ ID NO:10).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at Ieast about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 18 to about 319, inclusive of Figure 8 {SEQ ID NO:10), or (b) the complement of the DNA of (a).
Another.embodiment is directed to fragments of a PROI7 73 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about X40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 7 (SEQ ID N0:9).
In another embodiment, the invention provides isolated PR01773 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native; sequence PR01773 polypeptide,, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 3I9 of Figure 8 (SEQ ID NO:10).
In another aspect, the invention concerns an isolated PR01.773 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at Ieast about 9S% sequence identity to the sequence of amino acid residues 1 or about 18 to about 319, inclusive of Figure 8 {SEQ ID NO:10).
In a further aspect, the invention concerns an isolated PR01773 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about I8 to about 319, inclusive of Figure 8 (SEQ ID NO:10).
In yet another aspect, the invention concerns an isolated PRO 1773 polypeptide, comprising the sequence of amino acid residues I or about 18 to about 319, inclusive of Figure 8 (SEQ
ID NO:10), or a fragment thereof sufficient to provide a binding site for an anti-PR01773 antibody. Preferably, the PROI773 fragment retains a qualitative biological activity of a native PR01773 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by {i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01773 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 319, inclusive of Figure 8 (SEQ ID NO:10), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poIypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PROI773 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01773 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROi773 polypeptide by contacting the native PROI773 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1773 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
5. PR01477 IS A cDNA clone (DNA56529-1647) has been identified, having homology to nucleic acid encoding a mannosidase protein that encodes a novel polypeptide, designated in the present application as "PR01477".
In one embadiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01477 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1477 polypeptide having the sequence of amino acid residues from about i to about 699, inclusive of Figure 10 (SEQ ID N0:12), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01477 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 23 and about 2119, inclusive, of Figure 9 (SEQ ID NO:11). Preferably, hybridization occurs under stringent hybridization and wash conditions In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85%'~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203293 (DNA56529-1647) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203293 (DNA56529-1647).
In still a further aspect,. the invention concerns an isolated. nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence WO OO/I2708 PCTIUS99IZOi11 identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID N0:12), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 540 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (af a DNA
molecule encoding a PR01477 polypeptide having the sequence of amino acid residues from 1 to about 699, inclusive of Figure 10 (SEQ ID N0:12), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01477 polypeptide, with or without andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants; or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extendvng from about amino acid position 21 to about amino acid position 40 and from about amino acid position 84 to about amino acid position 105 in the PR01477 amino acid sequence (Figure I0, SEQ ID N0:12).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide scoring at least about 80% positives, prE;ferabIy at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure 10 (SEQ ID
NO: I2), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1477 poiypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are fmnn about 20 to about 80 nucieotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 9 (SEQ ID NO:11).
In another embodiment, the invention provides isolated fR01477 polypeptide encoded by acry of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01477 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 699 of Figure 10 (SEQ
ID N0:12).
In another aspect, the invention concerns an isolated PR01477 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SEQ ID
N0:12}.
In a further. aspect, the invention concerns an isolated PR01477 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 699, inclusive of Figure IO (SEQ ID NO:I2;).
In yet another aspect, the invention concerns an isolated PR01477 polypeptide, comprising the sequence of amino acid residues 1 to about 699, inclusive of Figure 10 (SE;Q ID N0:12), ora fragment thereof sufficient to provide a binding site for an anti-PR01477 antibody. Preferably, the PR01477 fragment retains a qualitative biological activity of a native PR01477 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01477 polypeptide having the sequence of amino acid residues from about l to about 699, inclusive of Figure 10 (SEQ ID N0:12), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising IO the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01477 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01477 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI477 polypeptide by contacting the native PR01477 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1477 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
6. PR 1478 A cDNA clone (DNA56531-1648) has been identified that encodes a novel polypeptide having sequence identity with galactosyltransferase and designated in the present application as "PR01478."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID N0:17); or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01478 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 77 and about 1057, inclusive, of Figure 11 (SEQ ID N0:16). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human prouein cDNA in ATCC
Deposit No. 203286 WO 00/1Z~08 PCT/US99/20111 (DNA56531-1648), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poiypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203286 (DNA56531-1648).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID
N0:17), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and pra3uced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PFtOI478 polypeptide having the sequence of amino acid residues from about I to about 327, inclusive of Figure 12 (SEQ ID
N0:17}, or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specif c aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01478 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain (type Ii) has been tentatively identified as extending from about amino acid position ;L9 through about amino acid position 49 in the PRO1478 amino acid sequence .(Figure 12, SEQ ID N0:17). 'Therefore, a peptide including amino acids 50-327, with or without aunino acids I-28, is specificaaly embodied herein, as well as the nucleic acid encoding such a pegtide.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a} DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, .more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 327, inclusive of Figure 12 (SEQ ID
N0:17), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR014713 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments a:re from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about ~t0 nucleotides in length.
In another embodiment, the invention provides isolated PR01478 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01478 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 327 of Figure 12 (SEQ ID N0:17).
In another aspect, the invention concerns an isolated PR01478 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably apt least about 95% sequence identity to the wo oonZ7a8 PcrnJS99no111 sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID
N0:17).
In a further aspect, the invention concerns an isolated PFC01478 potypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 327 of Figure 12 (SEQ ID N0:17).
In yet another aspect, the invention concerns an isolated fRO 1478 polypeptide, comprising the sequence of amino acid residues 1 to about 327, inclusive of Figure 12 (SEQ ID NO:17), or a fragment thereof sufficient to provide a binding site for an anti-PR01478 antibody. Preferably, the PR01478 fragment retains a qualitative biological activity of a native PR01478 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a} a DNA molecule encoding a PR01478 polypeptide having the sequence of amino acid residues from about 1 to about 327, inclusive of Figure 12 (SEQ ID N0:17), or (b} the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01478 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01478 antibody.
In a further embodiment, the invention concerns. a method of identifying agonists or antagonists of a native PR01478 polypeptide, by contacting the native PR01478 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1478 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
7. PR0831 A cDNA clone (DNA56862-1343) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR083I".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0831 poiypeptide having the sequence of amino acid residues from about 1 or about l6 to about 73, inclusive of Figure 14 (SEQ ID
N0:22), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0831 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 40 or about 85 and about 258, inclusive, of Figure 13 (SEQ ID N0:21). Preferably, hybridization occurs under WO 00!12708 PCT/US99/20111 stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No: 203174 (DNA56862-1343) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203174 (DNA56862-1343).
In still a further aspect, the invention concerns an isolatNd nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80%a sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID
N0:22), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 470 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0831 polypeptide having the sequence oif amino acid residues from 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID N0:22), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0831 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide bas been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 14 (SEQ
iD N0:22).
in another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at Least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 16 to about 73, inclusive of Figure I4 (SEQ ID N0:22), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0831 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 13 (SEQ ID N0:2I).
In another embodiment, the invention provides isolated P1~0831 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0831 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about i6 to about 73 of Figure 14 (SEQ ID N0:22).
In another aspect, the invention concerns an isolated PFt0831 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID N0:22).
In a fitrther aspect, the invention concerns an isolated PR0831 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 73; inclusive of Figure 14 (SEQ ID N0:22).
In yet another aspect, the invention concerns an isolated PR0831 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 73, inclusive of Figure 14 (SEQ
ID N0:22), or a fragment thereof sufficient to provide a binding site for an anti-pR0831 antibody. Preferably, the PR083I fragment retains a qualitative biological activity of a native PR0831 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0831 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 73, inclusive of Figure 14 (SEQ ID N0:22), or (b) the complement of the DNA molecule of (a), and if the teost DNA
molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence :identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable fir expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
8. PR 113 A cDNA clone (DNA57254-1477) has been identified that encodes a novel polypeptide having sequence identity with leucine rich repeat proteins and designated in the present application as "PROl l I3."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01113 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROI I I3 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure i6 (SEQ ID N0:24), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROI113 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 214 and about 2061, inclusive, of Figure IS (SEQ ID N0:23). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203289 (DNA57254-1477), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203289 (DNA57254-1477).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, rnost preferably at least about 95% sequence identity to the sequence of amino acid residues from about i to about 616, inclusive of Figure 16 (SEQ ID
N0:24), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P:ft01113 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID
N0:24), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at lease about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a} or {b), isolating the u~st DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01113 polypeptide in its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 13 through about amino acid position 40 in the PR01113 amino acid sequence (Figure i6, SEQ ID N0:24}. Thus, also presented herein is a peptide comprising amino acids 4i-616, and optionally 1-12 of SEQ ID N0:24, and the nucleic acids encoding the same.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring of least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives; most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 616, inclusive of Figure I6 (SEQ ID
N0:24), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01113 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 84 nucleotides in length, preferably from about 20 to about GO nucleotides in length, mare preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
in another embodiment, the invention provides isolated PR01113 polypeptide encoded by any of the isolated micleic acid sequences hereinabove defined.
In a specific aspect,, the invention provides isolated native sequence PRO 11 I 3 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues i through 616 of Figure 16 (SEQ ID N0:24).
In another aspect, the invention concerns an isolated PR01113 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95.% sequence identity to the sequence of amino acid residues 1 to about 616; inclusive of Figure 16 (SEQ ID
N0:24).
In a further aspect, the invention concerns an isolated PR.O 1113 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 616 of Figure 16 (SEQ ID N0:24).
In yet another aspect, the invention concerns an isolated P:RO 1113 polypeptide, comprising the sequence of amino acid residues 1 to about 616, inclusive of Figure 16 (SEQ ID N0:24), or a fragment thereof sufficient to provide a binding site for an anti-PROl 113 antibody. Preferably, the PR01113 fragment retains a qualitative biological activity of a native PROI113 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with {a) a DNA molecule encoding a 1'ROII13 polypeptide having the sequence of amino acid residues from about 1 to about 616, inclusive of Figure 16 (SEQ ID N0:24), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 35 identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01113 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01113 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01113 polypeptide, by contacting the native PR01113 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROl 113 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
A cDNA clone (DNA57841-1522) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01194."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01194 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity; more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01194 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 81, inclusive.
of Figure 18 (SEQ ID N0:29}, or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nut;Ieic acid molecule encoding a PR01194 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 72 and about 251, inclusive, of Figure i7 (SEQ ID N0:28). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80%a sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203458 (DNA57841-1522), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptiide encoded by the human protein cDNA in ATCC
Deposit No. 203458 (DNA57841-1522).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identiity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID
N0:29), or the complement of the DNA of (a).
35 In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID
N0:29), or {b) tlae complement of the DNA molecule of (a), and, if the DNA molecule has at lease; about an 80% sequence identity, preferably at least abaut an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 22 to about 81, inclusive of Figure 18 (SEQ ID
N0:29), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01194 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are frvm~ about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01194 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01194 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 through 81 of Figure 18 (SEQ ID N0:29).
In another aspect, the invention concerns an isolated PR01194 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 81, inclusive of Figure 18 (SEQ ID
N0:29).
In a further aspect, the invention concerns an isolated PR01194 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 through 81 of Figure 18 (SEQ ID N0:29).
In yet another aspect, the invention concerns an isolated PB:Ol 194 polypeptide, comprising the sequence of amino acid residues 22 to about 81, inclusive of Figure 18 (SEQ~ ID N0:29), or a fragment thereof sufficient to provide a binding site for an anti-PR01194 antibody. Preferably, the PROI
194 fragment retains a qualitative biological activity of a native PR01194 poiypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI194 polypeptide having the sequence of amino acid residues from about 22 to about 81, inclusive of Figure 18 (SEQ ID N0:29), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising ~ 5 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agottists and antagonists of a native PROl I94 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01194 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01194 polypeptide, by contacting the native PR01194 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01194 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
10. PRO1110 A cDNA clone (DNA5872?-1474) has been identified, having homology to nucleic acid encoding myeloid upregulated protein that encodes a novel polypeptide, designated in the present application as "PRO 1110".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01110 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molectae encoding a PROl l 10 polypeptide having the sequence of amino acid residues from about I to about 322, inclusive of Figure 20 (SEQ ID N0:31), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1110 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 131 and about 1096, inclusive, of Figure I9 (SEQ ID N0:30). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about $5 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypegtide encoded by the human protein cDNA in ATCC
Deposit No. 203171 (DNA58727-1474) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypep~tide encoded by the human protein cDNA in ATCC Deposit No. 203171 (DNA58727-1474).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figure 20 (SEQ ID N0:31), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolatedl nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule tinder stringent conditions with (a) a DNA
molecule encoding a PROl I 10 polypeptide having the sequence of amino acid residues from 1 to about 322, inclusive of Figure 20 (SEQ ID N0:31), or {b) the complement of the DNA
molecule of {a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl I10 polypeptide,with or without the initiating methionine and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 41 to about amino acid position 60, from about amino acid position 66 to about amino acid position 85, from about amino acid position 101 to about amino acid position 120, from about amino acid position 137 to about amino acid position 153, from about amino acid position 171 to about amino acid position 192, from about amino acid position 205 to about amino acid position 226, from about amino acid position 235 to about amino acid position 255, and from about amino acid position 294 to about amino acid position 3I2 in the PR01110 amino acid sequence (Figure 20, SEQ ID N0:31).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 322, inclusive of Figure 21) (SEQ
ID N0:31), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI I 10 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 19 (SEQ ID N0:30).
In another emlmdiment, the invention provides isolated PRO1110 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO11I0 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 322 of Figure 20 (SEQ
ID NO:31).
In another aspect; the invention concerns an isolated PR01110 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about $5% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 322, inclusive of Figmve 20 (SEQ ID
N0:31).
In a further aspect, the invention concerns an isolated PRO 1110 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at feast albout 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 322, inclusive of Figure 20 (SEQ ID N0:31).
In yet another aspect, the invention concerns an isolated PRO 11 FO
polypeptide, comprising the sequence of amino acid residues I to about 322, inclusive of Figure 20 (SEQ ID N0:31), or a fragment thereof sufficient to provide a binding site for an anti-PRO1110 antibody. Preferably,. the PR01110 fragment retains a qualitative biological activity of a native PRO11I0 polypeptide.
In a still further aspect, the invention provides a poly~ptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO
1110 polypeptide having the sequence of amino acid residues from about 1 to about 322, inclusive of Figure 20 (SEQ ID N0:31), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PROlIIO
polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1110 antibody.
In a further embodiment, the invention concerns a methof, of identifying agonists or antagonists of a native PRO1110 polypeptide by contacting the native PRO1110 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide:
In a still further embodiment, the inventionconcerns a composition comprising a PRO 1 I 10 poiypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
11. PROI378 A cDNA clone (DNAS8730-1607) has been identified that encodes a novel secreted poiypeptide designated in the present application as "PROI378".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01378 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01378 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 335, inclusive of Figure 22 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01378 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1365 and about 2369, inclusive, of Figure 21 (SEQ ID N0:32). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203221 (DNAS8730-1607), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203221 (DNA58730-/607).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from 1 or about I6 to about 335, inclusive of Figure 22 (SEQ
ID N0:33), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 20 nucleotides, preferably at least about 50 nucleotides, and more preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01378 polypeptide having the sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 %
sequence identity, more preferably at least about a 90% sequence identity, mast preferably at Ieast about a 95%
sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI378 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from amino acid position 1 through about amino acid position IS in the sequence of Figure 2,2 (SEQ ID
N0:33).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more wo oonz7os PcTms99r~o1 preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 335, inclusive of Figure 22 (SEQ
ID N0:33), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a FR01378 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1PR01378 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1378 golypeptide, which in one embodiment, includes an amino acid sequence comprising residues I6 to 335 of Figure 22 (SEQ ID N0:33).
In another aspect, the invention concerns an isolated PR01378 polypegtide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ
ID N0:33).
In a further aspect, the invention concerns an isolated 1?RU1378 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S %
positives, more preferably at least about 90 % positives, most preferably at feast about 95 % positives when compared with the amino acid sequence of residues 16 to 335 of Figure 22 (SEQ ID N0:33).
In yet another aspect, the invention concerns an isolated PR O 1378 poIypeptide, comprising the sequence of amino acid residues 16 to about 335, inclusive of Figure 22 (SEQ ID N0:33), or a fragment thereof sufficient to provide a binding site for an anti-PR01378 antibody. Preferably, the PR01378 fragment retains a qualitative biological activity of a native PR01378 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI378 polypeptide having the sequence of amino acid residues from about 16 to about 335, inclusive of Figure 22 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
12. PR01481 A cDNA clone (DNA58732-1650) has been identified that encodes a novel polypeptide designated in the present application as "PR01481."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01481 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferable at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01481 polypeptide having the sequence of amino acid residues from 1 or about 24 to about ?~34, inclusive of Figure 24 (SEQ ID N0:41), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01481 polypeptide comprising DNA hybridizing to the complement of th.e nucleic acid between about residues 88 and about 1321, inclusive, of Figure 23 (SEQ ID N0:40}. Prefe:rably, hybridization occurs under stringent hybridization and wash conditions.
In a futrther aspect, the invention concerns an isolated nuicleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85'~ sequence identity,-more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203290 (DNA58732-1650), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein eDNA in ATCC
Deposit No. 203290 (DNA58732-1650).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to 'the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID
N0:41), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure: 24 (SEQ
ID N0:41), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated irucleic acid molecule comprising DNA encoding a PR01481 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted, truncated or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 24 (SEQ ID N0:41). The transmembrane domain has been tentatively identified as extending from about amino acid position 235 through about amino acid position 262 in the PR0148I amino acid sequence (Figure 24, SEQ ID N0:41).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poiypeptide scoring at least about 80 % positives, prei:erabIy at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 24 to about 334, inclusive of Figure 24 (SEQ
ID N0:41), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 11481 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolatedl PR014$1 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01481 polypegtide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 334 of Figure 24 (SEQ ID
N0:41).
I~ In another aspect, the invention concerns an isolated PR01481 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ
ID N0:41).
In a further aspect, the invention concerns an isolated PR.01481 polypeptide, comprising an amino acid IS sequence scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 through 334 of Figure 24 (SEQ ID NO:41).
In yet another aspect, the invention concerns an isolated PIt01481 polypeptide, comprising the sequence of amino acid residues 24 to about 334, inclusive of Figure 24 (SEQ ID N0:41), or a fragment thereof sufficient 20 to provide a binding site for an anti-PR01481 antibody. Preferably, the PR01481 fragment retains a qualitative biological activity of a native PR01481 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01481 polypeptide having the sequence of amino acid residues from about 24 to about 334, inclusive of Figure 24 (SEQ ID N0:41), or (b) 25 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the .
polypeptide from the cell culture.
3d In yet another embodiment, the invention concerns ago:nists and antagonists of a native pR01481 polypeptide. In a particular embodiment, the agonist or antagonist is an anti_pR01481 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01481 polypeptide, by contacting the native PR01481 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
35 In a still further embodiment, the invention concerns a composition comprising a PR01481 pnlypeptide, or an agonist or antagonist as hereinabove defined; in combination with a pharmaceutically acceptable carrier.
WO 00/1270$ PCT/US99/20111 13. PROll89 A cDNA clone (DNA58828-1519) has been identified that encodes a novel polypeptidehaving homology to E25 which is designated in the present application as "PROlIEl9."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a f 801189 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, mast preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01189 polypeptide having the sequence of amino acid residues from about I to about 263, inclusive of Figure 26 (SEQ ID N0:43), or (b) the complement of the DNA molecule of (a). .
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01189 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 79 and about 867, inclusive, of Figure 25 (SEQ ID N0:42). Preferably, hybridization occurs vender stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 ~'o sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 %. sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203172 (DNA58828-I519); or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypegtide encoded by the human protein cDNA in ATCC
Deposit No. 203172 (DNA58828-1519).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID
N0:43), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR.01189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID
N0:43), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the te:>t DNA
molecule.
In a specific aspect; the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01189 polypeptide with its transmembrane domain deleted or inactivated, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 53 through about amino acid position 75 in the PR01189 amino acid sequence (Figure 26, SEQ ID N0:43).
WO 00/12?08 PCT/US99/20111 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 263, inclusive of Figure 26 (SEQ ID
N0:43), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1 I89 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated :PRO/ 189 polypeptide encoded by any of the IO isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01189 polypeptide, which in one embodiment, includes an amino acid sequence comprising residurs i to 263 of Figure 26 (SEQ ID N0:43).
In another aspect, the invention concerns an isolated PR01189 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID
N0:43).
In a further aspect, the invention concerns an isolated PR01189 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 263 of Figure 26 (SEQ ID N0:43).
In yet another aspect, the invention concerns an isolated PR.O 1189 polypeptide, comprising the sequence of amino acid residues 1 to about 263, inclusive of Figure 26 (SEQ ID N0:43), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1189 antibody. Preferably, the PRO
1189 fragment retains a qualitative biological activity of a native PR01189 polypeptide.
In a still further aspect, the invention provides a polypepvide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01189 polypeptide having the sequence of amino acid residues from about 1 to about 263, inclusive of Figure 26 (SEQ ID N0:43), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonasts and antagonists of a native PR01189 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01189 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI189 polypeptide, by contacting the native PR01189 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
64.
In a still further embodiment, the invention concerns a cornposition comprising a PRO 1189 polypeptide, or an agonist or antagonist as hereinabove defined; in combination with a pharmaceutically acceptable carrier.
i4. PR01415 A cDNA clone (DNA58852-1637) has been identified that encodes a novel polypeptide; designated in the present application as "PR01415".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 polypeptide.
In one aspect; the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01415 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID
N0:50), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01415 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 148 or about 223 and about 996, inclusive, of Figure 27 {SEQ ID N0:49).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprisixtg DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°ro sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203271 (DNA58852-1637) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203271 (DNA58852-1637).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID
NO:50), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01415 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or (b) the complement of the DNA molecule of (a), and, if.the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, mast preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01415 poly~peptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated v~~riants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 28 (SEQ
ID NO:50). The transrnembrane domain has been tentatively identified as extending from about amino acid position 94 to about amino acid position 118 in the PR01415 amino acid sequence (Figure 28, S:EQ ID NO:50).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 8S% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR014~ 15 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be- derived from the nucleotide sequence shown in Figure 27 (SEQ ID N0:49).
1S In another embodiment, the invention provides isolated PR01415 polygeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO141S
polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 283 of Figure 28 (SEQ ID NO:50).
In another aspect, the invention concerns an isolated PRO1415 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID NO:50).
In a further aspect, the invention concerns an isolated PR01415 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives vvhen compared with the amino acid sequence of residues 1 or about 26 to about 283, inclusive of Figure 28 (SE',Q ID
N0:50).
In yet another aspect, the invention concerns an isolated PRO 1415 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 283, inclusive of Figure 28 {SEQ
ID NO:50), or a fragment thereof sufficient to provide a binding site for an anti-PR01415 antibody.
Preferably, the PR01415 fragment retains a qualitative biological activity of a native PR01415 polypeptide.
In a still further aspect, the invention provides a polypepride produced by {i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA raolecule encoding a PR01415 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 283, inclusive of Figure 28 (SEQ ID
NO:50), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PROI415 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR014I5 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01415 polypeptide by contacting the native PR0141 ~~ polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO1415 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
15. PR01411 A cDNA clone (DNA59212-1627) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01411."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01411 polypeptide.
1n one aspect, the isolated nucleic acid comprises DNA lhaving at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01411 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 440, inclusive of Figure 30 (SEQ ID N0:52), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01411 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 247 and about 1503, inclusive, of Figure 29 (SEQ ID NO:51). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having 2S at least about 80% sequence identity, preferably at least about 85%~
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203245 (DNA59212-1627), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203245 (DNA592I2-1527).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID
N0:52), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ ID
N0:52), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least ;about 95%
positives when compared with the amino acid sequence of residues 22 to about 440, inclusive of Figmre 30 (SEQ
ID N0:52), or (b) the complement of the DNA of (a).
1~ Another embodiment is directed to fragments of a PR01411 palypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, wore preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1PR01411 poiypeptide encoded by any of the 15 isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01411 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 through 440 of Figure 30 (SEQ ID
NO:52).
In another aspect, the invention concerns an isolated PRO1411 poIypeptide, comprising an amino acid 20 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ
ID N0:52).
In a further aspect, the invention concerns an isolated PRO1411 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least aibout 85%
positives, mare preferably at least 25 about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 through 440 of Figure 30 (SEQ ID N0:52).
In yet another aspect, the invention concerns an isolated PRO1411 poIypeptide, comprising the sequence of amino acid residues 22 to about 440, inclusive of Figure 30 (SEQ ID N0:52), or a fragment thereof sufficient to provide a binding site for an anti-PRO 1411 antibody. Preferably, the PR01411 fragment retains a qualitative 30 biological activity of a native PR01411 polypeptide.
In a still further aspect, the invention provides a polypeptiide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01411 polypeptide having the sequence of amino acid residues from about 22 to about 440, inclusive of Figure 30 (SEQ iD N0:52), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 35 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01411 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01411 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01411 polypeptide, by contacting the native PR01411 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1411 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
Ib. PR01295 IO A cDNA clone (DNA59218-1559) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01295."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01295 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01295 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 280, inclusive of Figure 32 (SEQ ID N0:54), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01295 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 261 and about 1046, inclusive, of Figure 31 (SEQ ID N0:53). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuclleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203287 (DNA59218-1559), or (b) the complement of the DNA molecule of (,a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCG
Deposit No. 203287 (DNA59218-1559).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID
N0:54), or the complement of the DNA of (a).
In a farther aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA raolecule encoding a PR01295 polypeptide having the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID
N0:54), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 280, inclusive of Figuzy: 32 (SEQ
ID N0:54), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR012S>5 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01295 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01295 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 280 of Figure 32 (SEQ ID
N0:54).
In another aspect, the invention concerns an isolated PRO:1295 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably .at least about 95% sequence identity to the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ
ID N0:54).
In a further aspect, the invention concerns an isolated PR01295 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 through 280 of Figure 32 (SEQ ID N0:54}.
In yet another aspect, the invention concerns an isolated PRO 1295 polypeptide, comprising the sequence of amino acid residues 19 to about 280, inclusive of Figure 32 (SEQ ID N0:54), or a fragment thereof sufficient to provide a binding site for an anti-PR01295 antibody. Preferably, the PR01295 fragment retains a qualitative biological activity of a native PR01295 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01295 polypeptide having the sequence of amino acid residues from about 19 to about 280, inclusive of Figure 32 (SEQ ID N0:54), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01295 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01295 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI295 polypeptide, by contacting the native PR0129S polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still farther embodiment, the invention concerns a composition comprising a PRO 1295 poiypeptide, or an agonist or antagonist as hereunabove defined, in combination with a pharmaceutically acceptable carrier.
17. PR01359 A cDNA clone (DNA59219-1613) has been identified that: encodes a novel polypeptide having sequence identity with sialytransferases and designated in the present application as "PR01359" polypeptides.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01359 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01359 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 299, inclusive of Figure 34 (SEQ ID N0:56), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01359 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 277 and about 1080, inclusive, of Figure 33 (SEQ ID N0:55). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~~~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203220 (DNA59219-1613}, or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203220 (DNA59219-1613).
In a still further aspect, the invention concerns an isolatec! nucleic acid molecule comprising {a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to .about 299, inclusive of Figure 34 (SEQ ID
N0:56), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PF101359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive. of Figure 34 (SEQ
ID N0:56), or (b) the complement of the DNA molecule of (a); and, if the DNA molecule has at least about as 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01359 polypeptide in its soluble, i.e. iransmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain (type II) has been tentatively identified as extending from about amino acid position 9 through about amino acid position 31 in the PROI359 amino acid sequence (Figure 34, SEQ ID N0:56).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 32 to about 299, inclusive of Figure; 34 (SEQ
ID N0:56), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01359 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01359 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1359 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 through 299 of Figure 34 (SEQ ID
N0:56).
In another aspect, the invention concerns an isolated PR01359 palypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 2S sequence of amino acid residues 32 to about 299, inclusive of Figtue 34 (SEQ ID N0:56).
In a further aspect, the invention concerns an isolated PROI359 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 through 299 of Figure 34 (SEQ ID N0:56).
In yet another aspect, the invention concerns an isolated PRO1359 polypeptide, comprising the sequence of amino acid residues 32 to about 299, inclusive of Figure 34 (SEQ ID N0:56), or a fragment thereof sufficient to provide a binding site for an anti-PR01359 antibody. Preferably, the PRO
1359 fragment retains a qualitative biological activity of a native PROI359 polypeptide In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI359 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 34 (SEQ ID N0:56), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or {b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agottists and antagonists of a native PR01359 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01359 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01359 polypeptide, by contacting the native PR01359 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention.concerns a composition comprising a PRO 1359 polypeptide, or an agonist or antagonist as hereinabove defined, in combination. with a pharmaceutically acceptable carrier.
18. PR01190 A cDNA clone (DNA59586-1520) has been identified that encodes a novel polypeptide designated in the present application as "PR01I90", and which has homology na CDO protein.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01190 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 {SEQ ID N0:58), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01190 poiypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 340 and about 3684, inclusive, of Figure 3S (SEQ ID N0:58). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203288 (DNA59586-1520), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203288 (DNA59586-1520).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poIypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about I to about 1115, inclusive of Figure 36 (SEQ ID
N0:58), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a I'R01190 polypeptide having the sequence of amino acid residues from about 1 to about 1 I 15, inclusive of Figure 36 (SEQ
ID N0:58), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1190 polypeptide, with one or more of its txansmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified in the PR01190 amino acid sequence shown in Figure 36 (SEQ ID
N0:58) as extending from about amino acid position 16 to about amino acid position 30 and from about amino acid position 854 to about amino acid position 879.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more IS preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 11 I5, inclusive of Figure 36 (SEQ
ID N0:58), or (b) the complement of the DNA of (a}.
Another embodiment is directed to fragments of a PR01190 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about: 40 nucleotides in length.
. In another embodiment, the invention provides isolated 1'R01190 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native ;sequence PR01190 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to I i 15 of Figure 36 (SEQ ID N0:58).
In another aspect, the invention concerns an isolated PRO 1190 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at Ieast about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues i to about 1115, inclusive of Figure 36 (SEQ
ID N0:58}.
In a further aspect, the invention concerns an isolated PR01190 palypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 1115 of Figure 36 (SEQ ID NO:S8).
In yet another aspect, the invention concerns an isolated PRO 1190 polypeptide, comprising the sequence of amino acid residues 1 to about 1115, inclusive of Figure 36 (SEQ ID N0:58), or a fragment thereof sufficient to provide a binding site for an anti-PR01190 antibody. Preferably, the PRO
1190 fragment retains a qualitative biological activity of a native PR01190 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01190 polypeptide having the sequence of amino acid residues from about 1 to about 1115, inclusive of Figure 36 (SEQ ID N0:58), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identify, more preferably at least about a 90 % sequence S identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01190 polypeptide. in a particular embodiment, the agonist or antagonist is an anti-PR01190 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01190 polypeptide, by contacting the native PR01190 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROl 190 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
19. 801772 A cDNA clone (DNA59817-1703) has been identified, having homology to nucleic acid encoding peptidase enzymes, that encodes a novel polypeptide, designated in the present application as "PR01772".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01772 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID
2S N0:63), or (b) the complement of the DNA molecule of {a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01772 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 93 or about 201 and about 1553, inclusive, of Figure 37 (SEQ ID NO:~2).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203470 (DNA59817-1703) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203470 (DNA59817-1703).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at Least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID
N0:63), or (b} the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 415 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01772 polypeptide having the sequence of amino acid residues from 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID N0:63), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereabIy at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01772 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid IS position 1 to about amino acid position 36 in the sequence of Figure 38 (SEQ ID N0:63). The transmembrane domain has been tentatively identified as extending from about amino acid position 313 to about amino acid position 331 in the PR01772 amino acid sequence (Figure 38, SEQ ID N0:63).
in another aspect, the invention concerns an isolated iwcleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least albout 95%
positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID N0:63), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO I7 72 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and maybe derived from the nucleotide sequence shown in Figure 37 (SEQ ID N0:62).
In another embodiment, the invention provides isolated PROi772 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the .invention provides isolated native sequence PROI772 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 37 to about 487 of Figure 38 (SEQ ID N0:63).
In another aspect, the invention concerns an isolated PR01772 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID N0:63).
In a further aspect, the invention concerns an isolated PR01772 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at feast about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID N0:63).
In yet another aspect, the invention concerns an isolated PRO 1772 polypeptide, comprising the sequence of amino acid residues 1 or about 37 to about 487, inclusive of Figure 38 (SEQ
ID N0:63), or a fragment thereof sufficient to provide a binding site for an anti-PROI772 antibody.
Preferably, the PROI772 fragment retains a qualitative biological activity of a native PROi772 poly~peptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI772 polypeptide having the sequence of amino acid residues from about 1 or about 37 to about 487, inclusive of Figure 38 (SEQ ID
N0:63), or (b) the complement of the DNA molecule of (a); and i.f the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns ago~nists and antagonists of a native PR01772 polypeptide. In a particular embodiment, the agonist or antagoni st is an anti-PROI772 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01772 polypeptide by contacting the native PROI772 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01772 polypeptide, or an, agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
20. PROI248 A cDNA clone (DNA60278-1530) has been identified, having homology to nucleic acid encoding PUT-2, that encodes a novel polypeptide, designated in the present application as "PR01248".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01248 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecae encoding a PROI248 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID
NO:b8), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0124$
polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 182 and about 670, inclusive, of Figure 39 (SEQ ID N0:67).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203170 (DNA60278-1530) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypepti~de encoded by the human protein eDNA in ATCC Deposit No. 203170 (DNA60278-1530).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID
N0:68), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolatexl nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01248 polypeptide having the sequence of amino acid residues from 1 or about 21 to about i83, inclusive of Figure 40 (SEQ ID N0:68), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01248 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure; 40 (SEQ
ID N0:68). The traasmembrane domain has been tentatively identified as extending from about amino acid position 90 to about amino acid position 1 I2 in the PR01248 amino acid sequence (Figure 40, SEQ ID N0:68).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID N0:68), or {b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01248 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, mare preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 39 (SEQ ID N0:67).
In another embodiment, the invention provides isolated PR01248 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PROI248 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 183 of Figure 40 (SEQ ID N0:68).
In another aspect, the invention concerns an isolated PRO:1248 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID N0:68).
In a further aspect, the invention concerns an isolated PRO 1248 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, mast preferably at least about 95 % positives when compared with the amino acid sequence of residues I or about 21 to about 183, inclusive of Figure 40 (SEQ ID N0:68}.
In yet another aspect, the invention concerns an isolated PR01248 polypeptide, comprising the sequence of amino acid residues I or about 21 to about 183, inclusive of Figure 40 (SEQ
ID N0:68), or a fragment thereof sufficient to provide a binding site for an anti-PR01248 antibody.
Preferably, the PR01248 fragment retains a qualitative biological activity of a native PR01248 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01248 polypeptide having\the sequence of amino acid residues from about 1 or about 21 to about 183, inclusive of Figure 40 (SEQ ID
N0:68), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (h), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable four expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonusts and antagonists of a native PR01248 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01248 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01248 polypeptide by contacting the native PR01248 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide:
In a still further embodiment, the invention concerns a composition comprising a PR01248 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
2I. PROi316 A cDNA clone (DNA60608-1577) has been identified, hawing homology to Dickkopf that encodes a novel polypeptide, designated in the present application as "PR01316."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01316 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01316 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01316 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 281 and about 987, inclusive, of Figure 41 (SEQ ID N0:69). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuc;ieic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%m sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human ptratein cDNA in ATCC Deposit No. 203126 I0 (DNA60608-1577), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203126 (DNA60608-1577):
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about' 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 26 to about 259, inclusive of Figure 42 (SEQ ID
N0:70), or the complement of the DNA of (a).
In a further aspect, the invention concern an isolated nucleic acid molecule having at least I5 nucleotides which hybridizes under stringent conditions with (a) a DNA molecule having a identity with a region spanning either .from residues 1-454 or from residues 1095-3130 of the Figure; 41 (SEQ
ID N0:69), or (b) the complement of the DNA molecule of (a). Alternatively, an isolated nucleic acid molecule having at least 15 nucleotides having at least about 80% sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95%
sequence identity to: (a) a DNA
molecule having a identity with a region spanning either from residues 1-454 or from residues 1095-3130 of the Figure 41 (SEQ ID N0:69), or (b) the complement of the DNA molecule of (a).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a. PROI316 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 25 in the sequence of Figure 42 (SEQ ID N0:70).
An N-glycosylation site has been identified at position 52 and a fungal Zn(2)-Cys{6) binuclear cluster has been identified at position 99.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 26 to about 259, inclusive of Figure 42 (SEQ
ID N0:70}, or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01316 polypeptide encoded by any of the WO 00/12708 PCTlUS99/20111 isolated nucleic acid sequences herein above defined.
In a specific aspect, the invention provides isolated native sequence PRO 1316 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 to 259 of Figure 42 (SEQ ID N0:70).
In another aspect, the invention concerns an isolated PRG1316 polypeptide, comprising an amino acid sequence having at least about $0% sequence identity, preferably at /cast about $5% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ
ID N0:70).
In a further aspect, the invention concerns an isolated PRO 1316 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 26 to 259 of Figure 42 (SEQ ID N0:70).
In yet another aspect, the invention concerns an isolated PRO 1316 polypeptide, comprising the sequence of amino acid residues 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or a fragment thereof sufficient to provide a binding site for an anti-PR01316 antibody. Preferably, the PRO
1316 fragment retains a qualitative biological activity of a native PR01316 polypepcide.
In a still further aspect, the invention provides a poIypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01316 polypeptide having the sequence of amino acid residues from about 26 to about 259, inclusive of Figure 42 (SEQ ID N0:70), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more.
preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture:
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR013I6 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01316 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01316 polypeptide, by contacting the native PR01316 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01316 polypeptide, or an agonist or antagonist as herein above defined, in combination with a pharmaceutically acceptable carrier.
22. PR01197 A cDNA clone (DNA60611-1524) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01197."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01197 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most WO OOJ12708 PCTIUS99J201 i 1 preferably at feast about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1197 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 363, inclusive of Figure 44 (SEQ ID N0:72), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01197 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 383 and about 1399, inclusive, of Figure 43 (SEQ ID N0:71). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203175 (DNA60611-1524), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203175 (DNA60611-1524).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID
N0:72), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 4.4 (SEQ
ID N0:72), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least aibout an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, mast preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 25 to about 363, inclusive of Figure 44 (SEQ
ID N0:72), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1197 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR.01197 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1197 polypeptide, which in one WO OO/I2?08 PCTlUS99/20111 embodiment, includes an amino acid sequence comprising residues 25 through 363 of Figure 44 (SEQ ID
N0:72}.
In another aspect, the invention concerns an isolated PR01197 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 363, inclusive of Figure 44 (SEQ
ID N0:72).
In a further aspect, the invention concerns an isolated PROl 197 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 through 363 of Figure 44 (SEQ iD .N0:72).
In yet another aspect, the invention concerns an isolated PRO 1197 poiypeptide, comprising the sequence of amino acid residues 25 to about 363, inclusive of Figure 44. (SEQ ID
N0:72), or a fragment thereof sufficient to provide a binding site for an anti-PR01197 antibody. Preferably, the PROI
197 fragment retains a qualitative biological activity of a native PR01197 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by {i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01197 polypeptide having the sequence of amino acid residues from about 25 to about 363, inclusive of Figure 44 (SEQ ID N0:72), or (b) the complement of the DNA molecule of (a), and if the test DNA nnolecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more: preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypepdde from the cell culture:
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01197 polypeptide. In a particular embodiment, the agonist or antagonist: is an anti-PR01197 antibody.
23. PR01293 A cDNA clone (DNA60618-1557) has been identified, having homology to nucleic acid encoding an immunoglobulin heavy chain variable region protein that encodes a :novel polypeptide, designated in the present application as "PR01293".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01293 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity;
preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01293 poIypeptide having the sequence of amino acid residues from about 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID
N0:77), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01293 polypeptide comprising DNA hybridizing to the complement of the: nucleic acid between about nucleotides 37 or about 94 and about 1059, inclusive, of Figure 45 (SEQ ID NO: i'6).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the htitttan protein cDNA in ATCC Deposit No. 203292 (DNA60618-1557) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203292 (DNA60618-1557).
In still a further aspect, the invention concerns an isolated. nucleic acid molecule comprising (a) DNA
encoding a pvlypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID
N0:77), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule Lender stringent conditions with (a) a DNA
molecule encoding a PR01293 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID N0:77), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01293 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 46 (SEQ
ID N0:77). The transmembrane domain has been tentatively identified as extending from about amino acid position 237 to about amino acid position 262 in the PR01293 amino acid sequence (Figure 46, SEQ ID N0:77).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID N0:77), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01293 poIypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 45 (SEQ ID N0:76).
In another embodiment, the invention provides isolated PR01293 polypeptide encoded by any of the isolated nucleic acid sequences hereinahove identified.
In a specific aspect, the invention provides isolated native sequence PR01293 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 341 of Figure 46 (SEQ ID N0:7?).
In another aspect, the invention concerns an isolated PR01293 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity; preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID N0:77).
In a further aspect, the invention concerns an isolated PR01293 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID N0:77}.
In yet another aspect, the invention concerns an isolated PF;01293 polypeptide, comprising the sequence of amino acid residues 1. or about 20 to about 341, inclusive of Figure 46 (SEQ ID N0:77), or a fragment thereof sufficient to provide a binding site for an anti-PR01293 antibody.
Preferably, the PR01293 fragment retains a qualitative biological activity of a native PR01293 polyF~eptide.
In a still further aspect, the invention provides a polypeptide produced by {i} hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01293 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 341, inclusive of Figure 46 (SEQ ID
N0:77), or (b) the complement of the DNA molecule of (a), and i:f the test DNA
molecule has at least about an 80 % sequence identity, preferably at lease about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01293 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01293 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI293 poiypeptide by contacting the native PR01293 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
in a still further embodiment, the invention concerns a com~,position comprising a PR01293 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
24. FR01380 A cDNA clone (DNA60740-1615) has been identified that: encodes a novel mufti-span transmembrane polypeptide designated in the present application as "PR01380".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01380 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molExule encoding a PR01380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID N0:79), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a .PROI380 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 36 and about 1460, inclusive, of Figure 47 (SEQ ID N0:78). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203456 (DNA60740-1615), or (b) the complement of the DNA molecule of (a): In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203456 (DNA60740-16IS).
In a still further aspect, the invention concerns an isolated nucleic acid molecule cotriprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about I to about 470, inclusive of Figure 48 (SEQ ID
N0:79), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P1Z01380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID
N0:79), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least. about an 80% sequence identity, preferably at least about an 8S % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01380 polypeptide, and its soluble variants (i.e. one or more transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule.
Transmembrane domains have been tentatively identified at about the following amino acid positions: 50-74, 105-127, 13S-153, 163-183, 228-252, 30S-330, and 448=472 in the PR01380 amino acid sequence (Figure 48, SEQ ID
N0:79).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poIypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 1 to about 470, inclusive of Figure 48 (SEQ ID
N0:79), or {b) the complement of the DNA of (a).
wo oonz7os PCT/US99/20111 Another embodiment is directed to fragments of a PR01380 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01380 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence.PR01380 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 470 of Figure 48 (SEQ ID N0:79).
In another aspect, the invention concerns an isolated PRO1380 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ ID
N0:79).
In a further aspect, the invention concerns an isolated PRO1380 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives ~yhen compared with the amino acid sequence of residues 1 to 470 of Figure 48 (SEQ ID N0:79).
In yet another aspect, the invention concerns an isolated PRO 1380 polypeptide, comprising the sequence of amino acid residues 1 to about 470, inclusive of Figure 48 (SEQ! ID N0:79), or a fragment thereof sufficient to provide a binding site for an anti-PR01380 antibody. Preferably, the PR01380 fragment retains a qualitative biological activity of a native PR01380 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01380 polypeptide having the sequence of amino acid residues from about 1 to about 470, inclusive of Figure 48 (SEQ ID N0:79), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypegtide, and (iii) recovering the polypeptide from the cell culture.
25. RP 01265"
A cDNA clone (DNA60764-1533) has been identified that encodes a novel polypeptide having homology to the Figl polypeptide and designated in the present application as "PR01265."
In one embodiment, the invention provides an isolated nuclleic acid molecule comprising DNA encoding a PR01265 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of amino acid residues from 1 or about about 22 to about 567, inclusive of Figure 50 (SEQ ID
N0:84), or (b) the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01265 polypeptide comprising DNA hybridizing to the complement of tt~e nucleic acid between aboutresidues 142 and about 1779, inclusive, of Figure 49 (SEQ ID N0:83). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203452 (DNA60764-1533); or (b) the complement of the -DNA molecule of (a). In a preferred embodiment, tire nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203452 (DNA60764-1533).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID
N0:84), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01265 polypeptide having the sequence of amino acid residues from about 22 to about 567, inclusive of Figure; 50 (SEQ
ID N0:84), or (b} the complement of the DNA molecule of (a), and; if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01265 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amizto acid position 1 through about amino acid position 21 in the sequence of Figure 50 (SEQ
1D N0:84).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poIypeptide scoring at least about 80% positives, pre~ferabiy at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 22 to about 567, inclusive of Figure 50 (SEQ
ID N0:84), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1265 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
8$
In another embodiment, the invention provides isolated PR01265 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01265 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 22 to 567 of Figure 50 (SEQ ID
N0:84)..
In another aspect, the invention concerns an isolated PRO 1265 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence~identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 567, inclusive of Fi,~gure SO (SEQ
ID N0:84).
In a further aspect, the invention concerns an isolated PROD 1265 polypeptide, comprising an amino acid IO - sequence scoring at least about 80% positives, preferably at least,about 85% positives, more preferably at least about 90% positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 22 to 567 of Figure 50 (SEQ ID N0:84).
In yet another aspect, the invention concerns an isolated PRO 1265 polypeptide, comprising the sequence of amino acid residues 22 to about 567, inclusive of Figure 50 (SEQ ID N0:84), or a fragment thereof sufficient 15 to provide a binding site for an anti-PR01265 antibody. Preferably, the PR01265 fragment retains a qualitative biological activity of a native PR01265 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI265 poIypeptide having the sequence of amino acid residues from about 22 to about 567, inclusive of Figure 50 (SEQ ID N0:84), or (b) 20 the complement of the DNA molecule of (a), and if the test DNA :molecule has at least about an 80% sequence identity, preferably at least about an $5 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
26. PR01250 A eDNA clone (DNA60775-1532) has been identified, having homology to nucleic acid encoding long chain fatty acid CoA ligase that encodes a novel polypeptide, designated in the present application as "PR01250".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI250 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence idenrity, preferably at least about 85% sequence identity, more preferably .at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01250 polypeptide having the sequence of amino acid residues from about 1 to about 739, inclusive of Figure 52 (SEQ ID N0:86), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR012S0 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 and about 2290, inclusive, of Figure Si (SEQ ID N0:85). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identify, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203173 (DNA60775-1532) or (b) the complement of the nucleic acid molecule of (a}. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203173 (DNA60775-1532).
In still a further aspect, the invention concerns an isolated. nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at lease about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID N0:86), or (b) the complement of the DNA of (a):
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01250 polypeptide having the sequence of amino acid residues from 1 to about 739, inclusive of Figure 52 (SEQ ID N0:86), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identify, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b}, isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01250 poIypeptide, with or without the initiating methionine, and its soluble, i.e., traasmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The type II
transmembrane domain has been tentatively identified as extending :from about amino acid position 61 to about amino acid position 80 in the PR01250 amino acid sequence (Figmve 52, SEQ ID
N0:86).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, prefi;rably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues I to about 739, inclusive of Figure 52 (SEQ ID
N0:86), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI250 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40~
nucleotides in length and may be derived from the nucleotide sequence shown in Figure S 1 (SEQ ID N0:85).
In another embodiment, the invention provides isolated PR01250 potypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01250 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues I to about 739 of Figure 52 (SEQ
ID N0:86).
In another aspect, the invention concerns an isolated PR() 1250 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, . most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 739, inclusive of Figure 52 (SEQ ID
N0:86).
In a fiu~ther aspect, the invention concerns an isolated PRt) 1250 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least .about 85 %
positives, more preferably at least . about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I to about 739, inclusive of Figure S2 (SEQ ID N0:86).
In yet another aspect, the invention concerns an isolated PR01250 polypeptide, comprising the sequence of amino acid residues l to about 739, inclusive of Figure 52 {SEQ ID N0:86), or a fragment thereof sufficient to provide a binding site for an and-PRO 1250 antibody. Preferabl3r, the PR01250 fragment retains a qualitative biological activity of a native PR01250 polypeptide.
In a still further aspect, the invention provides a poIypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01250 polypeptide having the sequence of amino acid residues from about 1 to about 739, inclusiive of Figure 52 (SEQ ID N0:86), or (b) the complement of the DNA molecule of (a), and if the test DNA miolecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at feast about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01250 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01250 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01250 polypeptide by contacting the native PROI250 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01250 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable corner.
27. PR 1475 A cDNA clone (DNA61185-1646) has been identified, having homology to nucleic acid encoding an N-acetylglucosaminyltransferase that encodes a novel polypeptide, designated in the present application as "PR01475".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01475 poIypeptide.
WO 00/I2?08 PCT/US99120111 In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01475 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 130 and about 2109, inclusive, of Figure 53 (SEQ ID N0:87). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203464 (DNA61185-1646) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203464 (DNA61 I85-1646).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88), or (b) the complement of the DNA of (a}.
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 180 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01475 polypeptide having the sequence of amino acid residues from 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least abut an 80 % sequence identity, prefereably ac Ieast about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably .at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01475 poIypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 38 to about amino acid position 55 in the PR01475 amino acid sequence (Figure 54, SEQ ID N0:88).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure'.>4 (SEQ
ID N0:88}, or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1475 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 53 (SEQ ID N0:87).
In another embodiment, the invention provides isolated PR01475 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated natiwe sequence PR01475 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 660 of Figure 54 (SEQ
ID N0:88).
In another aspect, the invention concerns an isolated PRO1475 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID
N0:88).
In a further aspect, the invention concerns an isolated PRCI1475 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88).
In yet another aspect, the invention concerns an isolated PRO 1475 polypeptide, comprising the sequence of amino acid residues 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88), or a fragment thereof sufficient to provide a binding site for an anti-PR01475 antibody. Preferably, the PR01475 fragment retains a qualitative biological activity of a native PR01475 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01475 polypeptide having the sequence of amino acid residues from about 1 to about 660, inclusive of Figure 54 (SEQ ID N0:88), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01475 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01475 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO147S polypeptide by contacting the native PR0147S polypeptide with a candidate molecule aad monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a cam9~osition comprising a PR01475 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
28. PR01377 A cDNA clone (DNA61608-1606) has been identified that encodes a novel mufti-span transmembrane polypeptide designated in the present application as "PR01377."
1n one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01377 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1377 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 307, inclusive of Figure 56 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01377 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 203 and about 1069, inclusive, of Figure 55 (SEQ ID N0:94). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~'o sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203239 (DNA61608-1606), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203239 (DNA61608-1606).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID
N0:95), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1377 polypeptide having. the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID
N0:95), or (b) the complement of the DNA molecule of {a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the nest DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01377 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and one or more of its transmembrane domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 5C (SEQ ID
N0:95). Transmembrane domain has been tentatively identified as eztending from about amino acid positions 37-56, 106-122, 21I-20, 240-260, and 288-304 in the PR01377 amino acid sequence (Figure 56, SEQ ID N0:95).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues I9 to about 307, inclusive of Figure 56 (SEQ
ID N0:95), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI3'77 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are fronn about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01377 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01377 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues I9 to 30? of Figure 56 (SEQ ID N0:95).
In another aspect, the invention concerns an isolated PR01377 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ
ID N0:95).
In a further aspect, the invention concerns an isolated PR01377 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 307 of Figure 56 (SEQ ID N0:95).
In yet another aspect, the invention concerns an isolated PRO 1377 polypeptide, comprising the sequence of amino acid residues 19 to about 307, inclusive of Figure 56 (SEQ ID N0:95), or a fragment thereof sufficient to provide a binding site for an anti-PR01377 antibody. Preferably, the PR01377 fragment retains a qualitative biological activity of a native PR01377 polypeptide.
In a still furtlxer aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI377 polypeptide having the sequence of amino acid residues from about 19 to about 307, inclusive of Figure 56 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, morn, preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
29. PR01326 A cDNA clone (DNA62808-1582) has been identified shat encodes a novel secreted polypeptide WO 00/12708 PCT/fJS99/Z0111 designated in the present application as "PR01326."
In one embodiment, the invention provides an isolated nucJieic acid molecule comprising DNA encoding a PR01326 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR013~6 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 401, inclusive of Figure 58 (SEQ ID NO:100), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated mucleic acid molecule encoding a PRO1326 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 199 and about 1314, inclusive, of Figure 57 (SEQ ID N0:99). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203358 (DNA62808-1582), or (b) the complement of the DNA molecule of"(a). In a preferred embodiutent, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203358 (DNA62808-1582).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identiity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID
NO: i00), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PItOI326 polypeptide having the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID
NO:100), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01326 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 58 (SEQ
ID NO:100).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poIypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 401, inclusive of Figure 58 (SEQ
ID NO:100), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01:326 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, .more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01326 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01326 polypeptide, which in one IO embodiment, includes an amino acid sequence comprising residues 30 to 401 of Figure 58 (SEQ ID NO:100).
In another aspect, the invention concerns an isolated PR01326 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to the sequence of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ
ID NO: i00).
In a further aspect, the invention concerns an isolated PR01326 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 30 to 401 of Figure 58 (SEQ ID NO:100).
In yet another aspect, the invention concerns an isolated PRO 1326 polypepdde, comprising the sequence of amino acid residues 30 to about 401, inclusive of Figure 58 (SEQ ID
NO:100), or a fragment thereof sufficient to provide a binding site for an anti-PRO1326 antibody. Preferably, the PR01326 fragment retains a qualitative biological activity of a native PR01326 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01326 polypeptide having the sequence of amino acid residues from about 30 to about 401, inclusive of Figure 58 (SEQ ID NO:100), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (~~a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
30. PR01249 A cDNA clone (DNA62809-1531) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01249".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA h<~ving at least about 80% sequence identity, WO 00112?08 PCT/US99I201I I
preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID
N0:102), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01249 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 3 or about 51 and about 3269, inclusive, of Figure 59 (SEQ ID NO:101). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity; most preferably at least about 9S% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203237 (DNA62809-1531) or (b) the complement of the nucleic acid mol~ule of (a}. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203237 (DNA62809-1531).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID
N0:102), or (b) the complement of the DNA of {a).
2n In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01249 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID N0:102), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01249 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., iransmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 16 in the sequence of Figure fi0 (SEQ
ID N0:102). The transmembrane domains have been tentatively identified as extending from about amino acid position 317 to about amino acid position 341, from about amino acid position 451 to about amino acid position 470, from about amino acid position 481 to about amino acid position 500, from about amino acid position 510 to about amino acid position 527, from about amino acid position 538 to about amino acid position 555, from about amino acid position 831 to about amino acid position 850, from about amino acid position 1016 to about amino acid position 1034 and from about amino acid position 1052 to about amino acid position 1070 in the PR01249 amino acid sequence (Figure 60, SEQ ID N0:102).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID N0:102), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01249 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about ~40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 59 (SEQ ID NO:101).
In another embodiment, the invention provides isolated F'ROI249 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01249 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 17 to about 1089 of Figure IS 60 (SEQ ID N0:102):
in another aspect, the invention concerns an isolated PR01249 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably ;at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ 1D NO:102).
In a further aspect, the invention concerns an isolated PR01249 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 8S %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives wlhen compared with the amino acid sequence of residues 1 or about I7 to about 1089, inclusive of Figure 60 (SEQ ID
NO:I02).
In yet another aspect, the invention concerns an isolated PRO1249 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID N0:102), or a fragraent thereof sufficient to provide a binding site for an anti-PR01249 antiibody.
Preferably, the PR01249 fragment retains a qualitative biological activity of a native PR01249 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01249 polypeptide having the sequence of amino acid residues from about 1 or about 17 to about 1089, inclusive of Figure 60 (SEQ ID
NO: I02), or (b) the complement of the DNA molecule of (a), and i:f the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule. under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
31. PR01315 A cDNA clone (DNA62815-1576) has been identified, having homology to nucleic acid encoding cytokine receptor family-4 proteins that encodes a novel polypeptide, designated in the present application as "PROI3I5".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01315 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity;
preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1315 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID
NO:104), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01315 polypeptide comprising DNA hybridizing to the complement of the; nucleic acid between about nucleotides 121 or about 205 and about 1446, inclusive, of Figure 61 (SEQ ID N0:103).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%. sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203247 (DNA62815-1576) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203247 (DNA62815-1576).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues i or about 29 to albout 442, inclusive of Figure 62 {SEQ ID
N0:104), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 500 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PROI315 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 442, inclusive of Figure 62 {SEQ ID N0:104), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR013I5 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., trartsmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figwre 62 (SEQ
ID N0:104). The transmembrane domain has been tentatively identified as extending from about amino acid position 140 to about amino acid position 163 in the PR01315 amino acid sequence (Figure 62, SEQ ID N0:104).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at Least about 80 % positives, preferably at least about SS % positives, more S preferably at least about 90 % positives, most preferably at least about 9S
% positives when compared with the amino acid sequence of residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID N0:104), or (b}
the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI31S polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are frorn about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 61 (SEQ ID N0:103).
In another embodiment, the invention provides isolated PR0131S polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
1S In a specific aspect, the invention provides isolated native sequence PR0131S polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 442 of Figure 62 (SEQ ID N0:104).
In another aspect, the invention concerns an isolated PROlL3IS polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably ,at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID N0:104).
In a further aspect, the invention concerns an isolated PRO 1315 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 1 or about 29 to about 442, inclusive of Figure 62 (SE~> ID
N0:104). , In yet another aspect, the invention concerns an isolated PRO I3I S
polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 442, inclusive of Figure 62 (SEQ
ID N0:104), or a fragment thereof sufficient to provide a binding site for an anti-PRO1315 antibody.
Preferably, the PROI3I5 fragment retains a qualitative biological activity of a native PR013IS polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0131S
polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 442, inclusive of Figure 62 (SEQ ID
N0:104}, or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 8S % sequence.
identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agot~ists and antagonists of a native PR01315 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01315 antibody.
In a further embodiment, the invention concerns a method of identifying agortists or antagonists of a native PROI3I5 polypeptide by contacting the native PR01315 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
S In a still further embodiment, the invention concerns a composition comprising a PRO 1315 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
32. PR01599 A cDNA clone (DNA62845-1684)has been identified that encodes a novel polypeptide having homology to Granzyme M and designated in the present application as "PR01599."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01599 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity;
preferably at least about 85 % sequence identity, more preferably at Ieast about 90 % sequence identity, most 1S preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01599 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 283, inclusive of Figure 64 (SEQ ID NO:111), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01599 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 and about 917, inclusive, of Figure 63 (SEQ ID NO:110}. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203361 (DNA62845-1684), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203361 (DNA62845-1684).
in a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poiypeptide having at least about &0% sequence idemity, preferably at least a6bui 8S% sequence identity, more preferably at least about 90% sequence identity, mast preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 (SEQ ID
NO:111), or the complement of the DNA of (a}.
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule emder stringent conditions with (a} a DNA molecule encoding a PR01599 polypeptide having the sequence of amino acid residues from about 3i to about 283, inclusive of lFigure 64 (SEQ
ID NO:111), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01599 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 64 (SEQ
ID NO:111).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives; more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 31 to about 283, inclusive of Figure 64 (SEQ
ID NO:111), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01599 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are fronn about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, miore preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01599 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect; the invention provides isolated native sequence PRO 1599 palypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 283 of Figure 64 (SEQ ID NO:111).
In another aspect, the invention concerns an isolated PR01599 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ
ID NO:111).
In a further aspect, the invention concerns an isolated PR01599 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 283 of Figure 64 (SEQ ID NO:111).
In yet another aspect, the invention concerns an isolated PRn 1599 polypeptide, comprising the sequence of amino acid residues 31 to about 283, inclusive of Figure 64 (SEQ ID
NO:111); or a fragment thereof sufficient to provide a binding site for an anti-PR01599 antibody. Preferably, the PR01599 fragment retains a qualitative biological activity of a native PR01599 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01599 polypeptide having the sequence of amino acid residues from about 31 to about 283, inclusive of Figure 64 {SEQ ID NO:111), or (b) the complement of. the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more; preferably at least about a 90% sequence WO 00/12708 PCT/US99/20i 1 t identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and {iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns a~;onists and antagonists of a native PR01599 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1S99 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1S99 polypeptide, by contacting the native PR0159~9 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01599 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
33. PR01430 A cDNA clone (DNA64842-1632) has been identified that: encodes a novel polypeptide having homology to reductase proteins, designated in the present application as "PR01430."
In one embodiment, the invention provides,an isolated nucleic acid molecule comprising DNA encoding a PR01430 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferabl;r at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01430 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 3:31, inclusive of Figure 66 (SEQ ID N0:116);
or (b) the complement of the DNA molecule of {a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01430 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 33 and about 1074, inclusive, of Figure 65 (SEQ ID NO:115). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DIVA having at least about 80 % sequence identity, preferably at least about 85 31;
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 rb sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203278 (DNA64842-1632), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203278 (DNA64842-1632).
In a still farther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID
N0:116), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about SO
WO 00/12708 PCT/US99l201I 1 nucleotides, and preferably at least about 100 and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01430 polypeptide having the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID N0:116), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 9'0 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DhfA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01430 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. 'Fhe signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 66 (SEQ ID
N0:116).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 18 to about 331, inclusive of Figure 66 (SEQ
ID N0:116), or (b} the complement of the DNA of {a}.
Another embodiment is directed.to fragments of a PR01430 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
in another embodiment, the invention provides isolated PR01430 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1430 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 331 of Figure 66 (SEQ ID N0:116).
In another aspect, the invention concerns an isolated PRO 1430 poIypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 331, inclusive of Figure 66 (SEQ
ID N0:116).
In a further aspect, the invention concerns an isolated PR01430 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I8 to 331 of Figure 66 (SEQ ID N0:116).
In yet another aspect, the invention concerns an isolated PR01430 polypeptide, comprising the sequence .
of amino acid residues 18 to about 331, inclusive of Figure 66 (SEQ ID
N0:116), or a fragment thereof sufficient to provide a binding site for an anti-PR01430 antibody. Preferably, the PR01430 fragment retains a qualitative biological activity of a native PROI430 poIypeptide.
In a still further aspect, the invention provides a poiypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule ent:oding a PR01430 polypeptide having the sequence of amino acid residues from about 18 to about 331, inclusive of Figure 66 (SEQ ID N0:116), or (b) the complement of the DNA molecule of (a}, and if the test DNA molecule has at least about an 80% sequence identity, preferably at feast about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01430 polypeptide. In a particular embodiment, the aganist or antagonist is an anti-PR01430 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01430 polypeptide, by contacting the native PR0143(1 polypeptide with a candidate molecule and monitoring a biological activity mediated by said palypeptide.
In a still further embodiment, the invention concerns a connposition comprising a PR01430 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
34. PROi374 A cDNA clone (DNA64849-1604) has been identified that encodes a novel poIypeptide having sequence identity with P4HA and designated in the present application as "PR01374."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01374 polypeptide.
in one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least abort 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01374 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 544, inclusive of Figure 68 (SEQ ID N0:118), or (b) the complement of the DNA molecule of (a).
in another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01374 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 78 and about I652, inclusive, of Figure 67 (SEQ ID N0:117). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203468 (DNA64849-1604), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein eDNA in ATCC
Deposit No. 203468 (DNA64849-1604).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID
N0:118), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a 1'R01374 polypeptide having the sequence of amino acid residues from about 20 to about 544, inclusive of Figure 68 (SEQ ID
N0:118), or (b) the complement of the DNA molecule of (a), and, if the DNA moleculle has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, mast preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 20 to about 544, inclusive of Figure 68 (SEQ
ID N0:118), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI374 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01374 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01374 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 544 of Figure 68 (SEQ ID
N0:118).
In another aspect, the invention concerns an isolated PR01374 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at feast about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ
ID N0:118).
In a further aspect, the invention concerns an isolated PRC11374 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives vvhen compared with the amino acid sequence of residues 20 through 544 of Figure 68 (SEQ ID N0:118).
In yet another aspect, the invention concerns an isolated PR01374 polypeptide, comprising the sequence of amino acid residues 20 to about 544, inclusive of Figure 68 (SEQ ID
N0:118), or a fragment thereof sufficient to provide a binding site for an anti-PR01374 antibody. Preferably, the PR01374 fragment retains a qualitative biological activity of a native PR01374 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01374 polypeptide having the sequence of amino acid residues from about 20 io about 544, inclusive of Figure 68 (SEQ ID N0:118), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 8S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA ,molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01374 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01374 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01374 polypeptide, by contacting the native PR01374 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the inventionconcerns a composition comprising a PRO 1374 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
35. PR01311 A cDNA clone (DNA64863-1573) has been identified that encodes a novel tetraspan polypeptide designated in the present application as "PR01311".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI311 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01311 polypegtide having the sequence of amino acid residues from 1 or about 4S to about 29.4, inclusive of Figure 70 (SEQ ID NO: I23), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01311 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 327 and about 1076, inclusive, of Figure 69 (SEQ ID N0:122). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85%> sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203251 (DNA64863-I573), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203251 (DNA64863-1573).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to the sequence of amino acid residues from about 4S to about 294, inclusive of Figure 70 (SEQ ID
NO:I23), or the complement of the DNA of {a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with {a) a DNA molecule encoding a PR01311 polypeptide having the sequence of amino acid residues from about 45 to about 294, inclusive of Figure 70 (SEQ ID
N0:123), or (b) the complement of the DNA molecule of (a), and, if the DIVA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01311 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble,, i.e. transmembrane domains deleted or inactivated wariants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 44 in the sequence of Figure 70 (SEQ ID
NO:I23). Four transmembrane domains has been tentatively identified as extending from about amino acid 22-42, 57-85, 94-116, and 230-257 in the PR01311 amino acid sequence (Figure 70, SEQ ID N0:123).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at /east about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 45 to about 294, inclusive of Figure 70 (SEQ
ID N0:123), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01311 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01311 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native; sequence PR01311 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 45 to 294 of Figure 70 (SEQ ID N0:123).
In another aspect, the invention concerns an isolated PRO1311 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at /east about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferabI;y at least about 95% sequence identity to the sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ
ID N0:123).
In a further aspect, the invention concerns an isolated PROI3I 1 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at /east about 85 %
positives, more preferably at least about ~ % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 45 to 294 of Figure 70 (SEQ ID N0:123).
In yet another aspect, the invention concerns an isolated PR01311 polypeptide, comprising the sequence of amino acid residues 45 to about 294, inclusive of Figure 70 (SEQ ID
N0:123), or a fragment thereof sufficient to provide a binding site for an anti-PR013I1 antibody. Preferably, the PR01311 fragment retains a qualitative biological activity of a native PR01311 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01311 polypeptide having the sequence of amino acid residues from about 4S to about 294, inci'.usive of Figure 70 (SEQ ID N0:123), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an $S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
36. PR01357 A cDNA clone (DNA64881-1602) has been identified, having homology to nucleic acid encoding the von Ebner minor salivary gland protein that encodes a novel polypeptide, designated in the present application as "PR013S7".
in one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR013S7 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoQing a PR013S7 poIypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID
N0:128), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated mtcleic acid molecule encoding a PR013S7 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 74 or about 137 and about 1525, inclusive, of Figure 71 (SEQ ID N0:127).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203240 (DNA64881-1602) or (b) the complement of the nucleic acid molecne of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203240 (DNA64881-1602).
In still a further aspect, the invention concerns an isolated rnucleic acid molecule comprising (a) DNA
encoding a polypeptide having at Least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID
N0:128), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 40 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01357 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID N0:128), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01357 polypeptide, with or withaut the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid po:>ition 21 in the sequence of Figure 72 (SEQ
iD N0:128).
In another aspect, the invention concerns an isolated rnxcleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, mare preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID N0:128), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01357 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about M~
nucleotides in length and may be derived from the nucleotide sequence shown in Figure 71 (SEQ ID N0:127).
In another embodiment, the invention provides isolated PR01357 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01357 polypeptide, which is certain embodiments, includes an amino acid sequence comprising residues 1 or about 22 to about 484 of Figure 72 (SEQ ID NO:128).
In another aspect, the invention concerns an isolated PR01:357 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure ?2 (SEQ ID N0:128).
In a further aspect, the invention concerns an isolated PR01357 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID
N0:128).
In yet another aspect, the invention concerns an isolated PRO 1357 polypeptide, comprising the sequence of amino acid residues 1 or about 22 to about 484, inclusive of Figure 72 (SEQ
ID N0:128), or a fragment thereof sufficient to provide a binding site for an anti-PR01357 antibody.
Preferably, the PR01357 fragment retains a qualitative biological activity of a native PR01357 polypeptide.
In a stilt further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01357 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 484, inclusive of Figure 72 (SEQ ID
N0:128), or (b) the complement of the DNA molecule of (a}, and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns ago~nists and antagonists of a native PR01357 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROi357 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01357 poiypeptide by contacting the native PR01357 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1357 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
37. PR01244 A cDNA clone (DNA64883-1526) has been identified that encodes a novel polypeptidehaving homology to Implantation-Associated Protein and designated in the present application as °PR01244."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01244 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01244 polypeptide having the sequence of amino acid residues from 1 or about 30 to about 335, inclusive of Figure 74 (SEQ ID N0:130), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01244 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 96 and about 1013, inclusive, of Figure 73 (SEQ ID N0:129). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203253 {DNA64883-1526), or (b) the complement of the DNA molecule of I;a). In a preferred embodiment, the nucleic 3S acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203253 (DNA64883-1526).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 335, inclusive of Figure 74 (SEQ ID
N0:130), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01244 polypeptide having the sequence of amino acid residues from about 30 to about 335, inclusive of Figure 74 (SEQ ID
N0:130), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity; more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a FROI244 polypeptide, with or without the N-terminal signal sequence andJor the initiating methionine, and its soluble, i.e. transmembrane domains deleted or-inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 74 (SEQ ID
N0:130). The transmembrane domains have been tentatively identified in the PRO 1244 amino acid sequence at about the following amino acid regions: 183-205, 217-137, 271-287, and 301-321.
In another aspect, the invention concerns an isolated .nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 335, inclusive of Figure 74 (SEQ
ID N0:130), or (b) the complement of the DNA of (a).
Another embodiment is directed tb fragments of a PR01244 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are front about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01244 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01244 polypeptide, which in one embodiment, includes an annino acid sequence comprising residues 30 to 335 of Figure 74 (SEQ ID N0:130).
In another aspect, the invention concerns an isolated PROI244 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at feast about 9S % sequence identity to the sequence of amino acid residues 30 to about 335, inclusive of Figure 74 (SEQ
ID N0:130).
In a further aspect, the invention concerns an isolated PR01.244 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence WO 00/12708 PCT/US99/2011 f of residues 30 to 335 of Figure 74 (SEQ ID N0:130).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01244 polypeptide having the sequence of amino acid residues from about 30 to about 335, inclusive of Figure 74 {SEQ ID NO: i30), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PRO1244 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01244 antibody.
In a further embodiment, the invention concerns a method of identifying agonises or antagonists of a native PR01244 polypeptide, by contacting the native PR0124~~ polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a connposition comprising a PRO 1244 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
38. PR01246 A cDNA clone (DNA64885-1529) has been identified, having homology to nucleic acid encoding bone-related sulphatase that encodes a novel polypeptide, designated in the present application as "PR01246".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01246 poIypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to (a) a DNA molecule encoding a PR01246 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID
N0:132), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1246 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides I 19 or about 164 and about 1726, inclusive, of Figure 75 (SEQ ID N0:131).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203457 (DNA64885-1529) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203457 (DNA64885-1529).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or about 16 t~o about 536, inclusive of Figure 76 (SEQ ID
NO:132), or (b) the complement of the DNA of {a}.
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01246 poiypeptide having the sequence of amino acid residues from 1 or about I6 to about 536, inclusive of Figure 76 {SEQ ID N0:132), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01246 poiypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identifed as extending from about amino acid position 1 to about amino acid position 16 in the sequence of Figure 76 (SEQ
ID N0:132).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID N0:132}, or (b) the complement of the DNA of {a).
Another embodiment is directed to fragments of a PRO I24G6 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are frotra about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 4G0 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 75 (SEQ ID N0:131}.
In another embodiment, the invention provides isolated PR01246 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01246 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 536 of Figure 76 (SEQ ID N0:132).
In another aspect, the invention concerns an isolated PROi246 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably a.t least about 95 % sequence identity to the 3s sequence of amino acid residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID N0:132).
In a further aspect, the invention concerns an isolated PROI246 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least 1 is about 90% positives, most preferably at Ieast about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID
N0:132).
In yet another aspect, the invention concerns an isolated PRO 1246 polypeptide, comprising the sequence of amino acid residues I or about 16 to about 536, inclusive of Figure 76 (SEQ
ID NO:I32), or a fragment thereof sufficient to provide a binding site for an anti-PR01246 antibody.
Preferably, the PR01246 fragment retains a qualitative biological activity of a native PR01246 polyp~eptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01246 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 536, inclusive of Figure 76 (SEQ ID
N0:132), or (b} the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at feast about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host ceil comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
in yet another embodiment, the invention concerns agonists and antagonists of a native PRO1246 polypeptide. In a particular embodiment, the agonist or antagonise is an anti-PR01246 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01246 polypeptide by contacting the native PR01246 1?olypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, tlxe invention concerns a composition comprising a PR01246 polypeptide, 24 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable earner.
39. PR01356 A cDNA clone (DNA64886-1601} has been identified, having homology to nucleic acid encoding clostridium perfringens enterotoxin receptor, that encodes a novel poIypepEide, designated in the present application as "PR01356".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01356 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% seqt<ence identity, more preferably at least about 9(?% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01356 polypegtide having the sequence of amino acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID
N0:134), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01356 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 194 and about 811, inclusive, of Figure 77 (SEQ ID N0:133).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most..preferably at least about 9:i % sequence identity to (a) a DNA molecule encoding the same mature polypeptide "encoded by the human protein cDNA in ATCC Deposit No. 20324I
(DNA64886-160I) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203241 (DNA64886-1601). w In still a further aspect, the invemion concerns an isolate d nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80%~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 ~or about 25 to about 230, inclusive of Figure 78 (SEQ ID
IO N0:134), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 20 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01356 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID N0:134), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI356 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide bas been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 78 (SEQ
ID N0:134). The transmembrane domains have been tentatively identified as extending from about ~unino acid position 82 to about amino acid position I02, from about amino acid position 117 to about amino acid position 140 and from about amino acid position 163 to about amino acid position 182 in the PR01356 :unino acid sequence (Figure 78, SEQ ID
N0:134).
In another aspect, the invention concerns an isolated nuacleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID N0:134), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI356 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 77 (SEQ ID N0:133).
In another embodiment, the invention provides isolated PRO1356 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01356 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 230 of Figure 78 (SEQ ID N0:134).
In another aspect, the invention concerns an isolated PR;01356 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferab.ty at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 230, inc.tusive of Figure 78 (SEQ ID N0:134).
In a further aspect, the invention concerns an isolated PRO 1356 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID
N0:134).
In yet another aspect, the invention concerns an isolated PR01356 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 230, inclusive of Figure 78 (SEQ
ID N0:134), or a fragment thereof su~cient to provide a binding site for an anti-PR01356 antibody.
Preferably, the PR01356 fragment i5 retains a qualitative biological activity of a native PR01356 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01356 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 230, inclusive of Figure 78 (SEQ ID
N0:134), or (b) the compleraent of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) ar (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01356 polypeptide. In a particular embodiment, the agonist or antagonise is an anti-PROI356 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01356 poIypeptide by contacting the native PROI356 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01356 poIypeptide, or an agonist or antagonist as hereinabove defined, in combination 'with a pharmaceutically acceptable carrier.
40. PR01275 A cDNA clone (DNA64888-1542) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01275."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01275 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, PCTlUS99/20t I 1 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1275 polypeptide having the sequence of amino acid residues from about 26 to about I 19, inclusive of Figure 80 (SEQ ID N0:136), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01275 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 112 and about 393, inclusive, of Figure 79 (SEQ ID N0:135). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203249 (DNA64888-1542), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203249 (DNA64888-1542).
In a still fizrther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, mare preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID
N0:136), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01275 polypeptide having the sequence of amino acid residues from about 26 to about 1I9, inclusive of Figure 80 (SEQ ID
N0:136), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity.to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns au isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at Least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 26 to about 119, inclusive of 1~igure 80 (SEQ
ID N0:136), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01275 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from aboue 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO1275 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01275 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 through 119 of Figure 80 (SEQ ID
N0:136).
In another aspect, the invention concerns an isolated PRO1275 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 26 to about 119, inclusive of Figure 80 (SEQ
ID N0:136).
In a further aspect, the invention concerns an isolated PR~01275 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about.95 % positives when compared with the amino acid sequence of residues 26 through 119 of Figure 80 (SEQ ID N0:136).
In yet another aspect, the invention concerns an isolated PF;01275 polypeptide, comprising the sequence of amino acid residues 26 to about 119, inclusive of Figure 80 (SEQ ID
NO:136), or a fragment thereof sufficient to provide a binding site for an anti-PR01275 antibody. Preferably, the PR01275 fragment retains a qualitative biological activity of a native PRO1275 polypepride.
I5 In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1275 polypeptide having the sequence of amino acid residues from about 26 to about 119, inclusive of Figure 80 (SEQ ID N0:136), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more: preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression o~f the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonusts and antagonists of a native PR01275 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01275 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01275 polypeptide, by contacting the native PR01275 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypepdde.
in a still further embodiment, the invention concerns a composition comprising a PR01275 poIypeptide, or an agonist or antagonist as hereinabove defined, in combination vvith a pharmaceutically acceptable corner.
41. 01274 A cDNA clone (DNA64889-1541) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01274."
In one embodiment, the invention provides an isolated nucleic: acid molecule comprising DNA encoding a PROI274 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01274 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 110, inclusive of Figure 82 (SEQ ID N0:138), , or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01274 poIypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 96 and about 353, inclusive, of Figure 81 (SEQ ID N0:137). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at ~ least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203250 (DNA64889-1541), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203250 (DNA64889-1541).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at Least about 90% sequence identity, roost preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about 110, inclusive of Figure 82 (SEQ ID
NO:I38), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about SO
nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01274 polypeptide having the sequence of amino acid residues from about 25 to about 110, inclusive of Figure 82 (SEQ ID
N0:138), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an $5% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 9S %
positives when compared with the amino acid sequence of residues 25 to about 110, inclusive of :Figure 82 (SEQ
iD N0:138), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI274 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO1274 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01274 polypeptide, which in one WO 00/1270$
embodiment, includes an amino acid sequence comprising residues 25 through 110 of Figure 82 (SEQ ID
N0:138).
In another aspect, the invention concerns an isolated pR.01274 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferablly at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 110, inclusive of Figure 82 (SEQ
ID NO: I38).
In a further aspect, the invention concerns an isolated PR01274 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably of Ieast about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 through I10 of Figure 82 (SEQ ID.N0:138).
0 In yet another aspect, the invention concerns an isolated PR01274 polypeptide, comprising the sequence of amino acid residues 25 to about 110, inclusive of Figure 82 (SEQ ID
N0:138}, or a fragment thereof sufficient to provide a binding site for an anti_pR01274 antibody. Preferably, the PROI274 fragment retains a qualitative biological activity of a native PR01274 polypeptide.
In a still further aspect, the invention provides a polypep~tide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI274 polypeptide having the sequence of amino acid residues from about 25 to about 110, inchtsive of Figure 82 (SEQ ID NO:138), or (b) the complement of the DNA rriolecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at Ieast about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01274 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01274 antibody.
In a further embodiment, the invention concerns a method of identifying agonists ox antagonists of a native PR01274 polypeptide, by contacting the native PR01274 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01274 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
42. PR014I2 A cDNA clone (DNA64897-1628) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01412."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01412 polypeptide.
3S In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01412 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 311, inclusive of Figure 84 (SEQ ID N0:140), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01412 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 226 and about 1074, inclusive, of Figure 83 (SEQ ID N0:139). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at leasE about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203216 (DNA64897-1628), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203216 (DNA64897-1628).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, mare preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 29 to about 311, inclusive of Figure 84 (SEQ ID
N0:140), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about i00 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PIItOI4i2 polypeptide having the sequence of amino acid residues from about 29 to about 3I1, inclusive of Figure 84 (SEQ ID
N0:140), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR41412 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 28 in the sequence of Figure 8.4 (SEQ ID
N0:140). The transmembrane domain has been tentatively identified as extending from about amino acid position 190 through about amino acid position 216 in the PR01412 amino acid sequence (Figure 84, SEQ ID N0:140).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 29 to about 311, inclusive of Figure 84 (SEQ
ID N0:140), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1412 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01412 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native: sequence PROI412 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 29 to 311 of Figure 84 (SEQ ID N0:140).
In another aspect, the invention concerns an isolated PROI412 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferabl'.y at least about 85% sequence identity, more preferably at least about 90% sequence identity, .most preferably at least about 95% sequence identity to the sequence of amino acid residues 29 to about 311, inclusive of Figure 84 (SEQ
ID N0:140).
In a further aspect, the invention concerns an isolated PROI412 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 29 to 311 of Figure 84 (SEQ ID N0:140).
In yet another aspect, the invention concerns an isolated PR01412 polypeptide, comprising the sequence of amino acid residues 29 to about 311, inclusive of Figure 84 (SEQ ID
N0:140), or a fragment thereof sufficient to provide a binding site for an anti-PR01412 antibody. Preferably, the PR01412 fragment retains a qualitative biological activity of a native PR01412 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR014I2 polypeptide having the sequence of amino acid residues from about 29 to about 311, inchtsive of Figure 84 (SEQ ID N0:140), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
43. PR01557 A cDNA clone (DNA64902-1667) has been identified that encodes a novel polypeptide having homology to chordin and designated in the present application as "PR01557".
In one embodiment, the invention provides an isolated nucIe:ic acid molecule comprising DNA encoding a PR01557 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PROI557 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 451" inclusive of Figure 86 (SEQ ID N0:142), or (b) the complement of the DNA molecule of (a).
WO 00/1270$ PCT/US99/20111 In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01557 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 362 and about 1639, inclusive, of Figure 85 (SEQ ID N0:141). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least abaut 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203317 (DNAb4902-1667), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203317 (DNA64902-1667).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID
N0:142), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a F'R01557 polypeptide having the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID
N0:142), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity. to (a) or (b), isolating the test DNA molecule.
In a specific.aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01557 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 25 in the sequence of Figure l36 (SEQ ID
N0:142).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
eroding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 26 to about 451, inclusive of Figure 86 (SEQ
ID N0:142), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO155 ii poIypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR.O1557 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01557 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 to 45I of Figure 86 (SEQ ID N0:142).
In another aspect, the invention concerns an isolated PR.OI557 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 26 to about 451, inclusive of Fiigure 86 (SEQ
ID N0:142).
In a further aspect, the invention concerns an isolated PR:O 1557 polypeptide, comprising an amino acid sequence scaring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 26 to 451 of Figure 86 (SEQ ID N0:142).
In yet another aspect, the invention concerns an isolated PR01557 polypeptide, comprising the sequence of amino acid residues 26 to about 451, inclusive of Figure 8~5 (SEQ ID
N0:142); or a fragment thereof sufficient to provide a binding site for an anti-PR01557 antibody. Preferably, the PROI557 fragment retains a qualitative biological activity of a native PR01557 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01557 polypeptide having the sequence of amino acid residues from about 26 to about 451, inclusive of Figure 86 (SEQ ID N0:142), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 2O the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonsts and antagonists of a native PROI557 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01557 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1557 polypeptide by contacting the native PR01557 ~polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01557 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
44. PR01285 A cDNA clone (DNA64903-1553) has been identified that encodes a novel secreted polypepti:de that is designated in the present application as "PR01286."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01286 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01286 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 93, inclusive of Figure 88 (SEQ ID N0:144), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01286 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 147 and about 37I, inclusive, of Figure 87 (SEQ ID N0:143). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at Least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the .same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203223 (DNA64903-1553), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203223 (DNA64903-1553).
In a stilt further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80%'o sequence ideneity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, nnost preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 tee about 93, inclusive of Figure 88 (SEQ ID
N0:144), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucieoddes, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0128b polypeptide having the sequence of amino acid residues from about 19 to about 93, inclusive of Figure E~8 (SEQ ID
N0:144), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the teat DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01286 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 88 (SEQ
ID N0:144}.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, prefi;rably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 93, inclusive of Figure 88 (SEQ ID
N0:144), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1286 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated! PROI286 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native; sequence PROI286 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 93 of Figure 88 (SEQ ID N0:144).
In another aspect, the invention concerns an isolated PR01286 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 93, inclusive of Figue 88 (SEQ ID
N0:144).
In a further aspect, the invention concerns.an isolated PR01286 poIypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at Least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 19 to 93 of Figure 88 (SEQ ID N0:144).
In yet another aspect, the invention concerns an isolated PROI286 palypeptide, comprising the sequence of amino acid residues 19 to about 93, inclusive of Figure 88 (SEQ ID N0:144), or a fragment thereof sufficient to provide a binding site for an anti-PR01286 antibody. preferably, the PR01286 fragment retains a qualitative biological activity of a native PR01286 polypeptide.
In a still further aspect, the invention provides a polypep~tide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01286 polypeptide having the sequence of amino acid residues from about 19 to about 93, inclusive of Figure 88 (SEQ ID N0:144); or (b) the complement of the DNA molecule of (a), and if the test DNA rnolecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more; preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA moiecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poIypeptide from the cell culture.
45. PROI294 A cDNA done (DNA64905-1558) has been identified, having homology to nucleic acid encoding olfactomedin, that encodes a novel polypeptide, designated in the present application as "PR01294".
In one embodiment, the invention provides an isolated nucleiic acid molecule comprising DNA encoding a PROI294 poIypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROI294 polypeptide having the sequence of amino acid residues from about I or about 22 to about 406, inclusive of Figure 90 (SEQ ID
N0:146), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nuclleic acid molecule encoding a PR01294 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 110 or about I73 and about 1327, inclusive, of Figure 89 (SEQ ID NC>:145).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In' a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 8-'i %
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9-'i % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203233 {DNA64905-1558) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polype~ptide encoded by the human protein cDNA in ATCC Deposit No. 203233 (DNA64905-1558).
In still a further aspect, the invention concerns an isolatf;d nucleic acid molecule comprising (a) DNA
I O encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 406, inclusive of Figure 90 (SEQ ID
N0:146), or (b) the complement of the DNA of (a).
In a further. aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01294 polypeptide having the sequence of amino acid residues from l or about 22 to about 406, inclusive of Figure 90 (SEQ ID N0:146), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity" prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01294 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 2i in the sequence of Figure 90 (SEQ
ID N0:146).
In another aspect, the invention concerns an isolated micleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least a>~out 95%
positives when compared with the amino acid sequence of residues 1 or about 22 to about 406, inclusive of Figure 90 (SEQ ID N0:146), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01294. polypeptide coding sequence that may f"md use as hybridization probes. Such nucleic acid fragments are from .about 20 to. about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 89 (SEQ ID N0:145).
In another embodiment, the invention provides isolated PR01294 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
wo aonz7os In a specific aspect, the invention provides isolated native sequence PR01294 polypeptide; which in certain embodiments, includes an amino acid sequence comprising residues I or about 22 to about 406 of Figure 90 (SEQ ID N0:146).
In another aspect, the invention concerns an isolated PROI294 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 22 to about 406, inc;lusive of Figure 90 (SEQ ID NO:146).
1n a further aspect, the invention concerns an isolated PP,01294 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 22 to about 406, inclusive of Figure 90 (SEQ ID
N0:146).
In yet another aspect, the invention concerns an isolated PRO 1294 polypeptide, comprising the sequence of amino acid residues 1 or about 22 to about 406, inclusive of Figure 90 (SEQ
ID N0:146), or a fragment thereof sufficient to provide a binding site for a~n anti-PROI294 antibody.
Preferably, the 1'R01294 fragment retains a qualitative biological activity of a native PR01294 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR01294 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 406, inclusive of Figure 90 (SEQ ID
N0:146), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment; the invention concerns agonists and antagonists of a native PRO1294 polypeptide. In a particular embodiment, the agonist or antagoni.5t is an anti-PR01294 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01294 polypeptide by contacting the native PR01294 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01294 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
3a 46. PR01347 A cDNA clone (DNA64950-1590) has been identified that encodes a novel polypeptide having sequence identity with butyrophilin and designated in the present application as "PR01347."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01347 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA haming at least about 80% sequence identity, preferably at least about $5 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PROI347 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 500, inclusive of Figure 92 (SEQ ID NO:148), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated. nucleic acid molecule encoding a PR01347 polypeptide comprising DNA hybridizing to the complement of tlhe-nucleic acid between about residues 234 and about 1682, inclusive, of Figure 91 (SEQ ID N0:147). Preferably, hybridization occurs under stringent hybridization and wash conditions.
in a farther aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at. least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203224 (DNA64950-1590), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203224 (DNA64950-1590).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 500, inclusive of Figure 92 (SEQ ID
N0:148), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at Ieast about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P:ROI347 poIypeptide having the sequence of amino acid residues , from about 18 to about 500, inclusive of Figure 92 (SEQ
ID N0:14$), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isollating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01347 polypeptide, with ar without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e, transmembrane domain deleted (or that terminus truncated) or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as-extending from amino acid position I through about amino acid position 17 in the sequence of Figure 92 (SEQ
ID N0:148). The transrnembrane domain has been tentatively identified as extending from about amino acid position 239 through about amino acid position 255 in the PR0134T amino acid sequence (Figure 92, SEQ ID
NO: I48).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 18 to about 500; inclusive of Figure 92 (SEQ
ID N0:148), or (b) the WO 00!12708 PCT/tTS99/20111 complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO:1347 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01347 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention grovides isolated native: sequence PR01347 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 through 500 of Figure 92 (SEQ ID
N0:148). _ IO In another aspect, the invention concerns an isolated PRiD1347 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 500, inclusive of Fil;ure 92 (SEQ
ID N0:148). _ In a further aspect, the invention concerns an isolated PR01347 poIypeptide, comprising an amino acid IS sequence scoring at least about 80% positives, preferably at least;bout 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 through 500 of Figure 92 (SEQ ID N0:148).
In yet another aspect, the invention concerns an isolated PIi;01347 polypeptide, comprising the sequence of amino acid residues 18 to about 500, inclusive of Figure 92 (SEQ ID
N0:148), or a fragment thereof 20 sufficient to provide a binding site for an anti-pR01347 antibody.
preferably, the PR01347 fragment retains a qualitative biological activity of a native PR01347 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01347 polypeptide having the sequence of amino acid residues from about 18 to about 500, inclusive of Figure 92 (SEQ ID N0:148), or (b) 25 the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more: preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
30 In yet another embodiment, the invention concerns agonists and antagonists of a native PR01347 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01347 antibody.
In a further embodiment, the invention concerns a methodL of identifying agonists or antagonists of a native PR01347 polypeptide, by contacting the native PR01347 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
35 In a still further embodiment, the invention concerns a composition comprising a PRO 1347 polypeptide, or an agonist or antagonist as hereinabove defined, in combination vvith a pharmaceutically acceptable carrier.
WO 0U~12708 4?. PR01305 A cDNA clone (DNA649S2-1568) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0130S".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0130S polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR0130S polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID
NO:1S3), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0130S
polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 126 or about 201 and about 899, inclusive, of Figure 93 (SEQ ID NO: llS2).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S °o sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S%~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203222 (DNA649S2-1568) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poiypeptide encoded by the human protein cDNA in ATCC Deposit No. 203222 (DNA649S2-1568).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID
NO:I53), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule order stringent conditions with (a) a DNA
molecule encoding a PR0130S polypeptide having the sequence of .amino acid residues from 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID NO:1S3), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 8S % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 9S% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI30S polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 94 (SEQ
ID NO:IS3).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at.least about 90% positives; most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 258; inclusive of Figure 94 (SEQ ID N0:153), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1305 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 93.(SEQ ID N0:152).
ld In another embodiment, the invention provides isolated PR01305 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specifc aspect, the invention provides isolated native sequence PROI305 polypeptide; which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 258 of Figure 94 (SEQ ID N0:153).
15 In another aspect, the invention concerns an isolated PRO1305 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID N0:153).
In a further aspect, the invention concerns an isolated PRCI1305 polypeptide, comprising an amino acid 20 sequence scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 258, inclusive of Figure 94 (SE;Q ID
N0:153).
In yet another aspect, the invention concerns an isolated PRO 1305 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 258, inclusive of Figure 94 (SEQ
ID N0:153), or a fragment 25 thereof sufficient to provide a binding site for an anti-PROi305 anitibody.
Preferably, the PR01305 fragment retains a qualitative biological activity of a native PR01305 palypeptide.
in a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with {a) a DNA molecule encoding a PR01305 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 258, inclusive of Figure 94 (SEQ ID
30 N0:153), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable ifor expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
48. PR01273 A cDNA clone (DNA65402-1540) has been identified that encodes a novel polypeptide having sequence identity with lipocalins and designated in the present application as "PR01273. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI273 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from 1 or about 21 to about lti3, inclusive of Figure 96 (SEQ ID N0:158), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01273 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 and about 514, inclusive, of Figure 9S (SEQ ID N0:157). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85°o sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203252 (DNA6S402-1540), or (b) the complement of the DNA molecule of (a). In a preferred embodithent, the nucleic acid comprises a DNA encoding the same mature polypeptide enc<xled by the human protein cDNA in ATCC
Deposit No. 203252 (DNA65402-1540).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identily, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues from about 21 to aibout 163, inclusive of Figure 96 (SEQ ID
NO:1S8), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about SO
nucleotides, and preferably at least about 100 nucleotides and prodluced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from about 21 to about 163, inclusive of Figure 96 (SEQ ID
NO:ISB), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 8S % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 21 to about 163, inclusive of Figure 96 (SEQ
ID NO:1S8), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1273 ;polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, WO 00/12708 Pfr'T/US99I20111 preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucteoades in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01273 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
in a specific aspect, the invention provides isolated native sequence PRO1273 polypeptide, which in one S embodiment, includes an amino acid sequence comprising residues Z1 through 163 of Figure 96 (SEQ ID
N0:158).
In another aspect, the invention concerns an isolated PRO1273 potypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at.least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferabl3r at least about 95% sequence identity to the sequence of amino acid residues 21 to about 163, inclusive of Fil;ure 96 (SEQ
ID N0:158).
In a further aspect, the invention concerns an isolated PRO12?3 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives ~,vhen compared with the amino acid sequence of residues 21 through 163 of Figure 96 (SEQ ID N0:158).
1 S In yet anothef aspect, the invention concerns an isolated PR01273 polypeptide, comprising the sequence of amino acid residues 21 to about 163, inclusive of Figure 96 (SEQ ID
N0:158), or a fragment thereof sufficient to provide a binding site for an anti-PR01273 antibody. Preferably, the PR01273 fragment retains a qualitative biological activity of a native PR01273 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01273 polypeptide having the sequence of amino acid residues from about 21 to about 163, inclusive of Figure 96 (SEQ ID N0:158), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising 2S the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01273 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01273 antibody.
In a further embodiment, the invention concerns a method: of identifying agonists or antagonists of a native PR01273 polypeptide, by contacting the native PROI273 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01273 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
3S 49. PR01302 A cDNA clone (DNA6S403-1565) has been identified that encodes a novel polypeptide having sequence identity with CD33 and designated in the present application as "PR.OI302. "
WO 00/I2708 PCT/US99/ZOll l In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01302 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA, having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01302 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 4.63, inclusive of Figure 98 (SEQ ID NO: I60}, or (b} the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated .nucleic acid molecule encoding a PR01302 polypeptide comprising DNA hybridizing to the complement of ttte nucleic acid between about residues 88 and about 1431, inclusive, of Figure 97 (SEQ ID N0:159). Prefc;rably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85'% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203230 (DNA65403-1565), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203230 (DNA65403-1565).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about $5 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to.the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID
NO:160), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PICOI302 polypeptide having the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID
N0:160), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01302 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted (or truncated form) or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position i5 in the asequence of Figure 98 (SEQ ID N0:160).
3S The transmembrane domain has been tentatively identified as extending from about amino acid position 351 through about amino acid position 370 in the PR01302 amino acid ;sequence (Figure 98, SEQ ID N0:160).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
WO 00/12708 PCT/tJS99/20111 encoding a poIypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives; most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 463, inclusive crf Figure 98 (SEQ
ID N0:160), or (b) the complement of the DNA of (a}.
Another embodiment is directed to fragments of a PR01302 polypeptide coding sequence that may find S use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01302 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native ;sequence PROI302 polypeptide, which in ane embodiment, includes an amino acid sequence comprising residues 16 through 463 of Figure 98 (SEQ ID
NO:160).' In another aspect, the invention concerns an isolated PRCI1302 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 16 to about 463, inclusive of Figure 98 (SEQ
ID N0:160).
In a further aspect, the invention concerns an isolated PR01302 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95,% positives when compared with the amino acid sequence of residues 16 through 463 of Figure 98 (SEQ ID NO:I60).
In yet another aspect, the invention concerns an isolated PRO 1302 polypeptide, comprising the sequence of amino acid residues 16 to about 463, inclusive of Figure 98 (SEQ ID
N0:160), or a fragment thereof sufficient to provide a binding site for an anti-PR01302 antibody. Preferably, the PR01302 fragment retains a qualitative biological activity of a native PROI302 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
raolecule under stringent conditions with (a) a DNA molecule encoding a PR01302 polypeptide having the sequence of amino acid residues from about 16 to about 463, inclusive of Figure 98 (SEQ ID N0:160), or (b}
the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at Least about an 85% sequence identity, more. preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poiypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01302 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01302 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1302 polypeptide, by contacting the native PRO1302 polypeptide with a candidate molecule and monitoring a biological activity mediated by said poIypeptide.
WO 00/12708 PCT/US99I2011 i In a still further embodiment, the invention concerns a composition comprising a PRO 1302 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
50. PR01283 A cDNA clone (DNA65404-1551} has been identified, having homology to nucleic acid encoding odorant binding protein,.that encodes a novel polypeptide, designated in the present application as "PROI283".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01283 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01283 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID
N0:162), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01283 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 45 or about 96 and about 554, inclusive, of Figure 99 (SEQ ID NO:1li1).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuc;Ieic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203244 (DNA65404-1551) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC Deposit No. 203244 (DNA65404-1551).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or about 18 to about 170, inclusive of Figure 100 (SEQ ID
NO:I62), or (b) the complement of the DNA of (a}.
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PROI283 polypeptide having the sequence of amino acid residues from I or about i8 to about 170, inclusive of Figure 100 (SEQ iD NO: i62), or (b) the counplement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, ;prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01283 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is WO 00/12?08 PCT/US991201 I 1 complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 100 (SEQ
ID N0:162).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 18 to about i70, inclusive of Figure 100 (SEQ ID N0:162), or (b) the complement of the DNA of (a}.
Another embodimetu is directed to fragments of a PR01283 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 99 (SEQ ID NO:I61).
In another embodiment; the invention provides isolated PR01283 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01283 polypeptide, which in certain embodiments, includes an amino acid sequence comprising :residues 1 or about 18 to about 170 of Figure 100 (SEQ ID N0:162) In another aspect, the invention concerns an isolated PR01283 palypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID N0:162).
In a further aspect, the invention concerns an isolated PR01283 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least albout 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives vrhen compared with the amino acid sequence of residues 1 or about 18 to about I70, inclusive of Figure 100 (SIEQ ID
N0:162).
In yet another aspect, the invention concerns an isolated PR~01283 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 170, inclusive of Figure 100 (SEQ ID N0:162), or a fragment thereof sufficient to provide a binding site for an anti-PROI283 antibody.
Preferably, the PR01283 fragment retains a qualitative biological activity of a native PR01283 polypeptide.
In a still further aspect, the invention provides a polypepdde produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule er,~coding a PR01283 polypeptide having the sequence of amino acid residues from about 1 or about 18 to atbut 170, inclusive of Figure 100 (SEQ iD
N0:162), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to {a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01283 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01283 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01283 polypeptide by contacting the native PR01283 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a com~oosition comprising a PRO 1283 golypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
SI. PR01279 A cDNA clone (DNA65405-1547) has been identified, having homology to nucleic acid encoding neuropsin that encodes a novel polypeptide, designated in the present application as "PR01279".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01279 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01279 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID
N0:170), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01279 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 106 or about 160 and about 855, inclusive, of Figure 101 (SEQ ID N0:1~69}.
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, mast preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203476 (DNA65405-1547) or (b) the complement of the nucleic acid moIec:ule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypepti.de encoded by the human protein cDNA in ATCC Deposit No. 203476 (DNA65405-1547).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at feast about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID
N0:170), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule mxder stringent conditions with (a) a DNA
molecule encoding a PR01279 poIypeptide having the sequence of amino acid residues from I or about 19 to about 250, inclusive of Figure 102 (SEQ ID N0:170), ar (b) the connplement of the DNA molecule of (a), and, WO 00/12708 PCT/US9912011 t if the DNA molecule has at least about an 80 % sequence identity" prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at feast about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01279 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is S complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 102 (SEQ
ID N0:170).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at feast about 95%
positives when compared with the amino acid sequence of residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID N0:170), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01279 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, IS preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about ~10 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 101 (SEQ ID N0:1.69).
In another eml~diment, the invention provides isolated P~R01279 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO1279 polygeptide, which in certain embodiments, includes an amino acid sequence comprising :residues 1 or about 19 to about 250 of Figure 102 (SEQ ID N0:170).
In another aspect, the invention concerns an isolated PR0.1279 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more 2S preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID N0:170).
In a further aspect, the invention concerns an isolated PRO 1279 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about90 % positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 1 or about 19 to about 250, inclusive of Figure 102 (S1:Q ID
N0:170).
In yet another aspect, the invention concerns an isolated PR01279 goIypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID N0:170), or a fragment thereof sufficient to provide a binding site for an anti-PR01279 antibody.
Preferably, the PR01279 fragment retains a qualitative biological.activity of a native PR01279 polype;ptide.
In a still further aspect, the invention provides a poIypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01279 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 250, inclusive of Figure 102 (SEQ ID
N0:170), or (b) the complement of the DNA molecule of (a), andl If the test DNA molecule'has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01279 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01279 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01279 polypeptide by contacting the native PR01279 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01279 polypeptide, or an agonist or antagonist as hereinabove defused, in combination with a pharmaceutically acceptable carrier.
52. PR01304 A cDNA clone (DNA65406-1567) has been identified, having homology to nucleic acid encoding FK506 binding protein that encodes a novel polypegtide, designated in the present application as "PR01304".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI304 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01304 polypeptide having the sequence of amino acid residues from about 1 to about 222, inclusive of Figure 104 (SEQ ID N0:180), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01304 poIypeptide comprising DNA hybridizing to the complement of the; nucleic acid between about nucleotides 23 and about 688, inclusive, of Figure 103 {SEQ ID N0:179). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuclleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203219 (DNA65406-1567} or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 2032I9 (DNA65406-1567).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 222, inclusive of Figure I04 (SEQ ID N0:180), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
rnolecuie encoding a PROI304 polypeptide having the sequence of amino acid residues from I to about 222, inclusive of Figure i04 (SEQ ID N0:180), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI304 polypeptide, with or without the initiating methionine, or is complementary to such encoding nucleic acid molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 222, inclusive of Figure 104 (SEQ
ID N0:180), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0130~4 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 84 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 103 (SEQ ID NO:1'79).
In another embodiment, the invention provides isolated PR01304 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01304 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues I to about 222 of Figure 104 (SEQ
ID N0:180).
In another aspect, the invention concerns an isolated PR01304 poiypeptide, comprising an amino acid sequence having at least about 80 %a sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 222, inclusive of Figurc; 104 (SEQ
ID N0:180).
In a further aspect, the invention concerns an isolated PR01304 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 222, inclusive of Figure 104 (SEQ ID N0:180).
In yet another aspect, the invention concerns an isolated PRO 1304 polypeptide, comprising the sequence of amino acid residues I to about 222, inclusive of Figure 104 (SEQ ID
N0:180), or a fragment thereof sufficient to provide a binding site for an anti-PR01304 antibody. Preferably, the PR01304 fragment retains a qualitative biological activity of a native PR01304 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with {a) a DNA molecule encoding a PR01304 polypeptide having the sequence of amino acid residues from about 1 to about 222, inclusive of Figure 204 (SEQ ID N0:180), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or {b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression ~of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agortists and antagonists of a native PR01304 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01304 antibody.
1n a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01304 polypeptide by contacting the native PR01304 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO i 304 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
53. PROI317 A cDNA clone (DNA65408-2578) has been identified that encodes a novel secreted polypeptide that shares homology with human CD97. The novel polypeptide is designated in the present application as "PROi317".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 74; .inclusive of Figure 106 (SEQ ID N0:189), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nwcleic acid molecule encoding a PR013I7 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 60 and about 227, inclusive, of Figure 105 (SEQ ID N0:188). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203217 (DNA65408-1578), or (b) the complement of the DNA molecule of (.a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203217 (DNA65408-1578).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more.preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 74, inclusive of Figure 106 {SEQ ID
N0:189), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P:R0131'7 polypeptide having the sequence of amino acid residues from about 19 to about 74, inclusive of :Figure 106 (SEQ
ID N0:189), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), iscdating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as I S extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 106 (SEQ
ID N0:189).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 74, inclusive of :Figure 106 (SEQ
ID N0:189), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0131.7 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are front about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated P~R01317 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR013I7 polypeptide, which in one embodiment, includes an amino acid sequence comprising residue:. 19 to 74 of Figure 106 (SEQ ID N0:189).
In another aspect, the invention concerns an isolated PR01317 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 74, inclusive of Figure 106 (SEQ
ID N0:189).
In a further aspect, the invention concerns an isolated PRO 1317 polypegtide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 8S %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 74 of Figure 106 (SEQ ID N0:189}.
WO 00112708 PC'TIUS991201I1 In yet another aspect, the invention concerns an isolated PRO 1317 polypeptide, comprising the sequence of amino acid residues 19 to about 74, inclusive of Figure 106 (SEQ ID
N0:189), or a fragment thereof sufficient to provide a binding site for an anti-PR013I7 antibody. Preferably, the PROI317 fragment retains a qualitative biological activity of a native PR01317 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1317 polypeptide having the sequence of amino acid residues from about I9 to about 74, inclusive of Figure 106 (SEQ iD N0:189), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypepiide, and (iii) recovering the polypeptide from the cell culture.
54. PR01303 A cDNA clone (DNA65409-1566) has been identified that encodes a novel polypeptide having sequence identity with proteases including neuropsin and designated in the present application as "PR01303."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01303 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01303 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 248, inclusive of Figure 108 (SEQ ID N0:194), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated mxcleic acid molecule encoding a PR01303 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 172 and about 864, inclusive, of Figure 107 (SEQ ID N0:193). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85%~ sequence identity, more preferably at least about 90% sequence identity, most preferably at leasf about 95%~ sequence identity to (a) a DNA molecule encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203232 (DNA65409-1566), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203232 (DNA65409-1566).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
3S encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 18 to aibout 248, inclusive of Figure 108 (SEQ ID
14'7 N0:194), or the complement of the DNA of (a}.
In a further aspect, the invention concerns an isolated nus:leic acid molecule having at (east about SO
nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01303 polypeptide having the sequence of amino acid residues from about 18 to about 248, inclusive of 1~igure 108 (SEQ
ID N0:194), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 8S % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S% sequence identity to (a) or (b); isol'~ating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90 % positives, most preferably at least about 9S %
positives when compared with the amino acid sequence of residues 18 to about 248, inclusive of Figure 108 (SEQ
ID N0:194), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1303 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from. about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01303 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01303 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 through 248 of Figure 108 (SEQ ID
N0:194).
In another aspect, the invention concerns an isolated PR01303 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 18 to about 248, inclusive of Figure 108 (SEQ
ID N0:194).
In a further aspect, the invention concerns an isolated PR01303 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 18 through 248 of Figure 108 (SEQ ID N0:194).
In yet another aspect, the invention concerns an isolated PR01303 polypeptide, comprising the sequence of amino acid residues 18 to about 248, inclusive of Figure 108 (SEQ ID
N0:194), or a fragment thereof sufficient to provide a binding site for an anti-PR01303 antibody. Preferably, the PR01303 fragment retains a qualitative biological activity of a native PR01303 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01303 polypeptide having the sequence of amino acid residues from about 18 to about 248, inclusive of Figure 108 (SEQ ID N0:194), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence WO 00/12708 PCT/US99l20111 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01303 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01303 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01303 polypeptide, by contacting the native PR01303 p~olypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01303 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
55. PR01306 A cDNA clone (DNA65410-1569) has been identifiedthaten;codes a novel polypeptide having homology to AIF1/daintain and designated in the present application as "PR01306".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01306 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA Naming at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID N0:196), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01306 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 106 and about 555, inclusive, of Figure 109 (SEQ ID N0:195). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203231 (DNA65410-1569), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203231 (DNA65410-1569).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID
N0:196), or the complement of the DNA of (a).
In aY-further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides'; and pr,~ferably ar least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of figure 110 (SEQ ID
NO:I96), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, prelferably at Least about 8S% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 150, inclusive of Figure 110 (SEQ
ID NO:I96), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01306 polypeptide coding sequence that may f nd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, mare preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about ~40 nucleotides in length.
In another embodiment, the invention provides isolated P1Et01306 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1306 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 150 of Figure 110 (SEQ ID N0:196).
In another aspect, the invention concerns an isolated PROI306 poiypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 150, inclusive of Figure 110 (SEQ
ID N0:196).
In a further aspect, the invention concerns an isolated PR01306 poiypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at Least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 150 of Figure 110 {SEQ ID N0:196).
In yet another aspect, the invention concerns an isolated PRt)1306 polypeptide, comprising the sequence of amino acid residues 1 to about 150, inclusive of Figure 110 {SEQ ID
N0:196), or a fragment thereof sufficient to provide a binding site for an anti-PR01306 antibody. Preferably, the PR01306 fragment retains a qualitative biological activity of a native PR01306 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with {a) a DNA molecule encoding a PR01306 polypeptide having the sequence of amino acid residues from about 1 to about 150, inclusive of Figure 110 (SEQ ID N0:196), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agottists and antagonists of a native PR01306 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROI306 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01306 polypeptide, by contacting the native PR01306 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01306 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
56. PR01336 A cDNA clone (DNA65423-1595) has been identified that encodes a novel polypeptide having sequence identity with slit and designated in the present application as "PRO1336."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01336 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01336 polypeptide having the sequence of amino acid residues from I or about 28 to about 1523, inclusive of Figure 112 (SEQ ID
NO:198), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01336 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 164 and about 4651, inclusive, of Figures 111A-B (SEQ ID NO:197). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%. sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No: 203227 (DNA65423-1595), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide enr~~ded by the human protein cDNA in ATCC
Deposit No. 203227 (DNA65423-1595).
In a still further aspect, the invention concerns an isolatedl nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure.112 (SEQ ID
N0:198), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule WO OOlIZ708 PCT/US99lZO1l l under stringent conditions with (a) a DNA molecule encoding a PR.01336 polypeptide having the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure 112 (SEQ
ID N0:198), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule :has at least about an $0% sequence identity, preferably at least about am 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least abt~ut 95%
positives when compared with the amino acid sequence of residues 28 to about 1523, inclusive of 1~igure 112 (SEQ ID N0:198), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01336 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about b0 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about AGO
nucleotides in length.
In another embodiment, the invention provides isolated PR01336 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01336 polypeptide, which in one embodiment, includes an amino acid sequence comprising residue s 28 through 1523 of Figure 112 (SEQ ID
N0:198).
In another aspect, the invention concerns an isolated PROI336 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably apt least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably an least about 95% sequence identity to the sequence of amino acid residues 28 to about 1523; inclusive of Figure 112 (SEQ
ID N0:198).
In a further aspect, the invention concerns an isolated PR01.336 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 28 through 1523 of Figure 112 (SEQ ID N0:198).
In yet another aspect, the invention concerns an isolated PRC>1336 polypeptide, comprising the sequence of amino acid residues 28 to about 1523, inclusive of Figure 112 (SEQ ID
N0:198), or a fragment thereof sufficient to provide a binding site for an anti-PR01336 antibody. Preferably, the PR01336 fragment retains a qualitative biological activity of a native PR01336 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01336 polypeptide having the sequence of amino acid residues from about 28 to about 1523, inclusive of Figure 112 (SEQ ID N0:198), or (b) the complement of the DNA molecule of (a), and if the test :DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01336 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0133fi antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01336 polypeptide, by contacting the native PR01336 ~polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1336 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
57. PR01278 A cDNA clone (DNA66304-1546) has been identified that encodes a novel polypeptidehaving homology to Iysozyme C and designated in the present application as "PR01:278."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01278 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01278 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 148, inclusive of Figure 114 (SEQ ID N0203), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated mucleic acid molecule encoding a PR01278 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 198 and about 584, inclusive, of Figure 113 (SEQ ID N0:202). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 %o sequence identity to (a) a DNA molecule enc~iing the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203321 (DNA66304-1546), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide enGxled by the human protein cDNA in ATCC
Deposit No. 203321 (DNA66304-1546).
In a still firrther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ ID
N0:203), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P1Et01278 polypeptide having the sequence of amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ
ID N0:203), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule lzas at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably <tt least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isol<~ting the test DNA molecule.
In a specific aspect, the invention, provides an isolated nucleic acid molecule comprising DNA encoding a PROI278 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position l through about amino acid position 19 in the sequence of Figure 114 (SEQ ID
N0:203).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at /east about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 148, inclusive of Figure 114 (SEQ
ID N0:203), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI278 poiypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in Length.
In another embodiment, the invention provides isolated PR01278 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01278 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 to 148 of Figure 114 (SEQ ID N0:203).
In another aspect, the invention concerns an isolated PROI278 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 148, inclusive of Figure 114 (SEQ
ID N0:203).
In a further aspect, the invention concerns an isolated PR011278 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at Least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 to 148 of Figure 114 (SEQ ID N0:203).
In yet another aspect, the invention concerns an isolated PR01278 polypeptide, comprising the sequence of amino acid residues 20 to about 148, inclusive of Figure l I4 {SEQ ID
N0:203), or a fragment thereof sufficient to provide a binding site for an anti-PR01278 antibody. Preferably, the PR01278 fragment retains a qualitative biological activity of a native PR01278 poLypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI278 poiypeptide having the sequence of amino acid residues from about 20 to about 148, inclusive of Figure 114 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host dell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii} recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agouists and antagonists of a native PR01278 poiypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01278 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01278 polypeptide, by contacting the native pR01278 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a stall further embodiment, the invention.concerns a composition comprising a PRO1278 polypeptide, IO or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
58. PR01298 A cDNA clone (DNA66511-1563) has been identified that encodes a novel polypeptide having sequence identity with glycosyltxansferases and designated in the present application as "PR01298. "
I s In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01298 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 8s% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01298 polypeptide having 20 the sequence of amino acid residues from 1 or about 16 to about 323, inclusive of Figure 116 {SEQ ID N0:210), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nu,cieic acid molecule encoding a PR01298 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 139 and about 1062, inclusive, of Figure 115 (SEQ ID N0:209). Preferably, hybridization occurs under stringent 25 hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid raoIecule comprising DNA having at least about 80% sequence identity, preferably at least about 8s% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9s % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203228 30 (DNA66s I1-1s63), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203228 (DNA66511-1s63):
In a still fut-ther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence 35 identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues from about 16 to.about 323, inclusive of Figure 116 (SEQ ID
N0:2I0), or the complement of the DNA of (a).
Iss In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P~R01298 polypeptide having the sequence of amino acid residues from about 16 to about 323, inclusive of Figure 116 (SEQ
ID N0:210), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b); isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least albout 95%
positives when compared with the amino acid sequence of residues 16 to about 323, inclusive of Figure 116 (SEQ
ID N0:210), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1298 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 I5 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01298 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1298 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 through 323 of Figure 116 (SEQ ID
N0:210).
In another aspect, the invention concerns an isolated PR01L298 poiypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably .at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably .at feast about 95 % sequence identity to the sequence of amino acid residues 16 to about 323, inclusive of Figure 116 (SEQ
ID N0:210).
In a further aspect, the invention concerns an isolated PRO,:l298 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least a);but 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 through 323 of Figure 116 (SEQ ID N0:2I0).
In yet another aspect, the invention concerns an isolated PR01298 polypeptide, comprising the sequence of amino acid residues 16 to about 323, inclusive of Figure 116 (SEQ ID
N0:210), or a fragment thereof sufficient to provide a binding site for an anti-PR01298 antibody. Preferably, the PR01298 fragment retains a qualitative biological activity of a native PR01298 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROI298 polypeptide having the sequence of amino acid residues from about 16 to about 323, inclusive of Figure 116 (SEQ ID N0:210), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01298 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01298 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI298 polypeptide, by contacting the native PROI298 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1298 polypeptide, or an agonist or antagonist as hereinabove defmed,.in combination with a pharmaceutically acceptable earner.
59. PR 1301 A cDNA clone (DNA66512-1564) has been identified that encodes a novel polypeptide having homology to cytochrome P450 and designated in the present application as ":PR01301."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0130I polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01301 poiypeptide having the sequence of amino acid residues from 1 or about 19 to about 462., inclusive of Figure 118 (SEQ ID N0:212), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01301 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 97 and about 1428, inclusive, of Figure lI7 (SEQ ID N0:21I). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuclleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203218 (DNA66512-1564), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203218 (DNA66512-1564).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, me~st preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 462, inclusive of Figure i I8 (SEQ ID
N0:212), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01301 polypeptide having the sequence of amino acid residues from about 19 to about 462, inclusive of Figure 118 (SEQ
ID N0:212), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at /east about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DIVA encoding a PR01301 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine and its soluble; i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 1118 (SEQ ID
N0:212). The transmembrane domain has been tentatively identified as extending from about amino acid position 271 through about amino acid position 290 in the PR01301 amino acid sequence (Figure 118, SEQ ID N0:212).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more is preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 462, inclusive of lFigure 118 (SEQ
ID N0:212), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0130t polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PF~01301 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1301 polypeptide, which in one 2s embodiment, includes an amino acid sequence comprising residues 119 to 462 of Figure 118 (SEQ ID N0:212).
In another aspect, the invention concerns an isolated PR01301 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 19 to about 462, inclusive of Figure 11$ (SEQ
ID N0:212).
la a further aspect, the invention concerns an isolated PRO 1301 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 462 of Figure 118 (SEQ ID N0:212).
In yet another aspect, the invention concerns an isolated PR01301 polypeptide, comprising the sequence 3s of amino acid residues 19 to about 462, inclusive of Figure 118 (SEQ ID
N0:212), or a fragment thereof sufficient to provide a binding site for an anti-PR01301 antibody. Preferably, the PR01301 fragment retains a qualitative biological activity of a native PROI301 polypeptide.
lsg WO OOII2708 PCTlUS99IZ0I I 1 in a still farther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01301 polypeptide having the sequence of amino acid residues from about 19 to about 462, inclusive of Figure 118 (SEQ ID N0:212), or (b) the complement of the DNA molecule of {a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to I;a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
60. PR01258 ~ A cDNA clone (DNA66519-1535) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01268."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01268 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA leaving at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity; most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01268 polypeptide having the sequence of amino acid residues from about 1 to about 140, inc;Iusive of Figure 120 (SEQ ID N0:214}, or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01268 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 89 and about 508, inclusive, of Figure 119 (SEQ ID N0:213}. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203236 (DNA66519-1535), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203236 (DNA66519-1535).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, mast preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID
N0:214), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about SO
nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1268 polypeptide having the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID
N0:214), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to {a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucJleic acid molecule comprising DNA encoding a PR01268 polypeptide, with one or more of its soluble, i.e. transmembrane, domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. Transmembrane domains has been tentatively identified at about amino acids 12-28 (type II), 51-66, and 107-I24 iin the PROI268 amino acid sequence (Figure 120, SEQ ID N0:214).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a} DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 140, inclusive of lFigure 120 (SEQ
ID N0:214), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1268 polypeptide coding sequence that may find IS use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about '20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01268 polypegtide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1268 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 140 of Figure 120 (SEQ ID N0:214}.
In another aspect, the invention concerns an isolated PR01.268 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 140, inclusive of Figure; 120 (SEQ
ID N0:214).
In a further aspect, the invention concerns an isolated PROI:268 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 140 of Figure 120 (SEQ ID N0:214).
In yet another aspect, the invention concerns an isolated PR01268 polypeptide, comprising the sequence of amino acid residues 1 to about 140, inclusive of Figure 120 {SEQ ID
N0:214), or a fragment thereof sufficient to provide a binding site for an anti-PR01268 antibody. Preferably, the PR01268 fragment retains a qualitative biological activity of a native PR01268 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by {i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01268 polypeptide having the sequence of amino acid residues from about 1 to about 140, inclusive of Figure 120 (SEQ ID N0:214), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence i60 identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
S 61. PR012ti9 A cDNA clone (DNA66520-1536) has been identified that encodes a novel polypeptide having homology to granulocyte peptide A and designated in the present application as "PR01269."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01269 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR() 1269 polypeptide having the sequence of amino acid residues from 1 or about 21 to about l9fi, inclusive of Figure 122 (SEQ ID N0:216), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01269 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 and about 613, inclusive, of Figure 121 (SEQ ID N0:215). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at Least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203226 (DNA66520-1536), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203226 (DNA66520-1536).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% seguence identity; preferably at least about 85% sequence identity, more preferably at least. about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ ID
N0:216), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01269 polypeptide having the sequence of amino acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ
iD N0:216), or (b) the complement of the DNA molecule of (a), and, if itte DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more. preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule. , In a specific aspect, the invention provides an isolated nuc:leic acid molecule comprising DNA encoding a PROI269 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position l through about amino acid position 20 in the sequence of Figure 122 (SEQ ID
N0:216).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 21 to about 196, inclusive of Figure 122 (SEQ
ID N0:21)6, or (b) the complement of the DNA of (a). .
Another embodiment is directed to fragments of a PR01269 polypeptide coding sequence that may fmd else as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides 'in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated F'R01269 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01269 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 196 of Figure 122 (SEQ ID N0:216).
In another aspect, the invention concerns an isolated PRO 1269 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 196, inclusive of Figure I22 (SEQ
ID N0:216).
In a further aspect, the invention concerns an isolated PRO1269 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 196 of Figure 122 (SEQ ID N0:216).
In yet another aspect, the invention concerns an isolated PRU1269 polypeptide, comprising the sequence of amino acid residues 21 to about 196, inclusive of Figure 122 (SEQ ID
N0:216), or a fragment thereof sufficient to provide a binding site for an anti-PROI269 antibody. Preferably, the PRO1269 fragment retains a qualitative biological activity of a native PR01269 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule en<;oding a PR01269 polypeptide having the sequence of a~mitto acid residues from about 21 to about 196, inclusive of Figure 122 (SEQ ID NO:216), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01269 poiypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01269 antibody.
In a further embodiutent, the invention concerns a method of identifying agonists or antagonists of a native PROi269 polypeptide, by contacting the native PR01269~ polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01269 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
62. PR01327 A cDNA clone (DNA66521-1583) has been identified, having homology to nucleic acid encoding neurexoplilin, that encodes a novel polypeptide, designated in the present application as "PR01327".
In one embodiment, the inventionprovides an isolated nucleic acid molecule comprising DNA encoding a PR01327 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01327 polypeptide having the sequence of amino acid residues from about 1 or about 15 to aiboui 252, inclusive of Figure 124 (SEQ ID
N0:218), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01327 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 55 or about 97 and about 810, inclusive, of Figure 123 (SEQ ID N0:2:17).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Ieast about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature. polypeptide encoded by the human protein cDNA in ATCC Deposit No. 243225 (DNA66521-1583) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203225 (DNA66521-1583).
In still a further aspect, the invention concerns as isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about IS to about 252, inclusive of Figure 124 (SEQ ID.
N0:218), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 260 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PROI327 polypeptide having the sequence of .amino acid residues from 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID N0:218}, or (b) the complement of the DNA molecule of (a), and, WO 00lI2708 PCT/US99/20111 if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01327 poIypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic. acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 14 in the sequence of Figure 124 (SEQ
ID N0:218).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, prE;ferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID N0:218), or (b}
the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI327 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, IS preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 123 (SEQ ID N0:217}.
In another embodiment, the invention provides isolated PR01327 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native; sequence PROI327 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about IS to about 2S2 of Figure 124 (SEQ ID N0:218).
In another aspect, the invention concerns an isolated PR01327 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID N0:2I8).
In a further aspect, the invention concerns an isolated PROI327 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID
N0:2I8).
In yet another aspect, the invention concerns an isolated PR01327 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 252, inclusive of Figure 124 (SEQ ID N0:218), or a fragment thereof sufficient to provide a binding site for an anti-PR01327 antibody.
Preferably, the PR01327 fragment retains a qualitative biological activity of a native PROI327 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01327 polypeptide having the sequence of amino acid residues from about i or about 15 to about 252, inclusive of Figure 124 (SEQ ID
I~
N0:218), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence. identity, most preferably at least about a 95 % sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for ezpression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01327 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01327 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01327 polypeptide by contacting the native PR01327 polypeptide with a candidate molecule and monitoring a biological activity mediated by said poIypeptide.
In a still further embodiment, the invention concerns a cotr~position comprising a PRO 1327 poiypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
63. PROI382 A cDNA clone {DNA66526-1616) has been identified that encodes a novel polypegtide having homology to cerebellin and designated in the present application as "PR01382."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01382 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PRO 1382 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 201, inclusive of Figure 126 (SEQ ID N0:220), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01382 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 418 and 2$ about 939, inclusive, of Figure 125 (SEQ ID N0:219}. Preferably, hybridization occurs under stt~tgent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecute comprising DNA having at least about 80% sequence identity, preferably at least about 85%~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%u sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human pronein cDNA in ATCC
Deposit No. 203246 (DNA66526-1616), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature golypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203246 (DNA66526-1616).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, mast preferably at least about 95% sequence identity to the sequence of amino acid residues from about 28 to about 20I, inclusive of Figure 126 (SEQ ID
N0:220), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a :PR01382 polypeptide having the sequence of amino acid residues from about 28 to about 201, inclusive of Figure 126 (SEQ
ID N0:220), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01382 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position I through about amino acid position 27 in the sequence of Figure 126 (SEQ ID
N0:220).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 28 to about 201, inclusive of Figure 126 (SEQ
ID N0:220}, or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01382 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PROI382 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined. .
In a specific aspect, the invention provides isolated native sequence PR01382 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 28 to 20I of Figure 126 (SEQ ID N0:220).
In another aspect, the invention concerns an isolated PROll382 poIypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably ;at least about 85 % sequence identity, more preferably at Least about 90% sequence identity, most preferably .at least about 95% sequence identity to the sequence of amino acid residues 28 to about 201, inclusive of Figure 126 (SEQ
ID N0:220).
In a further aspect, the invention concerns an isolated PRO:1382 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 28 to 201 of Figure 126 (SEQ ID N0:220).
In yet another aspect, the invention concerns an isolated PR01382 poiypeptide, comprising the sequence of amino acid residues 28 to about 201, inclusive of Figure I26 (SEQ ID
N0:220), or a fragment thereof sufficient to provide a binding site for an anti-PR01382 antibody. Preferably, the PR01382 fragment retains a qualitative biological activity of a native PR01382 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
WO 00/12708 PCT/US99/20I i 1 molecule under stringent conditions with (a) a DNA molecule encoding a PR01382 polypeptide having the sequence of amino acid residues from about 28 to about 20i, inclusive of Figure 126 (SEQ ID N0:220), or (b) the complement of the DNA molecule of (a), and if the test DNA. molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, rttore preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01382 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01382 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01382 polypeptide, by contacting the native PR01382. polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01382 poiypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
64. PR01328 A cDNA clone (DNA66658-1584) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PROI328".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01328 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01328 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID
N0:225), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROI328 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 9 or about b6 and about '779, inclusive, of Figure 127 (SEQ ID N0:224). Preferably, hybridization occurs under stringent hybridization and wash conditions.
Fn a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203229 (DNA66658-1584) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203229 (DNA66658-1584).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a} DNA
encoding a polypeptide having at least about 80 % sequence identin,~, preferably at least about 85 % sequence identity; more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to~ about 257, inclusive of Figure 128 (SEQ ID
N0:225); or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 475 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01328 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID N0:22S), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identit;r, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specif c aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01328 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e.; transmembrane domain deleted or inactivated va~ciants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 128 (SEQ
ID N0:225). The transmembrane 1 S domains have been tentatively identified as extending from about amino acid position 32 to about amino acid position 51, from about amino acid position 119 to about amino acid position 138, from about amino acid position 152 to about amino acid position 169 and from about a~~nino acid position 216 to about amina acid position 235 in the PR01328 amino acid sequence (Figure 128, SEQ ID N0:225).
In another aspect, the invention concerns an isolated nucleic acid. molecule comprising (a) DNA
20 encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID N0:225), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01328 polypeptide coding sequence that may find 25 use as hybridization probes. Such nucleic acid fragments are from. about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, mare preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure I27 (SEQ ID N0:224).
In another embodiment, the invention provides isolated PR01328 polypeptide encoded by any of the 30 isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01328 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 257 of Figure 128 (SEQ ID N0:225).
In another aspect; the invention concerns an isolated PR01:328 poIypeptide, comprising an amino acid 35 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID N0:225).
WO 00/12708 PCT/US99120i 11 In a further aspect, the invention concerns an isolated PRO 1328 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID
N0:225).
In yet another aspect, the invention concerns an isolated PR01328 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 257, inclusive of Figure i28 (SEQ ID N0:225), or a fragment thereof sufficient to provide a binding site for an anti-PRO1328 <uttibody.
Preferably, the PRO1328 fragment retains a qualitative biological activity of a native PR01328 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1328 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 257, inclusive of Figure 128 (SEQ ID
N0:225), or (b) the complement of the DNA molecule of (a}, arid if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequE;nce identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
65. PR01325 A cDNA clone (DNA66659-1593} has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PROI32S".
In one embodiment, the invention provides an isolated nu<;leic acid molecule comprising DNA encoding a PR01325 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 %a sequence identity to {a) a DNA molecule encoding a PRO 1325 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID
N0:227}, or (b} the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01325 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 51 or about 105 and about 2546, inclusive, of Figure 129 {SEQ ID N0:226).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect; the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203269 (DNA66659-1593) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203269 (DNA66659-1593).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID
N0:227), or (b) the complement of the DNA of (a}.
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least I00 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01325 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID N0:227), or (b) the c:ornplement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01325 poiypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding IS nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position l8 in the sequence of Figure;130 (SEQ
ID N0:227). The transmembrane domains have been tentatively identified as extending from about amino acid position 292 to about amino acid position 3I7, from about amino acid position 451 to about amino acid position 470, from about amino acid position SOI to about amino acid position 520, from about amino acid position 607 to about amino acid position 627 and from about amino acid position 751 to about amino aciid position 770 in the PR01325 amino acid sequence (Figure I30, SEQ ID N0:227).
Tn another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID N0:227), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01325 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 129 (SEQ ID N0:226).
In another embodiment, the invention provides isolated fR01325 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01325 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues I or about 19 to about 832 of Figure 130 (SEQ ID N0:227).
In another aspect, the invention concerns an isolated PR01325 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at Ieast about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about -I9 to about 832, inclusive of Figure 130 (SEQ ID N0:227).
In a further aspect, the invention concerns an isolated PR01325 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least ;about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives 'when compared with the amino acid sequence of residues 1 or about 39 to about 832, inclusive of Figure 130 {SEQ ID
N0:227).
In yet another aspect, the invention concerns an isolated PFt01325 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 832, inclusive of Figure 130 (SEQ ID N0:227), or a fragment thereof sufficient to provide a binding site for an anti-PR01325 antibody.
Preferably, the PR01325 fragment retains a qualitative biological activity of a native PR01325 polyFreptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with {a) a DNA molecule encoding a PR01325 polypeptide having the sequence of amino acid residues from about 1 or about 19 to albout 832, inclusive of Figure 130 (SEQ ID
N0:227), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
66. PR01340 A cDNA clone (DNA66663-1598) has been identified that encodes a novel polypeptide having homology to Ksp-cadherin and designated in the present application as "PR0~1340."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01340 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably .at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01344 polypepiide having the sequence of amino acid residues from 1 or about 19 to about 807, inclusive of Figure 132 (SEQ ID N0:229), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1340 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 182 and about 2548, inclusive, of Figure 131 (SEQ ID N0:228). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85%a sequence identity, wore preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203268 (DNA66663-1598}, or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203268 (DNA66663-1598).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 (SEQ ID
N0:229), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule IO under stringent conditions with {a) a DNA molecule encoding a fR01340 polypeptide having the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 (SEQ
ID N0:229); or (b} the complement of the DNA molecule of (a), and, if the DNA molecul'.e has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01340 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. iransmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively iderxtified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure :132 (SEQ ID
N0:229). The transmembrane domain has been tentatively identified as extending from about amino acid position 762 to about amino acid position 784 in the PR01340 amino acid sequence (Figure 132, S.EQ ID N0:229).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at Least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 807, inclusive of Figure 132 (SEQ
ID N0:229), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01340 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length,. and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01340 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1340 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 to 807 of Figure 132 (SEQ ID N0:229).
In another aspect, the invention concerns an isolated PRO1340 polypepdde, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the WO 00/12708 PCTlUS99I20111 sequence of amino acid residues 19 to about 807, inclusive of Figure 132 (SEQ
ID N0:229).
In a further aspect, the invention concerns an isolated PR01340 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, .most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 to 807 of Figure 132 (SEQ ID N0:229).
In yet another aspect, the invention concerns an isolated PR01340 polypeptide, comprising the sequence of amino acid residues 19 to about 807, inclusive of Figure 132 (SEQ ID
N0:229), or a fragment thereof sufficient to provide a binding site for an anti-PR01340 antibody. Preferably, the PR01340 fragment retains a qualitative biological activity of a native PR01340 polypeptide.
In a still further aspect, the invention provides a polypehtide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01340 polygeptide having the sequence of amino acid residues from about 19 to about 807, inclusive of Figure 132 {SEQ ID N0:229), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to {a) or {b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PRO1340 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01340 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI340 polypeptide, by contacting the native PR01340 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1340 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
67. PR01339 A cDNA clone (DNA66669-1597) has been identified that encodes a novel polypeptide having sequence identity with carboxypepsidases and designated in the present application as "PR01339."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01339 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01339 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 421, inclusive of Figure 134 (SEQ ID N0:234), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01339 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 58 and about 1271, inclusive, of Figure 133 (SEQ ID N0:233): Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, mare preferably at least about 90% sequence identity, most preferably at least about 95 %a sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203272 (DNA66669-1597), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203272 (DNA66669-1597).
In a still further aspect, the invention concerns an isolated nucieic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % ~ sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 17 to about 421, inclusive of Figure 134 (SEQ ID
N0:234), or the complement of the DNA of (a):
In a further aspect, the invention concerns an isolated nuicleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01339 polypeptide having the sequence of amino acid residues from about 17 to about 421, inclusive of Figure 134 (SEQ
ID N0:234), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a} or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 17 to about 42I, inclusive of Figure 134 (SEQ
ID N0:234), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01339 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from. about 20 to about 80 nucleotides in length, preferably from about 20 to about.60 nucleotides in length, mine preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about ~40 nucleotides in length.
In another embodiment, the invention provides isolated Plft01339 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PROI339 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 17 through 421 of Figure 134 (SEQ ID
N0:234).
In another aspect, the invention concerns an isolated PROI339 polypeptide;
comprising an amino acid sequence having at least about 80 % sequence identity, preferably ait least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably a,t least about 95% sequence identity to the sequence of amino acid residues 17 to about 421, inclusive of Figure 134 (SEQ
ID N0:234).
In a further aspect, the invention concerns an isolated PRC) 1339 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues i7 through 421 of Figure 134 (SEQ ID N0:234).
in yet another aspect; the invention concerns an isolated PP;O 1339 polypeptide, comprising the sequence of amino acid residues 17 to about 421, inclusive of Figure 1346 (SEQ ID
N0:234), or a fragment thereof sufficient to provide a binding site for an anti-PR01339 antibody., Preferably, the PR01339 fragment retains a qualitative biological activity of a native PR01339 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01339 polypeptide having the sequence of amino acid residues from about 17 to about 421, inclusive of Figure i34 (SEQ ID N0:234), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01339 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01339 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01339 polypeptide, by contacting the native PR01339~ polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1339 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
68. PR01337 A cDNA clone (DNA66672-i586)has been identified that encodes a novel polypeptide having homology to huunan thyroxine-binding globulin designated in the present application as "PR01337".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROi337 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferable at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01337 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 41'7, inclusive of Figure 136 (SEQ ID N0:236), or (b} the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01337 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 120 and about 1310, inclusive, of Figure 135 (SEQ ID N0:235). Preferably, hybridization occurs tinder stringent hybridization and wash conditions. ' WO 00!12708 PCT/US99/20111 In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85°o sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 ',~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203265 (DNA66672-66672), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, rite nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203265 (DNA66672-66672).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to ;shout 417, inclusive of Figure 136 (SEQ ID
N0:236), or the complement of the DNA of (a):
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides; and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01337 polypeptide having the sequence of amino acid residues from about 21 to about 417, inclusive of Figure 136 (SEQ
ID N0:236), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nuclleic acid molecule comprising DNA encoding a PR01337 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position I through about amino acid position 20 in the sequence of Figure 136 (SEQ
ID N0:236).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, prt;ferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 21 to about 417, inclusive of Figure 136 (SEQ
ID N0:236), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 13:37 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, snore preferably from about 20 to almut 50 nucleotides in length, and most preferably from about 20 to about. 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01337 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01337 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 417 of Figure 136 (SEQ ID N0:236).
In another aspect, the invention concerns an isolated PR0~1337 polypeptide, comprising an amino acid 176 .
WO 00!12708 PCT/US99/20111 sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 21 to about 417, inclusive of Figure 136 (SEQ
ID N0:236).
In a further aspect, the invention concerns an isolated PRO 1337 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 417 of Figure 136 {SEQ ID N0:236).
in yet another aspect, the invention concerns an isolated PRO i 337 poiypeptide, comprising the sequence of amino acid residues 21 to about 417, inclusive of Figure I3~6 (SEQ ID
N0:236), or a fragment thereof sufficient to provide a binding site for an anti-PR01337 antibody. Preferably, the PR01337 fragment retains a qualitative biological activity of a native PR01337 polypeptide.
In a still further aspect, the invention provides a polypelnide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01337 polypeptide having the sequence of amino acid residues from about 21 to about 417, inclwive of Figure 136 {SEQ ID N0:236), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to {a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the celi culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01337 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01337 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI337 polypeptide, by contacting the native PR01337 polypeptide with a candidate molecule and monitoring; a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO1337 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
69. PRO1342 A cDNA clone (DNA66674-1599) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PROI342".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01342 polypeptide.
in one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01342 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 59fi, inclusive of Figure 138 (SEQ ID N0:243), or (b) the complement of the DNA mol~ule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01342 WO OOII2?08 PCT/US99/20111 polypeptide comprising DNA hybridizing to the complement of the: nucleic acid between about residues 299 and about 2026, inclusive, of Figure 137 (SEQ ID N0:242). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 °a sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203281 (DNA66674-1599), or (b) the complement of the DNA molecule of (a). In a preferred embodiment; the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203281 (DNA66674-1599).
In a still farther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to .about 596, inclusive of Figure 138 (SEQ ID
N0:243), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01342 polypeptide having the sequence of amino acid residues from about 21 to about 596, inclusive of Figure 138 (SEQ
ID N0:243), or (b) the complement of the DNA molexule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a speck aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI342 polypepdde, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 138 (SEQ ID
N0:243): The transmembrane domain has been tentatively identified as extending from about amino acid position 510 to about amino acid position 532 in the PR01342 amino acid sequence (Figure 138, SEQ ID N0:243).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least at~out 95%
positives when compared with the amino acid sequence of residues 21 to about 596, inclusive of Figure 138 (SEQ
ID N0:243), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01342 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
WO 00/12708 PCTlUS99/20111 In another embodiment, the invention provides isolated P~R01342 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specificaspect, the invention provides isolated native sequence PR01342 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 596 of Figure 138 (SEQ ID N0:243).
In another aspect, the invention concerns an isolated PR01342 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 596, inclusive of Figure 138 (SEQ
ID N0:243).
In a further aspect, the invention concerns an isolated PRCI1342 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives vvhen compared with the amino acid sequence of residues 21 to 596 of Figure i38 (SEQ ID N0:243).
In yet another aspect, the invention concerns an isolated PR01342 polypeptide, comprising the sequence of amino acid residues 21 to about 596, inclusive of Figure 138 (SEQ ID
N0:243), or a fragment thereof sufficient to provide a binding site for an anti-PR01342 antibody. Preferably, the PR01342 fragment retains a qualitative biological activity of a native PR01342 polypeptide.
In a still further aspect, the invention provides a polypep~tide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01342 polypeptide having the sequence of amino acid residues from about 21 to about 596, inclusive of Figure 138 (SEQ ID N0:243), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
70. PR0134 A cDNA clone (DNA66675-1587) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01343".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI343 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA :having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01343 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID
N0:248), or (b} the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01343 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 71 or about 146 and about 811, inclusive, of Figure 139 (SEQ ID N0:247).
Preferably, hybridization occurs under WO OO1i2708 PCT/US99/20111 stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 8:i %
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature poiypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203282 (DNA66675-1587) or {b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polype:ptide encoded by the human protein cDNA in ATCC Deposit No. 203282 (DNA66675-1587).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID
NO:248), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule; under stringent conditions with (a) a DNA
molecule encoding a PR01343 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID N0:248), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01343 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 140 (SEQ
ID N0:248).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at feast about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 247, inchisive of Figure 140 (SEQ ID N0:248), or (b) the complement of the DNA of (a}.
Another embodiment is directed to fragments of a PRO 1:343 polypeptide coding sequence that rnay find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, raore preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 139 (SEQ ID N0:247).
In another embodiment, the invention provides isolated PR01343 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01343 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 247 of Figure 140 (SEQ ID N0:248).
In another aspect, the invention concerns an isolated PRO1343 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 247, inclusive of Figure 140 (SEQ ID N0:248).
In a further aspect, the invention concerns an isolated PRIJ1343 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues i or about 26 to about 247, inclusive of Figure 140 (SEQ ID
N0:248).
In yet another aspect, the invention concerns an isolated P1~01343 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 247, inclusive of higure 140 (SEQ ID N0:248), or a fragment thereof sufficient to provide a binding site for an anti-PR01343 antibody.
Preferably, the PR01343 fragment retains a qualitative biological activity of a native PR01343 polypeptide.
In a still further aspect, the invention provides a polype~ptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01343 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 247, inclusive of Figure 140 (SEQ iD
N0:248}, or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequc;nce identity, more preferably at least about a 90 % sequence identity, most preferably at Least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable: for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
71. PR01480 A cDNA clone (DNA67962-1649) has been identified that encodes a novel polypeptidehaving homology to Semaphorin C and designated in the present application as "PR01480."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01480 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferable at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01480 polypeptide having the sequence of amino acid residues from about 1 to about 837, inclusive of Figure 142 (SEQ ID N0:253), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01480 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 241 and about 2751, inclusive, of Figure 141 (SEQ ID N0:252}. Prefe;rably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 ',~o sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ro sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203291 (DNA67962-1649), or (6) the complement of the DNA molecule o:f (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203291 (DNA67962-1649).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, nnost preferably at least about 95% sequence identity to the sequence of amino acid residues from about i to about 837, inclusive of Figure 142 (SEQ ID
N0:253), or the complement of the DNA of {a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01480 polypeptide having the sequence of amino acid residues from about 1 to about 837, inclusive of lFigure 142 {SEQ
ID N0:253), or (b) the complement of the DNA molecule of {a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to {a) or (b), iscdating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01480 polypeptide, its soluble variants, {i.e. txansmembrane domains deleted or inactivated) or is complementary to such encoding nucleic acid molecule. Transmembrane domains have been tentatively identified as extending from about amino acid position 23 to about amino acid position 46 (type II) and about amino acid position 718 to about amino acid position 738 in the PR01480 amino acid sequence (Figure 142, SEQ ID N0:253).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 837, inclusive of Figure 142 {SEQ
ID N0:253), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01480 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated F'R01480 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01480 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 837 of Figure 142 (SEQ ID N0:253).
In another aspect, the invention concerns an isolated PRO 1480 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 837, inclusive of Figure 142 (SEQ
ID N0:253).
In a further aspect, the invention concerns an isolated PR01480 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 837 of Figure 142 (SEQ ID N0:253).
In yet another aspect, the invention concerns an isolated PRO 1480 polypeptide, comprising the sequence of amino acid residues I to about 837, inclusive of Figure 142 (SEQ ID
N0:253), or a fragment thereof sufficient to provide a binding site for an anti-PR01480 antibody. Preferably, the PR01480 fragment retains a qualitative biological activity of a native PR01480 polypeptide.
In a still further aspect, the invention provides a polypep~tide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01480 polypeptide having the sequence of amino acid residues from about 1 io about 837, inclusive of Figure 142 {SEQ ID N0:253), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to !;a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns ago~austs and antagonists of a native PR01480 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01480 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01480 polypeptide, by contacting the native PR01480 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1480 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
72. PR0148'7 A cDNA clone {DNA68836-1656) has been identified that c;ncodes a novel polypeptide havinghomology to fringe protein and designated in the present application as "PR01487"'.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01487 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA raving at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01487 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 802, inclusive of Figure 144 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a).
In another aspect; the invention concerns an isolated nucleic acid molecule encoding a PR01487 WO 00112708 PCT/US99l20111 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 558 and about 2894, inclusive, of Figures 143A-B (SEQ ID N0:259). Prelferably, hybridization occurs under stringent hybridization and wash conditions.
In a farther aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 %~ sequence identity to (a) a DIVA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203455 (DNA68836-1656), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203455 (DNA68836-1656).
In a still further aspect, the invention concerns an isolated. nucleic acid molecule comprising (a) DNA
encoding a poiypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 144 (SEQ ID
N0:260), or the complement of the DNA of (a).
IS In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PP',01487 polypeptide having the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 144 (SEQ
ID N0:260), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding . a PR01487 polypeptide, with or without the N-terminal signal sequence and/or the initiating, or is complementary to such encoding nucleic acid molecule. The sigxuil peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 144 (SEQ
ID N0:260).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, prefi~rably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 24 to about 802, inclusive of Figure 144 (SEQ
ID N0:260), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01487 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from abut 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR.01487 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO1487 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 to 802 of Figure 144 (SEQ ID N0:260).
In another aspect, the invention concerns an isolated PR01487 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 802, inclusive of Figure 144 (SEQ
ID N0:260).
In a farther aspect, the invention concerns an isolated PR01487 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 to 802 of Figure 144 (SEQ ID N0:260).
In yet another aspect, the invention concerns an isolated PRO 1487 polypeptide, comprising the sequence of amino acid residues 24 to about 802, inclusive of Figure 14.4 (SEQ ID
N0:260), or a fragment thereof sufficient to provide a binding site for an anti-PR01487 antibody. Preferably, the PR01487 fragment retains a qualitative biological activity of a native PR01487 polypeptidc.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01487 polypeptide having the sequence of amino acid residues from about 24 to about 802, inclusive of Figure 14.4 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, mare preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01487 polypeptide: In a particular embodiment, the agonist or antagonist is an anti-PR01487 antibody.
In a further embodiment, the invention concerns a meth<xi of identifying agonists or antagonists of a native PR01487 polypeptide, by contacting the native PRO1487 polypeptide with a candidate molecule and monitoring a biological activity mediated by said poIypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1487 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
73. PIt01418 A cDNA clone (DNA68864-1629) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01418."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01418 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably .at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01418 polypeptide having the sequence of amino acid residues from I or about 20 to about 350, inclusive of Figure 146 {SEQ ID N0:265), or (b) the complement of the DNA molecule of {a).
In another aspect, the invention concerns an isolated ;nucleic acid molecule encoding a PR01418 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 195 and about 1187, inclusive, of Figure 145 (SEQ ID N0:264). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203276 (DNA68864-1629), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203276 (DNA68864-1629).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence idenl:ity, preferably at least about 85% sequence i5 identity, more preferably at least about 90% sequence identity, nnost preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 350, inclusive of Figure 146 (SEQ ID
N0:265), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PlIt01418 polypeptide having the sequence of amino acid residues from about 20 to about 350, inclusive of .Figure 146 (SEQ
ID N0:265), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity; more preferably at least about a 90 % sequence identity, most preferably at Least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 20 to about 350, inclusive of Figure I46 (SEQ
ID N0:265), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI41;B polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01418 polypeptide encoded by arty of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01418 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 350 of Figure 146 (SEQ ID
N0:265).
In another aspect, the invention concerns an isolated PR01418 poIypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 20 to about 350, inclusive of Figure 146 (SEQ
ID N0:265).
In a further aspect, the invention concerns an isolated PR01418 polypegtide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 350 of Figure 146 (SEQ ID N0:265).
In yet another aspect, the invention concerns an isolated PR01418 polypeptide, comprising the sequence IO of amino acid residues 20 to about 350, inclusive of Figure 146 (SEQ ID
N0:265), or a fragment thereof sufficient to provide a binding site for an anti-PROi418 antibody. Preferably, the PR01418 fragment retains a qualitative biological activity of a native PR01418 polypeptide.
In a still further aspect, the invention provides a poiypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR014i8 polypeptide having the IS sequence of amino acid residues from about 20 to about 350, inclusive of Figure 146 (SEQ ID N0:265), or (b) the complement of the DNA molecule of (a), and if the test DNA :molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and {iii) recovering the 20 polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonnsts and antagonists of a native PR01418 polypeptide. In a particular embodiment, the agonist or antagonist is an and-PR014i8 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROi418 polypeptide, by contacting the native PR01418 ;polypeptide with a candidate molecule and 25 monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROi418 polypeptide, or an agonist ar antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
74. PR01472 30 A cDNA clone (DNA68866-1644) has been identified that encodes a novel polypeptide having sequence identity with butyrophilin and designated in the present application as "PROi472."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01472 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 35 preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1472 polypeptide having the sequence of amino acid residues from i or about 18 to about 466, :inclusive of Figure 148 (SEQ ID N0:267), or (b) the complement of the DIVA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01472 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 185 and about 1531, inclusive, of Figure 147 (SEQ ID N0:266). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nL~cleic acid molecule comprising DNA having at least about 80% sequence identity, preferabiy,at least about 85'% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203283 (DNA68866-1644), or (b) the complement of the DNA molecule o:f (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No: 203283 (DNA68866-1644).
In a still former aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to alwut 466, inclusive of Figure 148 {SEQ ID
N0:267), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01472 polypeptide having the sequence of amino acid residues from about 18 to about 466, inclusive of Figure 148 (SEQ
ID N0:267), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01472 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 1-17 in the sequence of Figure 14:8 (SEQ
ID N0:267). The transmembrane domains have been tentatively identified as being from about amino acid position I3I through about amino acid position 150 and from about amino acid position 235 through about amino acid position 259 in the PR01472 amino acid sequence (Figure 148, SEQ ID N0:267). It is understood that PR01472 can be manipulated to contain only particular regions given the information herein, e.g. to have only the extracellular or cytoplasmic regions only, or to have the carboxyl end truncated wherein the second transmembrane domain is deleted.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 18 to about 466, inclusive of Figure 148 (SEQ
ID NO:267), or {b) the 18$
complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI472 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides, isolated PRO 1472 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01472 polypeptide, which in one embodiment, includes an amino acid sequence comprising residlues 18 through 466 of Figure 148 (SEQ ID
N0:267).
In another aspect, the invention concerns an isolated PR01472 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 466, inclusive of Figure 148 (SEQ
ID N0:267).
In a further aspect, the invention concerns an isolated PRIJ 1472 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least .about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 through 466 of Figure 148 (SEQ ID N0:267).
In yet another aspect, the invention concerns an isolated PF;O 1472 polypeptide, comprising the sequence of amino acid residues 18 to about 466, inclusive of Figure 14E~ (SEQ ID
N0:267), or a fragment thereof sufficient to provide a binding site for an anti-PR01472 antibody. Preferably, the PR01472 fragment retains a qualitative biological activity of a native PR01472 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i} hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01472 polypeptide having the sequence of amino acid residues from about 18 to about 466, inclu;>ive of Figure 148 (SEQ ID N0:267), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (;a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01472 polypeptade. In a particular embodiment, the agonist or antagonist: is an anti-PR01472 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PROI472 polypeptide, by contacting the native PR01472 ~oolypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01472 polypeptide, or an agonist or antagonist as hereinabove defined, in combination 'with a pharmaceutically acceptable carrier.
WO OO/I2708 PCTlUS99120111 75. PR01461 A cDNA clone (DNA688? 1-I638) has been identified that encodes a novel polypeptidehaving homology to serine protease and designated in the present application as "PR01461".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01461 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01461 polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of Figure i50 (SEQ ID N0:269), or (b) the complement of the DNA molecule of (a). -In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01461 palypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 32 and about 1300, inclusive, of Figure 149 (SEQ ID N0:268). Pre:ferabIy, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at Least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203280 (DNA68871-68871), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203280 (DNA68871-68871).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID
N0:269), or the complement of the DNA of {a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P.RO1461 polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of 1~igure I50 (SEQ
ID N0:269), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01461 polypeptide, with or without the initiating meihionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. A type II
transmembrane domain has been tentatively identified as extending from about amino acid position 21 to about amino acid position 40 in the PR01461 amino acid sequence (Figure 150, SEQ ID
N0:269).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues I to about 423, inclusive of Figure 150 (SEQ
ID N0:269), or {b) the complement of the DNA of {a).
Another embodiment is directed to fragments of a PROI4.61 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1?R01461 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01461 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 423 of Figure 150 (SEQ ID N0:269).
In another aspect, the invention concerns an isolated PR0~1461 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about $5% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 423, inclusive of Figmre 150 (SEQ
ID N0:269).
In a further aspect, the invention concerns an isolated PRO~I461 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least albout 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to 423 of Figure I50 (SEQ ID N0:269}.
In yet another aspect, the invention concerns an isolated PRO1461 polypegtide, comprising the sequence of amino acid residues 1 to about 423, inclusive of Figure 150 (SEQ ID
N0:269), or a fragment thereof sufficient to provide a binding site for an anti-PR01461 antibody. Preferably, the PR01461 fragment retains a qualitative biological activity of a native PR01461 polypeptide.
In a still further aspect, the invention provides a polypepti.de produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a} a DNA molecule encoding a PR01461 polypeptide having the sequence of amino acid residues from about 1 to about 423, inclusive of Figure 150 (SEQ ID N0:269), or (b) the complement of the DNA molecule of (a), and if the test DNA miolecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a;l or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01461 polypeptide. In a particular embodiment, the agonist or antagonist :is an anti-PR0146i antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01461 polypeptide, by contacting the native PR01461 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
WO 00/12708 PCT/US99120i11 In a still further embodiment, the invention concerns a composition comprising a PRO 1461 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
76. PR014I0 A cDNA clone (DNA68874-1622) has been identified that encodes a novel transmembrane polypeptide, S designated in the present application as "PR01410".
In one embodiment, the invention provides an isolated nu<;leic acid molecule comprising DNA encoding a PR01410 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01410 polypeptide having the sequence of annino acid residues from about 1 or about 2I to about 238, inclusive of Figure 1S2 (SEQ ID
N0:271), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01410 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 1S2 1 S or about 212 and about 865, inclusive, of Figure 1S 1 (SEQ ID N0:2?0).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203277 (DNA68874-1622) or (b) the complement of the nucleic acid molecule of {a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203277 (DNA68874-1622).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
2S encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID
N0:271), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with {a) a DNA
molecule encoding a PR01410 polypeptide having the sequence of amino acid residues from i or about 21 to about 238, iztclusive of Figure 1S2 (SEQ ID N0:271), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S % sequence 3S identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01410 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 152 (SEQ
ID N0:271). The transmembrane domain has been tentatively identified as extending from about. amino acid position 194 to about amino acid position 220 in the PR01410 amino acid sequence (Figure 152, SEQ ID N0:271).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 21 to about 238, inclusive of Figure I52 (SEQ ID N0:271), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01410 poIypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, snore preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about: 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 151 (SEQ ID N0:2?0).
In another embodiment, the invention provides isolated PR01410 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01410 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 238 of Figure 152 (SEQ ID N0:271).
In another aspect, the invention concerns an isolated PRO1410 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID N0:271}.
In a further aspect, the invention concerns an isolated PR0~1410 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 238, inclusive of Figure I52 (SEQ ID
N0:271).
In yet another aspect, the invention concerns an isolated PR01410 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 238, inclusive of Figure 152 (SEQ ID N0:271), or a fragment thereof sufficient to provide a binding site for an anti-PR01410 antibody.
Preferably, the PR01410 fragment retains a qualitative biological activity of a native PR01410 polypE;ptide.
In a still further aspect, the invention provides a poIypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01410 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 238, inclusive of Figure 152 {SEQ ID
N0:271), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable far expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01410 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01410 antibody.
1n a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01410 polypeptide by contacting the native PR01410 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR014I0 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
77. PR 1568 A cDNA clone (DNA68880-1676) has been identified that encodes a novel polypeptide having sequence identity with tetraspanins and designated in the present application as "PR01568."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01568 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably .at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01568 polypeptide having the sequence of amino acid residues from 1 or about 34 to about 305, inclusive of Figure 154 (SEQ ID N0:273), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1568 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 307 and about 1122, inclusive, of Figure 153 (SEQ ID N0:272). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203319 (DNA68880-1676), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203319 (DNA6888(?-1676).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about $0% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ ID
N0:273), or the complement of the DNA of (a).
1n a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about I00 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI568 polypeptide having the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ
ID N0:273), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 %. sequence identity, more preferatdy at lease about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01568 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 33 in the sequence of Figure 154 (SEQ ID
N0:273). The transmembrane domains have been tentatively identified as extending from about aunino acids 12-35, 57-86, 94-114 and 226-248 in the PR01568 amino acid sequence (Figure i54, SEQ ID N0::273).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a} DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 34 to about 305, inclusive of Figure 154 (SEQ
ID N0:273), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1568 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01568 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1568 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 34 through 305 of Figure 154 (SEQ ID
N0:273).
In another aspect, the invention concerns an isolated PR01568 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 34 to about 305, inclusive of Figure 154 (SEQ
ID N0:273}.
In a further aspect, the invention concerns an isolated PR0~1568 polypeptide, comprising an amino acid sequence scoring at least about $0% positives, preferably at least albout 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 34 through 305 of Figure 154 (SEQ ID N0:273).
In yet another aspect, the invention concerns an isolated PRO1568 polypeptide, comprising the sequence of amino acid residues 34 to about 305, inclusive of Figure 154 (SEQ ID
N0:273), or a fragment thereof sufficient to provide a binding site for an anti-PR01568 antibody. Preferably, the PR01568 fragment retains a qualitative biological activity of a native PR01568 polypeptide.
In a soil farther aspect, the invention provides a polyp~eptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01568 polypeptide having the sequence of amino acid residues from about 34 to about 305, inclusive of Figure 154 (SEQ ID N0:273), or (b}
the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at Least about a 90% sequence S identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerxts agoxtists and antagoxtists of a native PR01568 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01568 antibody.
In a further embodiment, the invention concerns a method of identifying agoxtists or antagonists of a native PR01568 polypeptide, by contacting the native PR0156Ig polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a coxnposition comprising a PRO 1568 polypeptide, or an agonist or antagonist as hereixtabove defined, in combination with a pharmaceutically acceptable carrier.
78. PROI570 A cDNA clone (DNA68885-1678) has been identified that encodes a novel polypeptide having sequence identity with SP60 and designated in the present application as "PR01570." In particular, for the first time, Applicants have identified an additional 199 amino acids on the stmino terminal end of the protein previously identified as SP60.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01570 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most 2S preferably at least about 95 % sequence identity to {a) a DNA molecule encoding a PR01570 polypeptide having the sequence of amino acid residues from about i to about 432, inclusive of Figure 156 (SEQ ID N0:275), or (b) the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01570 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 210 and about 1505, inclusive, of Figure I55 (SEQ ID N0:274). Preferably, hybridization occurs under stringent hybridization and wash conditioxts.
1n a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 %. sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 %~ sequextce identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203311 (DNA68885-1678), or (b) the complement of the DNA molecule of (a), In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203311 (DNA68885-1678).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about i to~ about 432, inclusive of Figure 156 (SEQ ID
N0:275), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and p~rodueed by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01570 polypeptide having the sequence of amino acid residues from about 1 to about 432, inclusive of Figure 156 (SEQ ID
N0:275), or (b) the complement of the DNA molecule of (a), and, if the DNA moIecnhe has at least about an 80 % sequence identity, preferably at Feast about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule. In a preferred embodiment, the probes provided herein are from the amino terminal end of the peptide identified in Figure 1, defined as amino acids i-199 of SEQ ID N0:275.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01570 polypeptide, in a form which is secreted and is soluble, i.e.
transmembrane domain deleted, truncated or inactivated variants.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 432, inclusive of Figure 156 (SEQ
ID N0:275), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01570 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length. Preferably, the probes are from the amino terminal end as provided herein.
In another embodiment, the invention provides isolated PR01570 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PROi570 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 432 of Figure 156 (SEQ ID
NO:Z75).
In another aspect, the invention concerns an isolated PR01570 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 432, inclusive of Figure. i56 (SEQ
ID N0:275).
in a farther aspect, the invention concerns an isolated PRO 1570 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 432 of Figure 156 (SEQ ID N0:275).
In yet another aspect, the invention concerns an isolated PRO 1570 polypeptide, comprising the sequence of amino acid residues 1 to about 432, inclusive of Figure 156 (SEQ ID
N0:275), or a fragment thereof sufficient to provide a binding site for an anti-PR01570 antibody. Preferably, the PR01570 fragment retains a qualitative biological activity of a native PR01570 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROi570 polypeptide having the sequence of amino acid residues from about 1 to about 432, inclusive of Figure 156 (SEQ ID N0:275), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to 1',a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
1~ In yet another embodiment, the invention concerns agonists and antagonists of a native PR01570 poiypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01570 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01570 polypeptide, by contacting the native PR01570 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROi570 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
79. PR 1317 A cDNA clone {DNA7I 166-1685) has been identified that encodes a novel polypeptidehaving homology to semaphorin B and designated in the present application as "PRG1317".
In one embodiment, the invention provides an isolated nucleic acid moiecule comprising DNA encoding a PR013I7 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably ;at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1317 poiypeptide having the sequence of amino acid residues from 1 or about 31 to about 761, inclusive of Figure 158 (SEQ ID N0:277), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1317 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 195 and about 2387, inclusive, of Figure 157 (SEQ ID N0:276). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having WO 00/12708 pCTlUS99120111 at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203355 (DNA71166-1685), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203355 (DNA71166-1685).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about $0% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 158 (SEQ ID
N0:277), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a Lest DNA molecule under stringent conditions with (a) a DNA molecule encoding a P~ROI317 polypeptide having the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 158 (SEQ
ID N0:277), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01317 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 158 (SEQ ID
N0:277). Transmembrane domains have been tentatively identified as extending from about amino acid positions I3-31, 136-156, 222-247, 474-490, and 685-704 in the PROI31? amino acid sequence (Figure 158, SEQ ID
N0:277).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 31 to about 761, inclusive of Figure 158 (SEQ
ID N0:277), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01317 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01317 polypeptide encoded by any of the 3S isolated nucleic acid sequences hereinabove defined.
In a specific as~ct, the invention provides isolated native sequence PR01317 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 761 of Figure 158 (SEQ ID N0:277).
In another aspect, the invention concerns an isolated PRO 1317 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 31 to about 761, inclusive of Figure 1S8 (SEQ
ID N0:277).
In a further aspect, the invention concerns an isolated PROI317 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 31 to 761 of Figure 1S8 (SEQ ID N0:277).
In yet another aspect, the invention concerns an isolated PROl 317 polypeptide, comprising the sequence of amino acid residues 31 to about 761, inclusive of Figure IS8 (SEQ ID
N0:277),.or a fragment thereof sufficient to provide a binding site for an anti-PROI317 antibody. Preferably, the PR01317 fragment retains a qualitative biological activity of a native PR01317 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01317 polypeptide having the sequence of amino acid residues from about 31 to about 761, inclusive of Figure 1S8 (SEQ ID N0:277), or (b) 1S the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 8S % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poiypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR013I7 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01317 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR013i7 polypeptide, by contacting the native PR01317 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1317 polypeptide, or an agonist or antagonist as hereinabove defined, in combination. with a pharmaceutically acceptable carrier.
80. PR01780 A cDNA clone (DNA71169-1709) has been identif edthat encodes a novel golypeptide having homology to glucuronosyltransferase and designated in the present application as "PR01780".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01780 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PR01780 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 523, inclusive of Figure 160 (SEQ ID N0:282), or (b) the complement of the DNA molecule of (a).
WO 00112708 PCTIUS99l2011 I
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01780 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 125 and about 1636, inclusive, of Figure 159 (SEQ 1D N0:281). Prs;ferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having S at least about 80% sequence identity, preferably at least about 8:5 %
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human lprotein cDNA in ATCC Deposit No. 203467 (DNA7I169-1709), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature- poIypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203467 (DNA71169-1709).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at Least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 523, inclusive of Figure 160 (SEQ ID
I5 N0:282}, or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01780 pol;ypeptide having the sequence of amino acid residues from about 20 to about 523, inclusive of Figure 160 (SEQ ID N0:282), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b),, isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01780 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted ar inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 19 in the sequence of Figure :L60 (SEQ ID
N0:282). The transmembrane domain has been tentatively identified as extending from about amino acid position 483 to about amino acid position 504 in the PR01780 amino acid sequence (Figure 160, SEQ ID N0:282).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 20 to about 523, inclusive of Figure 160 (SEQ
iD N0:282); or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PROI780 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length;
preferably from about 20 to about 60 nucleosides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to at~out 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01780 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01780 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 to 523 of Figure 160 (SEQ ID N0:282).
In another aspect, the invention concerns an isolated PR01780 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 523, inclusive of Figure 160 (SEQ
ID N0:282).
In a further aspect, the invention concerns an isolated PR01780 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 to 523 of Figure 160 (SEQ ID N0:282).
In yet another aspect, the invention concerns an isolated F~R01780 polypeptide, comprising the sequence of amino acid residues 20 to about 523, inclusive of Figure 150 (SEQ ID
N0:282), or a fragment thereof sufficient to provide a binding site for an anti-PR01780 antibody. Preferably, the PR01780 fragment retains a qualitative biological activity of a native PR01780 poIypeptide.
In a still futttter aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01780 polygeptide having the sequence of amino acid residues from about 20 to about 523, inclrtsive of Figure 160 (SEQ ID N0:282), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture:
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01780 polypeptide. In a particular embodiment, the agonist or antagoni st is an anti-PR01780 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01780 polypeptide, by contacting the native PROI780 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1780 polypeptide, or an agotiist or antagotust as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
81. PR01486 A cDNA clone (DNA71180-1655) has been identified that encodes a novel polypeptide having sequence identity with cerebellin, particularly precerebeIlin, and designated in the present application as "PROI486."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01486 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA, having,at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01486 polypeptide having the sequence of amino acid residues from 1 or about 33 to about 205, inclusive of Figure 162 (SEQ ID N0:287), or (b} the complement of the DNA rnolecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01486 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 568 and about 1086, inclusive, of Figure 16i (SEQ ID N0:286). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at Least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203403 (DNA71180-1655), or (b} the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203403 (DNA71180-1655).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 33 to about 205, inclusive of Figure 162 (SEQ ID
N0:287), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated ntu:leic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01486 polypeptide having the sequence of amino acid residues from about 33 to about 205, inclusive of l:~igure 162 (SEQ
ID N0:287), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 33 to about 205, inclusive of Figure 162 (SEQ
ID N0:287), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01486~ polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from .about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01486 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01486 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 33 through 205 of Figure 162 {SEQ ID
N0:287).
In another aspect, the invention concerns an isolated FR01486 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 33 to about 205, inclusive of Figure 162 (SEQ
ID N0:28?).
In a further aspect, the invention concerns an isolated PR01486 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 33 through 205 of Figure 162 (SEQ ID N0:287).
In yet another aspect, the invention concerns an isolated PRO 1486 polypeptide, comprising the sequence of amino acid residues 33 to about 205, inclusive of Figure 162 (SEQ ID
N0:287), or a fragment thereof sufficient to provide a binding site for an anti-PR01486 antibody. Preferably, the PR01486 fragment retains a qualitative biological activity of a native PROI486 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01486 polypeptide having the sequence of amino acid residues from about 33 to about 205, inclusive of Figure 162 (SEQ ID N0:287), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01486 polypepiide. In a particular embodiment, the agonist or antagonist is an anti=PR01486 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01486 polypeptide, by contacting the native PR01486 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1486 polypeptide, or an agonist or antagonist as hereinabove defined, in combination 'with a pharmaceutically acceptable Garner.
82. PR01433 A cDNA clone (DNA71184-1634) has been identified that encodes a novel transmembrane poiypeptide, designated in the present application as "PR01433".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01433 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1433 polypeptide having the sequence of amino acid residues from about 1 to about 388, inclusive of Figure 164 (SEQ ID N0:292), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucieic acid molecule encoding a PR01433 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 185 and about 1348, inclusive, of Figure 163 (SEQ ID N0:291). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203266 (DNA71184-1634) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203266 (DNA7I184-1634).
in still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 388, in<:lusive of Figure 164 (SEQ iD N0:292), or (b} the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 250 nucleotides and produced by hybridizing a test DNA molecule nulder stringent conditions with (a) a DNA
molecule encoding a PR01433 polypeptide having the sequence of amino acid residues from 1 to about 388, inclusive of Figure 164 (SEQ ID N0:292), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a FR01433 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about a~~ino acid position 76 to about amino acid position 97 in the PR01433 amino acid sequence (Figure 164, SEQ ID N0:292).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 388, inclusive of figure 164 (SEQ
ID N0:292), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01433 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 163 (SEQ ID NC1:29I).
In another embodiment, the invention provides isolated: PROI433 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01433 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 388 of Figure I64 (SEQ
ID N0:292).
In another aspect, the invention concerns. an isolated PROI433 polypeptide, comprising an amino acid IO sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I to about 388, inclusive of Figure 164 {SEQ
ID N0:292).
In a further aspect, the invention concerns an isolated PRIJ 1433 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at Least about 8S %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 388, inclusive of Figure 164 (SEQ ID N0:292).
In yet another aspect, the invention concerns an isolated PRO 1433 polypeptide, comprising the sequence of amino acid residues 1 to about 388, inclusive of Figure 164 (SEQ ID
N0:292), or a fragment thereof sufficient to provide a binding site for an anti-PR01433 antibody. Preferably, the PR01433 fragment retains a qualitative biological activity of a native PR01433 polypeptide.
In a still farther aspect, the invention provides a poIypep~tide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule e~acoding a PR01433 polypeptide having the sequence of amino acid residues from about I to about 388, inclusive of Figure 164 (SEQ ID N0:292), or (b) the complement of the DNA molecule of (a), and if the test DNA :molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to {a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01433 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROI433 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01433 polypeptide by contacting the native PR01433 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1433 polypeptide, 3S or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
WO 00/12708 PCT/U599/2011 t 83. PR01490 A cDNA clone (DNA71213-1659) has been identified, having homology to nucleic acid encoding a i-acyl-sn-glycerol-3-phosphate acyltransferase protein that encodes a novel polypeptide, designated in the present application as "PR01490".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01490 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1490 polypeptide having the sequence of amino acid residues from about l .or about 26 to about 368, inclusive of Figure 166 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01490 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 272 or about 347 and about 1375, inclusive, of Figure 165 (SEQ ID N0:296).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a} a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203401 (DNA71213-1659) or (b} the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203401 (DNA7I213-1659).
In still a further aspect, the invention concerns an isolatedl nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at Least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to aibout 368, inclusive of Figure 166 (SEQ ID
N0:297), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 285 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a 1?R01490 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID N0:297), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, ;prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01490 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 2S in the sequence of Figure 166 (SEQ
ID N0:297). The transmembrane domains have been tentatively identified as extending from about amino acid position 307 to about amino acid position 323 and from about amino acid position 33S to about amino acid position 3S2 in the PR01490 amino acid sequence (Figure 166, SEQ ID N0:297).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a} DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 8S% positives, more preferably at least about 90 % positives, most preferably at least about 9S %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID N0:297); or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1490 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 16S (SEQ ID N0:296).
In another embodiment, the invention provides isolated PR01490 polypeptide encoded by any of the IS isolated nucleic acid sequences hereinabove identified.
In a speck aspect; the invention provides isolated native sequence PR01490 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 368 of Figure 166 (SEQ ID N0:297).
in another aspect, the invention concerns an isolated PRO1490 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity; preferably at least about SS% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID N0:297).
In a further aspect, the invention concerns an isolated PRC> 1490 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90% positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID
N0:297).
In yet another aspect, the invention concerns an isolated PR01490 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID N0:297), or a fragment thereof sufficient to provide a binding site for an anti-PR01490 atuibody.
Preferably, the PRO1490 fragment retains a qualitative biological activity of a native PROI490 polypeptide.
In a still further aspect, the invention provides a polypep~dde produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01490 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 368, inclusive of Figure 166 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 8S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 9S% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) wo oonz~as PCT/US99/2o111 recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonzsts and antagonists of a native PR01490 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01490 antibody.
In a further embodiment, the invention concerns a metlhod of identifying agonists or antagonists of a native PR01490 polypeptide by contacting the native PR01490 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01490 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
84. PR01482 A cDNA clone (DNA71234-1651) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PROi482".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01482 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01482 polypeptide having the sequence of amino acid residues from about I or about 29 to about 143, inclusive of Figure 168 (SEQ ID
N0:302), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01482 polypeptide comprising DNA hybridizing to the complement of tree nucleic acid between about nucleotides 33 or about 117 and about 461, inclusive, of Figure 167 (SEQ ID N0: 301).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8530 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95Ro sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203402 {DNA71234-1651) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment; the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein eDNA in ATCC Deposit No. 203402 (DNA71234-165I).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID
N0:302), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 260 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with {a) a DNA
molecule encoding a PROI482 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 143, inclusive of Figure 168 {SEQ ID N0:302), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01482 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 168 (SEQ
ID N0:302).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302), or (b) the complement of the DNA of {a).
Another embodiment is directed to fragments of a PR01482 poiypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 167 (SEQ ID N0:301).
In another embodiment, the invention provides isolated 1PR01482 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01482 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 143 of Figure 168 (SEQ ID N0:302}.
In another aspect, the invention concerns an isolated PR01482 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID N0:302).
In a further aspect, the invention concerns an isolated PRO 1482 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 143, inclusive of Figure 168 (S1EQ ID
N0:302}.
In yet another aspect, the invention concerns an isolated PRO 1482 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 143, inclusive of Fi,gttre 168 (SEQ ID N0:302}, or a fragment thereof sufficient to provide a binding site for an anti-PR01482 antibody.
Preferably, the PR01482 fragment retains a qualitative biological activity of a native PR01482 polypE;ptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01482 polypeptide having the WO OO/I2708 PCT'/US99120111 sequence of amino acid residues from about 1 or about 29 to about 143, inclusive of Figure 168 (SEQ ID
N0:302), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 8S% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns al;onists and antagonists of a native PR01482 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01482 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native-PR01482 polypeptide by contacting the native PROI482 polypeptide with a candidate molecule and I0 monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a cornposition comprising a PR01482 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
85. PROI446 A cDNA clone (DNA71277-1636) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01446."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01446 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA lhaving at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1446 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 109, inclusive of Figure 170 (SEQ ID N0:304), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01446 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 197 and about 478, inclusive, of Figure 169 (SEQ ID N0:303). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least 34 about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203285 (DNA71277-1636), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203285 (DNA71277-1636).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 16 t:o about 109, inclusive of Figure 170 (SEQ ID
NO:304), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01446 polypeptide having the sequence of amino acid residues from about 16 to about 109, inclusive of Figure 170 (SEQ
ID N0:304), or (b) the complement of the DNA molecule of (a), and; if the DNA molecoIe has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or {b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at Least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 16 to about 109, inclusive of Figure 170 (SEQ
ID N0:304), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01446 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, nnore preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to abouit 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01446 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01446 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 through 109 of Figure 170 (SEQ ID
N0:304).
In another aspect, the invention concerns an isolated PRG 1446 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at Least about 95 % sequence identity to the sequence of amino acid residues 16 to about 109, inclusive of Figure 170 (SEQ
ID N0:304).
in a further aspect, the invention concerns an isolated PRCI1446 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at Least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 through 109 of Figure 170 (SEQ ID N0:304).
In yet another aspect, the invention concerns an isolated PRO1446 polypeptide, comprising the sequence of amino acid residues 16 to about 109, inclusive of Figure 170 (SEQ ID
N0:304), or a fragment thereof sufficient to provide a binding site for an anti-PR01446 antibody. Preferably, the PR01446 fragment retains a qualitative biological activity of a native PR01446 polypepdde.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1446 polypeptide having the sequence of amino acid residues from about 16 to about 109, inclusive of Figure 170 (SEQ ID N0:304), or (b) the complement of the DNA molecule of (a), and if the test DNA. molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01446 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01446 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01446 polypeptide, by contacting the native PR0144Ei polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1446 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
86. PRO1558 A cDNA clone (DNA71282-1668) has been identified, having homology to nucleic acid encoding methyltransferase enzymes that encodes a novel polypeptide, designated in the present application as "PR01558".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01558 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA rnolec;ule encoding a PR01558 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID
N0:306), or (b} the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1558 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 84 or about 159 and about 869, inclusive, of Figure 171 (SEQ ID N0:305).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%i sequence identity to (a) a DNA molecule encoding the same mature palypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203312 (DNA71282-1668) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203312 (DNA71282-1668).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence .
identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence wo oonz7o8 PCTIUS99/2o111 identity to the sequence of amino acid residues I or about 26 to about 262, inclusive of Figure 172 (SEQ ID
N0:306}, or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01558 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereabiy at least about an 8S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides .an isolated nucleic acid molecule comprising DNA encoding a PROI558 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 25 in the sequence of Figure I72 (SEQ
ID N0:306). The transmembrane domains have been tentatively identified as extending from about amino acid position 8 to about amino acid position 30 and from about amino acid position 109 to almut amino acid position 130 in the PR01558 amino acid sequence (Figure I72, SEQ ID N0:306).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80%~positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least atbut 95%
positives when compared with the amino acid sequence of residues I or about 26 tv about 262, inclusive of Figure 172 (SEQ ID N0:306), or (b) the complement of the DNA of (a}.
Another embodiment is directed to fragments of a PROi558 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure I71 (SEQ ID N0:305).
In another embodiment, the invention provides isolated PFC01558 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01558 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 262 of Figure I72 (SEQ ID N0:306 In another aspect, the invention concerns an isolated PRO1_i58 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably ar. least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amine acid residues I or about 26 to about 262, inclusive of Figure 17(SEQ ID N0:306 In a further aspect, the invention concerns an isolated PR01558 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 262, inclusive of Figure 17(SEQ ID N0:306 In yet another aspect, the invention concerns an isolated PR01558 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 262, inclusive of Fiigure 172 (SEQ ID N0:306), or a fragment thereof sufficient to provide a binding site for an anti-PR01558 antibody.
Preferably, the PR01558 fragment retains a qualitative biological activity of a native PR01558 poiypeptide;
In a still further aspect, the invention provides a poiypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01558 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 262, inclusive of Figure 172 (SEQ ID
N0:306), or (b) the complement of the DNA molecule of (a), and. if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01558 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01558 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1S58 polypeptide by contacting the native PR01558 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1558 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
87. PR01604 A cDNA clone {DNA7I286-1687) has been identified that encodes a novel polypeptide having homology to hepatoma-derived growth factor (HDGF) designated in the presc;nt application as "PRO1b04".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01604 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to {a) a DNA molecule encoding a PR01604 polypeptide having the sequence of amino acid residues from 1 or about 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nu.cieic acid molecule encoding a PRO1604 polypeptide comprising DNA hybridizing to the complement of the rAUCleic acid between about residues 104 and about 2077, inclusive, of Figure 173 (SEQ ID N0:307). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at .least about 8S %
sequence identity, more preferably at Least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203357 (DNA71286-1687), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203357 (DNA71286-1687).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at Least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 14 to about 671, inclusive of Figure 174 (SEQ ID
N0:308), or the complement of the DNA of (a)..
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01604 polypeptide having the sequence of amino acid residues from about 14 to about 671, inclusive of Figure I74 (SEQ
ID N0:308), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, Z5 preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferahly at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI604 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 13 in the sequence of Figure 174 (SEQ ID
N0:308).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a poiypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 14 to about 671, inclusive of Figure 174 (SEQ
ID N0:308), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR016!)4 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01604 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01604 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 14 to 67I of Figure 174 (SEQ ID N0:308).
In another aspect, the invention concerns an isolated PR01604 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at Least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 14 to about 67I, inclusive of Fiyre 174 (SEQ
ID N0:308).
In a further aspect, the invention concerns an isolated PRO1604 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the aarino acid sequence of residues 14 to 671 of Figure i74 (SEQ ID N0:308).
In yet another aspect, the invention concerns an isolated PB:01604 polypeptide, comprising the sequence of amino acid residues 14 to about 671, inclusive of Figure 17f. (SEQ iD
N0:308), or a fragment thereof sufficient to provide a binding site for an anti-PR01604 antibody. Preferably, the PROI604 fragment retains a qualitative biological activity of a native PR01604 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01604 polypeptide having the sequence of amino acid residues from about 14 to about 671, inclusive of Figure 174 (SEQ ID N0:308), or (b}
the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) ar (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii} recovering the polypepcide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01604 polypeptide. In a particular embodiruent, the agonist or antagonist is an anti-PR01604 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01604 polypeptide, by contacting the native PR01604 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment; the invention concerns a composition comprising a PR01604 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
88. PROI491 A cDNA clone (DNA71883-1660) has been identified, having hornoIogy to nucleic acid encoding a collapsin protein, that encodes a novel polypeptide, designated in tlhe present application as "PROI491 ".
In one embodiment; the invention provides an isolated nucleeic acid molecule comprising DNA encoding a PR01491 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1491 poiypeptide having the sequence of amino acid residues from about 1 or about 37 to about 777, inclusive of Figure 176 (SEQ iD
N0:310), or (b) the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01491 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 107 or about 2I5 and about 2437, inclusive, of Figure 175 (SEQ ID N0:309).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203475 (DNA71883-1660) or (b} the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit Na. 203475 (DNA71883-1660).
In still a furthex aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, rnost preferably at least about 95 % sequence IO identity to the sequence of amino acid residues 1 or about 37 to .about 777, inclusive of Figure 176 (SEQ ID
N0:310), or (b) the complement of the DNA of (a).
. In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 1,670 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01491 polypeptide having the sequence o~f amino acid residues from 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01491 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 36 in the sequence of Figure 176 (SEQ
ID N0:310).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:3I0), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01491 poiypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from. about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 175 (SEQ ID N0:309).
In another embodiraent, the invention provides isolated Plft01491 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native; sequence PRO1491 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 37 to about 777 of Figure WO 00/12708 PCTlUS99I20111 176 (SEQ ID N0:310).
In another aspect, the invention concerns an isolated PR01491 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:3I0).
In a further aspect, the invention concerns an isolated PRO 1491 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at feast about 95 % positives when compared with the amino acid sequence of residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID
N0:310).
In yet another aspect, the invention concerns an isolated PR.O 1491 polypeptide, comprising the sequence of amino acid residues 1 or about 37 to about 777, inclusive of Figure 176 (SEQ ID N0:310), or a fragment thereof sufficient to provide a binding site for an anti-PR01491 antibody.
Preferably, the PR01491 fragment retains a qualitative biological activity of a native PR01491 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01491 polypeptide having the sequence of amino acid residues from about 1 or about 37 to albout 777, inclusive of Figure 176 (SEQ ID
N0:310), or (b) the complement of the DNA raolecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01491 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01491 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01491 polypeptide by contacting the native PR01491 ;polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1491 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
89. PR01431 A cDNA clone (DNA73401-1633) has been identified having a domain with homology to SH3 that encodes a novel polypeptide, which has been designated in the present application as "PR01431".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01431 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, 3S preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1431 polypeptide having the sequence of amino acid residues from about 1 to about 370, inclusive of Figure 178 {SEQ ID N0:315) or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01431 poiypeptide comprising DNA hybridizing to the complement of the nucleic acid between residues l to about 1335 and about 1560 to about 3934, inclusive, of Figure I77 (SEQ ID N0:314).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns (a) an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % , sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203273 (DNA73401-1633) or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA iw ATCC
Deposit No. 203273 (DNA73401-1633).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having aC least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 370, inclusive, of Figure 178 (SEQ ID
N0:315), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 15 nucleotides that is produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01431 polypeptide having the sequence of amino acid residues from about 1 to about 370, inclusive, of Figure 178 (SEQ ID N0:315), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 370; inclusive, of Figure 178 (SEQ
ID N0:315), inclusive, of Figure 178 (SEQ ID N0:315).
In another embodiment, the invention provides isolated PFt01431 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specif c aspect, the invention provides isolated native sequence PRO 1431 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues :l to 370, inclusive, of Figure 178 (SEQ ID
N0:315).
In another aspect, the invention concerns an isolated PR01431 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 370, inclusive, of Figure 178 (SEQ
ID N0:315).
In a further aspect, the invention concerns an isolated PRO 1431 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 9S % positives when compared with the amino acid sequence of residues 1 to 370 of Figure 178 (SEQ ID N0:3I5).
In yet another aspect, the invention concerns an isolated PR01431 or PR01432 polypepdde, comprising the sequence of amino acid residues 1 to about 370, inclusive, or Figure 178 (SEQ ID N0:315}, inclusive, of Figure 178 (SEQ ID N0:315), or a fragment thereof sufficient to provide a binding site for an anti-PR01431 antibody. Preferably, the PROI431 fragment retains a qualitative biological activity of a native PROI431 polypeptide.
In a still further aspect, the invention provides a polype~ptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01431 polypeptide having the sequence of amino acid residues from about 1 to about 370, unclusive, of Figure 178 (SEQ ID N0:315), inclusive, of Figure 178 (SEQ ID N0:315), or (b) the complement of the DNA
molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most prei:erably at least about a 95% sequence identity to (a) or (b); (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypepdde from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01431 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROI431 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01431 polypeptide, by contacting the native PR01431 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01431 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
90. PR01563 A cDNA clone (DNA73492-1671) has been identified, having homology to nucleic acid encoding ADAMTS-1 that encodes a novel polypeptide, designated in the present application as "PR01563".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01563 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PRO15b3 polypeptide having the sequence of amino acid residues from about I or about 49 to about 837, inclusive of Figure 180 (SEQ ID
N0:3I7), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01563 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 419 or about 563 and about 2929, inclusive, of Figures I79A-B (SEQ ID N0:316}.
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect; the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9590 sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203324 (DNA73492-167/) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203324 (DNA73492-1671).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80%. sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID
N0:317), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01563 polypeptide having the sequence oi~ amino acid residues from 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:3I7), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at /east about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01563 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 48 in the sequence of Figure 180 (SEQ
ID N0:317).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:3I7), or (b) the complement of the DNA of (a).
34 Another embodiment is directed to fragments of a PR0156 3 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and maybe derived from the nucleotide sequence shown in Figures 179A-B (SEQ ID rf0:316).
In another embodiment, the invention provides isolated PF~,01563 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01563 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 49 to about 837 of Figure 180 (SEQ ID N0:317).
In another aspect, the invention concerns an isolated PR0~1563 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure 180 (SEQ ID N0:3I7).
In a further aspect, the invention concerns an isolated PR0~1563 polypeptide;
comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues i or about 49 to about 837, inclusive of Figure 180 (S:EQ ID
N0:317).
In yet another aspect, the invention concerns an isolated PRO 1563 polypeptide, comprising the sequence of amino acid residues 1 or about 49 to about 837, inclusive of Figure i80 (SEQ ID NO:317), or a fragment thereof sufficient to provide a binding site for an anti-PR01563 antibody.
Preferably, the PR01563 fragment retains a qualitative biological activity of a native PR01563 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule er,~coding a PR01563 poiypeptide having the sequence of amino acid residues from about 1 or about 49 to about 837, inclusive, of Figure 180 (SEQ ID
N0:317), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable ifor expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet anoitzer embodiment, the invention concerns agonists and antagonists of a native PR01563 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROI563 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01563 polypeptide by contacting the native PR01563 p~olypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1563 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
91. PR01565 A cDNA clone (DNA73727-1673) has been identified, having homology to nucleic acid encoding a chondromodulin protein that encodes a novel polypeptide, designated in the present application as "PR01565".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01565 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, snore preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01565 polypeptide having the sequence of amino acid residues from about 1 or about 41 to .about 317, inclusive of Figure 182 (SEQ ID
N0:322), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01565 polypeptide comprising DNA hybridizing to the complement of tine nucleic acid between about nucleotides 59 or about 179 and about 1009, inclusive, of Figure 181 (SEQ ID N0:321).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8590 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 959'o sequence identity to (a) a DNA molecule encoding the same mature poiypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203459 (DNA73727-1673) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203459 (DNA73727-1673).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence IS identity, more greferabIy at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID
N0:322), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 410 nucleotides and produced by hybridizing a test DNA molecule vender stringent conditions with (a) a DNA
molecule encoding a PR01565 polypeptide having the sequence of amino acid residues from 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID N0:322), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01565 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively ide~at~ed as extending from about amino acid position 1 to about amino acid position 40 in the sequence of Figure 182 (SEQ
ID N0:322). The transmembrane domain has been tentatively identified as extending from about amino acid position 25 to about amino acid position 47 in the PR01565 amino acid sequence (Figure 182, SE(> ID N0:322).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least abt~ut 95%
positives when compared with the amino acid sequence of residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID N0:322), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01565 poiypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are. from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, tx~ore preferably from about 20 to about 50 nucleotides in: length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 181 (SEQ ID N0::321).
In another embodiment, the invention provides isolated PR01565 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01565 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 41 to abort 3I7 of Figure 182 (SEQ ID N0:322).
In another aspect, the invention concerns an isolated PR01565 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, mare preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 41 to about 317, inclusive of Figure 182 (SEQ ID N0:322).
In a further aspect, the invention concerns an isolated PR01565 polypeptide;
comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 41 to about.3l7, inclusive of Figure 182 (SEQ ID
N0:322).
In yet another aspect, the invention concerns an isolated PR01565 polypeptide, comprising the sequence of amino acid residues 1 or about 41 to about 31?, inclusive of Figure 182 (SEQ ID N0:322), or a fragment thereof sufficient to provide a binding site for an anti-PR01565 antibody.
Preferably, the PR01565 fragment retains a qualitative biological activity of a native PROI565 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01565 polypeptide having the sequence of amino acid residues from about 1 or about 41 to akwut 317, inclusive of Figure 182 (SEQ ID
N0:322), or (b) the complement of the DNA molecule of {a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to {a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable :for expression of the poiypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agottists and antagonists of a native PR01565 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01565 antibody.
In a further embodiment, the invention concerns a method of identifying aganists or antagonists of a native PR01565 polypeptide by contacting the native PRO1565 holypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01565 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
92. PR01571 A cDNA clone (DNA73730-1679) has been identified, l:~aving homology to nucleic acid encoding the clostridium perfringens enterotoxin receptor (CPE-R) that encodes a novel polypeptide, designated in the present application as "PRO1S71".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1S71 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8S % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a FRO1S71 polypeptide having the sequence of amino acid residues from about 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID
N0:324), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1S71 polypeptide comprising DNA hybridizing co the complement of the nucleic acid between about nucleotides 90 or about 1S3 and about 806, inclusive, of Figure I83 (SEQ ID N0:323).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203320 (DNA73730-1679) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203320 (DNA73730-1679).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a pvlypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, nnost preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID
N0:324), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 9I0 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PRO1S71 polypeptide having the sequence of amino acid residues from 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID N0:324), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity" prefereably at least about an 8S % sequence identity, more preferably at least about a 90% sequence identity, rr~ost preferably at least about a 9S% sequence identity to {a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding 3S a PRO1S71 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary.to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid WO OOIIZ70$ PCT/US99/Z0111 position 1 to about amino acid position 21 in the sequence of Figure 184 (SEQ
ID N0:324). The transmembrane domains have been tentatively identified as eztending from about amino acid position 82 to about amino acid position 103, from about amino acid position 115 to about amino acid position 141 and from about amino acid position 160 to about amino acid position 182 in the PR01571 .amino acid sequence (Figure 184, SEQ ID
N0:324).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polygeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID N0:324), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR015T I polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure i83 (SEQ ID N0:323).
In another erabodiment; the invention provides isolated PR0157i polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01571 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 22 to about 239 of Figure 184 (SEQ ID N0:324).
In another aspect, the invention concerns an isolated PR01.57I polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably ,at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 22 to about 239, inclusive of Figure I84 (SEQ ID N0:324).
In a further aspect, the invention concerns an, isolated PRO 1:571 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 22 to about 239, inclusive of Figure 184 (S~;Q ID
N0:324).
In yet another aspect, the invention concerns an isolated PROI571 polypeptide, comprising the sequence of amino acid residues 1 or about 22 to about 239, inclusive of Figure 184 (SEQ ID N0:324), or a fragment thereof sufficient to provide a binding site for an anti-PR01571 antibody.
Preferably, the PR01571 fragment retains a qualitative biological activity of a native PR01571 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i} hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0157I
polypeptide having the sequence of amino acid residues from about 1 or about 22 to ab~~ut 239, inclusive of Figure 184 (SEQ ID
N0:324), or {b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least almut a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable far expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01571 polypepiide. In a particular embodiment, the agonist or antagoniist is an anti-PR01571 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01571 polypeptide by contacting the native PR01571 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a cormposition comprising a PR01571 polypeptide, or an agoztist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
IO 93. PR01572 A cDNA clone (DNA73734-1680) has been identified that encodes a novel polypeptide having sequence identity with CPE-R and designated in the present application as "PRO15?2."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1S72 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01572 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 261, inclusive of Figure 186 (SEQ ID N0:326), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns as isolated nucleic acid molecule encoding a PR01572 polypeptide comprising DNA hybridizing to the complement of the: nucleic acid between about residues 159 and about 872, inclusive, of Figure 185 (SEQ ID N0:325). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203363 (DNA73734-1680), or (b) the complement of the DNA molecule of {a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poFypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203363 (DNA73734-1680).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising {a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 (SEQ ID
N0:326), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01572 polypeptide having the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 {SEQ
ID N0:326), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at Ieast about a 95 % sequence identity to (a) or {b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01572 poIypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 186 (SEQ ID
NO:326). The transmembrane domains have been tentatively identified as approximately at about 8 i-100, 121-14i and 173-194 in the PR01572 amino acid sequence (Figure 186, SEQ ID N0:326).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 24 to about 261, inclusive of Figure 186 (SEQ
ID N0:326), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01572 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about SO nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 24 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1?R01572 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01572 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 261 of Figure 186 (SEQ ID
N0:326).
In another aspect, the invention concerns an isolated PRO 1572 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 261, inclusive of Figure 186 {SEQ
ID N0:326).
In a further aspect, the invention concerns an isolated PRO1572 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 through 261 of Figure 186 (SEQ ID N0:326).
In yet another aspect, the invention concerns an isolated PR01572 polypeptide, comprising the sequence of amino acid residues 24 to about 261, inclusive of Figure 186 (SEQ ID
N0:326), or a fragment thereof sufficient to provide a binding site for an anti-PR01572 antibody. Preferably, the PR01572 fragment retains a qualitative biological activity of a native PR01572 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0157Z
polypeptide having the sequence of amino acid residues from about 24 to about 261, inclusive of Figure 186 (SEQ ID N0:326), or (b) the camplement of the DNA molecule of (a), and if the test DNA, molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PRO1572 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1572 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01572 polypeptide, by contacting the native PR01572 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a conaposition comprising a PRO 1572 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
94. PR01573 A cDNA clone (DNA73735-1681) has been identified that encodes a novel polypeptide having sequence identity with CPE-R and designated in the present application as "'PR01573".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01573 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA lhaving at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01573 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 22:i, inclusive of Figure 188 (SEQ ID N0:328), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01573 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 148 and about 771, inclusive, of Figure 187 (SEQ ID N0:327). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nuc;leic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85%~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203356 (DNA73735-1681), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide enccuied by the human protein cDNA in ATCC
Deposit No. 203356 (DNA73735-1681).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
WO 00/12708 PCTlUS99I20111 encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence ideatity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 225, inclusive of Figtue 188 (SEQ ID
N0:328), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P:ROI573 polypeptide having the sequence of amino acid residues from about 18 to about 225, inclusive of Figure 188 (SEQ
ID N0:328), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule; has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity,.more preferably at least about a 90% sequence identity, most IO preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01573 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding .
nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 1.88 (SEQ ID
N0:328). The transmembrane domains have been tentatively identified as at approximately 82-101, 118-145 and 164-188 in the PR01573 amino acid sequence (Figure 188, SEQ ID N0:328).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 18 to about 225, inclusive of Figure 188 (SEQ
ID N0:328), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR015'13 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length; and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated fR01573 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01573 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 through 225 of Figure 188 (SEQ ID
N0:328).
In another aspect, the invention concerns an isolated PRO 1573 polygeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 9096 sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 18 to about 225, inclusive of Figure 188 (SEQ
ID N0:328).
In a further aspect, the invention concerns an isolated PRO 1573 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 through 225 of Figure 188 (SEQ ID N0:328).
In yet another aspect, the invention concerns an isolated PR01573 polypeptide, comprising the sequence of amino acid residues 18 to about 225, inclusive of Figure I88 (SEQ iD
N0:328), or a fragment thereof sufficient to provide a binding site for an anti-PR01573 antibody. Preferably, the PRO1573 fragment retains a qualitative biological activity of a native PR01573 polypeptide.
In a still further aspect, the invention provides a polypE;ptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01573 polypeptide having the sequence of amino acid residues from about 18 to about 225, inclusive of Figure 188 (SEQ ID N0:328), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity; more preferably at least about a 90% sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poiypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01573 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PROiS73 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01573 polypeptide, by contacting the native PRO157.3 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1573 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
95. PR 1488 A cDNA clone (DNA73736-1657) has been identified that encodes a novel polypeptide having homology to Clostridium perfringens enterotoxin receptor (CPE-R), designated in the present application as "PR01488".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01488 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01488 polypeptide having the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01488 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 6 and about 665, inclusive, of Figure 189 (SEQ ID N0:329). PrefE;rably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA haviung at least about 80% sequence identity, preferably at least about 85!% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203466 (DNA73736-1657), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203466 (DNA73736-1657).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, rmost preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID
N0:330), or the complement of the DNA of (a).' .
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01488 polypeptide having the sequence of amino acid residues from about 1 to about 220, inclusive of Figure 190 (SEQ ID
N0:330), or (b) the complement of the DNA molecule of {a), and, if the DNA molecule has at least about an 80 % sequence identity, I S preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01488 polypeptide, with or without the initiating methionine, and its soluble variants (i.e. Lransmembrajne domains deleted or inactivated), or is complementary to such encoding nucleic acid molecule. Transmembrane domains has been tentatively identified as being located at about amino acid positions 8-30, 82-102, 121-140, and 166-186 in the PR01488 amino acid sequence (Figure 190, SIEQ ID N0:330}.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at Least about 95%
positives when compared with the amino acid sequence of residues 1 to. about 220, inclusive of I~igure 190 (SEQ
ID N0:330), or {b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01488 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01488 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1488 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 220 of Figure 190 (SEQ ID N0:330).
In another aspect, the invention concerns an isolated PR01488 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably au least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably as least about 95% sequence identity to the sequence of amino acid residues 1 to about 220, inclusive of Figure 190 (SEQ
ID N0:330).
In a further aspect, the invention concerns an isolated PR01488 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I to 220 of Figure 190 (SEQ ID N0:330).
In yet another aspect, the invention concerns an isolated P1f~01488 polypeptide, comprising the sequence of amino acid residues I to about 220, inclusive of Figure 190 (SEQ ID
N0:330), or a fragment thereof sufficient to provide a binding site for an anti-PROI488 anribody. Preferably, the PR01488 fragment retains a qualitative biological activity of a native PR01488 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01488 polypeptide having the sequence of amino acid residues from about I to about. 220, inclusive of Figure 190 (SEQ ID N0:330), or (b) the complement of the DNA molecule of (a), and if the test DNA. molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a} or (b), {ii) culturing a host cell comprising I5 the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01488 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01488 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01488 polypeptide, by contacting the native PR0148.8 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01488 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
96. PR01489 A cDNA clone (DNA73737-1658) has been identified, lhaving homology to nucleic acid encoding the clostridium perfringens enterotoxin receptor (CPE-R) that encodes a novel polypeptide, designated in the present application as "PR01489".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01489 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA. having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01489 polypeptide having the sequence of amino acid residues from about 1 to about 173, inclusive of Figure 192 (SEQ ID N0:332), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01489 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 264 and about 782, inclusive, of Figure 191 (SEQ ID N0:331). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invenrion concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity; more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human p3rotein cDNA in ATCC Deposit No. 203412 (DNA73737-1658) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypehtide encoded by the human protein cDNA in ATCC Deposit No. 203412 (DNA73737-1658).
In still a further aspect; the invention concerns an isoiate;d nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 173, inclusive of Figure 192 (SEQ ID N0:332), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolatc;d nucleic acid molecule having at least 25 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01489 poIypeptide having the sequence of amino acid residues front 1 to about 173,, inclusive of Figure 192 (SEQ ID N0:332), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01489 polypeptide, with or without the initiating methionine;, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from abom amino acid position 31 to about amino acid position 51, from about amino acid position 71 to about amino acid position 90 and from about amino acid position 112 to about amino acid position 133 in the PR01489 amino acid sequence (Figure 192, SEQ ID
N0:332).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least. about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 173, inclusive of Figure 192 (SEQ
ID N0:332); or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01489 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 191 (SEQ ID NC):331).
WO OOII2?08 PCTIUS99/20111 In another embodiment, the invention provides isolated PR01489 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01489 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 173 of Figure 192 (SEQ
ID N0:332).
In another aspect, the invention concerns an isolated PR01489 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 173, inclusive of Figure 192 (SEQ
ID N0:332).
In a further aspect, the invention concerns an isolated PR~01489 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about I73, inclusive of Figure 192 {SEQ ID N0~:332).
In yet another aspect, the invention concerns an isolated PRO 1489 polypeptide, comprising the sequence of amino acid residues 1 to about 173, inclusive of Figure 192 (SEQ ID
N0:332), or a fragment thereof sufficient to provide a binding site for an anti-PR01489 antibody. Preferably, the PR01489 fragment retains a qualitative biological activity of a native PR01489 polypeptide;.
In a still further aspect, the invention provides a polype;ptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01489 polypeptide having the sequence of amino acid residues from about 1 to about 173, inclusive of Figure 192 (SEQ ID N0:332), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide frora the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01489 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01489 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01489 polypeptide by contacting the native PR01489 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01489 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable earner.
97. PROi474 A cDNA clone {DNA73739-1645) has been identified that encodes a novel polypeptide having sequence identity with ovomucoid and designated in the present application as "PR01474."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR014?4 polypeptide.
WO 00112708 PCTlUS99IZOtII
In one aspect, the isolated nucleic acid comprises DNA, having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity; most preferably at least about 95 % sequence idemity to (a) a DNA molecule encoding a PR01474 polypeptide having the sequence of amino acid residues from 1 or about 20 to about fi5, inclusive of Figure 194 (SEQ iD N0:334), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01474 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 102 and about 299, inclusive, of Figure 193 (SEQ ID N0:333). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least.about 80% sequence identity, preferably at least about 8:i% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9~ % sequence ideatity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203270 (DNA73739-1645), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203270 (DNA73739-1645).
In a still further aspect, the invention concerns an isolarxd nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 85, inclusive of Figure 194 (SEQ ID
N0:334), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PROI474 polypeptide having the sequence of amino acid residues from about 20 to about 85, inclusive o:f Figure 194 (SEQ
ID N0:334), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, F~referably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 85, inclusive of Figure 194 (SEQ
ID N0:334), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01474 polypeptide coding sequence that may ftnd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolatedl PR01474 polypeptide encoded by any of the PCTlUS99120111 isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1474 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 85 of Figure 194 (SEQ ID
N0:334).
In another aspect, the invention concerns an isolated PR01474 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 85, inclusive of Figure 194 (SEQ
ID N0:334).
In a farther aspect, the invention concerns an isolated PR.01474 polypeptide, comprising an amino acid sequence scoring at least about 80 k positives, preferably at least. about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 85 of Figure 194 (SEQ ID N0:334).
In yet another aspect, the invention concerns an isolated f RO I474 polypeptide, comprising the sequence of amino acid residues 20 to about 85, inclusive of Figure 1!~4 (SEQ ID
N0:334), or a fragment thereof sufficient to provide a binding site for an anti-PR01474 antibody. Preferably, the PR01474 fragment retains a qualitative biological activity of a native PR01474 polypeptide.
In a still further aspect, the invention provides a polyF~eptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA moleculc; encoding a PR01474 polypegtide having the sequence of amino acid residues from about 20 to about 85, inclusive of Figure 194 (SEQ ID N0:334), or (b) the complement of the DNA molecule of (a), and if the test DrfA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01474 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01474 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01474 polypeptide, by contacting the native PR01474 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide,.
In a still further embodiment, the invention concerns a composition comprising a PR01474 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
gg, PRO1508 A cDNA clone (DNA73742-1662) has been identified that encodes a novel secreted polypeptide and designated in the present application as "PR01508."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROi508 polypeptide.
In one aspect, the isolated nucleic acid comprises T>NA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01508 polypeptide having the sequence of amino acid residues from 1 or about 31 to about 148, inclusive of Figure 196 (SEQ ID N0:336), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01508 polypeptide comprising DNA hybridizing to the complement of thc; nucleic acid between about residues 160 and about 513, inclusive, of Figure 195 (SEQ ID N0:335). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least IO about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203316 (DNA73742-1662), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203316 (DNA73742-1662).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, :most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 31 to about 148, inclusive of Figure 196 (SEQ ID
N0:336), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a 1PR01508 polype:ptide having the sequence of amino acid residues from atmut 31 to about 148, inclusive of Figure 196 (SEQ
ID N0:336), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01508 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 30 in the sequence of Figure 196 (SEQ
ID N0:336).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives; more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 31 to about 148, inclusive oiP Figure i96 (SEQ
ID N0:336), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01:508 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01508 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1508 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 31 to 148 of Figure 196 (SEQ ID N0:336).
In another aspect, the invention concerns an isolated PRO1508 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 31 to about 148, inclusive of Figure 196 (SEQ
ID N0:336).
In a further aspect, the invention concerns an isolated PRO 1508 poiypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 31 to 148 of Figure 196 (SEQ iD N0:336).
In yet another aspect, the invention concerns an isolated PRO 1508 polypeptide, comprising the sequence of amino acid residues 31 to about 148, inclusive of Figure 196 (SEQ ID
N0:336), or a fragment thereof sufficient to provide a binding site for an anti-PR01508 antibody. Preferably, the PR01508 fragment retains a qualitative biological activity of a native PR01508 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01508 polypeptide having the sequence of amino acid residues from about 31 to about 148, inclusive of Figure 196 (SEQ ID N0:336), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
99. P. RO1S55 A cDNA clone (DNA73744-1665) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01555".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01555 polypepdde.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity;
preferably at least about 85% sequence identity, more preferalbly at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01555 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 246, inclusive of Figure 198 (SEQ ID N0:338), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01555 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 83 and about 827, inclusive, of Figure 197 (SEQ, ID N0:337). Preferably, hybridization .occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203322 (DNA73744-1665), or (b) the complement of the DNA molecule; of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203322 (DNA73744-1665).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a palypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity; more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 246, inclusive of Figure 198 (SEQ ID
N0:338), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having 'at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01555 polypeptide having the sequence of amino acid residues from about 32 to about 246, inclusive: of Figure 198 (SEQ
ID N0:338), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding . .
a PR01555 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains deleted or vnactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 198 (SEQ ID
N0:338). Two transmembrane domains have been tentatively identified as extending from about amino acid position 1 to about amino acid position 32, and from about amino acid position 195 through about amino acid position 2I7, in the PR01555 amino acid sequence (Figure 198, SEQ ID N0:338).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at Ieast about 95 %
positives when compared with the amino acid sequence of residues 32 to about 246, inclusive of Figure 198 (SEQ
ID N0:338); or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a 1PR01555 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments ~~re from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 io about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated :PROI555 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01555 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 to 246 of Figure 198 (SEQ ID N0:338).
In another aspect, the invention concerns an isolated PR01555 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 32 to about 246, .inclusive of Figure 198 (SEQ
ID N0:338).
In a further aspect, the invention concerns an isolated PR0155S polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 246 of Figure 198 (SEQ ID N0:338).
In yet another aspect, the invention concerns an isolated PR01555 polypeptide, comprising the sequence of amino acid residues 32 to about 246, inclusive of Figure 198. (SEQ ID
N0:338), or a fragment thereof sufficient to provide a binding site for an anti-PR01555 antibody. Preferably, the PRO1555 fragment retains a qualitative biological activity of a native PR01555 polypeptide.
In a still further aspect, the invention provides a poly~peptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01555 polypeptide having the sequence of amino acid residues from about 32 to about 246, inclusive of Figure 198 (SEQ ID N0:338), or (b) the complement of the DNA molecule of (a), and if the test DNA :molecule has at lease about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poIypeptide, and (iii) recovering the polypeptide from the cell culture.
100. PRO1485 A cDNA clone (DNA73746-1654) has been identified that encodes a novel polypeptide having sequence identity with lysozyme, and more particularly, lysozyme C precursor, and designated in the present application as "PR01485."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01485 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecae encoding a PR01485 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 148,, inclusive of Figure 200 (SEQ iD N0:340), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01485 polypeptide comprising DNA hybridizing to the complement of the. nucleic acid between about residues 20S and about 594, inclusive, of Figure 199 (SEQ ID N0:339). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203411 (DNA73746-1654), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature.polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203411 (DNA73746-1654).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 148, inclusive of Figure 200 (SEQ ID
N0:340), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01485 polypeptide having the sequence of amino acid residues from about 19 to about 148, inclusive of Figure 200 (SEQ
ID N0:340), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), iscolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 148, inclusive of Figure 200 (SEQ
ID N0:340), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01485 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated 1?R01485 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
la a specific aspect, the invention provides isolated native sequence PR01485 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 148 of Figure 200 (SEQ ID
N0:340).
In another aspect, the invention concerns an isolated PRO 1485 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 19 to about 148, inclusive of Figure 200 (SEQ
ID N0:340).
In a further aspect, the invention concerns an isolated PR01485 poiypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives; mast preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 through 148 of Figure 200 (SEQ ID N0:340).
In yet another aspect, the invention concerns an isolated PR0148S polypeptide, comprising the sequence of amino acid residues 19 to about 148, inclusive of Figure 200 (SEQ ID
N0:340), or a fragment thereof sufficient to provide a binding site for an anti-PR014$5 antibody. Preferably, the PR0148S fragment retains I0 a qualitative biological activity of a native PR01485 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01485 polypeptide having the sequence of amino acid residues from about 19 to about 148, inclusive of Figure 200 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence 1S identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01485 20 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01485 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01485 polypeptide, by contacting the native PR0148;5 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01485 polypeptide, 25 or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
101. PR01564 A cDNA clone {DNA73760-1672) has been identified, having homology to nucleic acid encoding an N-acetylgalactosaminyltransferase protein that encodes a novel pol;ypeptide, designated in the present application 30 as "PR01564".
In one embodiment, the invention provides an isolated nucleic acid molecute comprising DNA encoding a PR01564 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most 35 preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1S64 polypeptide having the sequence of amino acid residues from about 1 or about 29 to .about 639, inclusive of Figure 202 (SEQ ID
N0:347), or (b) the complement of the DNA molecule of (a).
wo aan27os PCT/US99/2a111 In another aspect, the invention concerns. an isolated nucleic acid molecule encoding a PRO1S64.
polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 462 or about S46 and about 2378, inclusive, of Figure 201 (SEQ ID~ N0:346}.
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having S at least about 80 % sequence identity, preferably at least about 8S %
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S'% sequence identity to (a) a DNA molecule encoding the same raature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203314 (DNA73760-1672) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature poiypeptide encoded by the human protein cDNA in ATCC Deposit No. 203314 (DNA73760-I672).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID
N0:347), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PRO1S64 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID N0:347), or {b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 9S % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1S64 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 202 (SEQ
ID N0:347). The transmembrane domain has been tentatively identified as extending from about amino acid position 11 to about amino acid position 36 in the PROIS64 amino acid sequence (Figure 202, SEQ ID N0:347).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID N0:347), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1S64 laolypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from albout 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more: preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 201 ~(SEQ ID N0:346}.
In another embodiment, the invention provides isolated PR01564 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specifc aspect, the invention provides isolated native sequence PRO1564 polypeptide, which in certain embodiments, includes an amino acid sequence comprising; residues I or about 29 to about 639 of Figure 202 (SEQ ID N0:347).
In another aspect, the invention concerns an isolated PRO1564 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or about 29 to about 639, inclusive of Figure 202 (SEQ ID N0:347).
In a further aspect, the invention concerns an isolated PR0~I564 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID
N0:347).
In yet another aspect, the invention concerns an isolated PRO1564 poIypeptide, comprising the sequence of amino acid residues l or about 29 to about 639, inclusive of Figure 202 (SEQ ID N0:347j, or a fragment thereof sufficient to provide a binding site for an anti-PR01564 antibody.
Preferably, the PR01564 fragment retains a qualitative biological activity of a native PR01564 polype;ptide.
In a still further aspect, the invention provides a polypeptiide produced by (ii) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01564 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 639, inclusive of Figure 202 (SEQ ID
N0:347), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable fir expression of the polypeptide, and (iii) recovering the poIypeptiide from the cell culture.
In yet another embodiment, the invention concerns agoni;sts and antagonists of a native PR01564 polypeptide. In a particular embodiment, the agonist or antagonist its an anti-PR01564 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01564 polypeptide by contacting the native PR01564 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01564 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
102. PR017S5 A cDNA clone (DNA76396-1698) has been identified that encodes a novel transmembrane polypeptide designated in the present application as "PR01755":
In one embodimem, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01755 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least.about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA mol!.ecule encoding a PR0175S polypeptide having S the sequence of amino acid residues from I or about 32 to about 276, inclusive of Figure 204 (SEQ ID N0:352), or (b) the complement of the DNA molecule of {a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01755 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1S 1 and about 885, inclusive, of Figure 203 (SEQ iD N0:351). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203471 IS (DNA76396-1598), or {b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide em;,oded by the human protein cDNA in ATCC
Deposit No. 203471 (DNA76396-1698).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to ;about 276, inclusive of Figure 204 (SEQ ID
N0:352), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a P7~01755 polygeptide having the sequence of amino acid residues from about 32 to about 276, inclusive of lFigure 204 {SEQ
iD N0:3S2), or (b) the complement of tile DNA molecule of (a), and, if the DNA molecule has ai least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01755 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domain deleted or inactivated), or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 2C~4 (SEQ ID
N0:352). The transmembrane domain has been tentatively identified as extending from about amino acid position 178 to about amino acid position 198 in the PROi755 amino acid sequence (Figure 204, SE~Q ID N0:352).
In another aspect, the invention concerns an isolated nucleic acid molecule compxising (a) DNA
r PCT/US99120I l i encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at lean: about 95%
positives when compared with the amino acid sequence of residues 32 to about 276, inclusive of Figure 204 (SEQ
ID N0:352), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01755 polypeptide coding sequence that may ftnd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to abort 40 nucleotides in length.
In another embodiment, the invention provides isolated PROI755 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01755 polypeptide, which in one embodiment, includes an amino acid sequence comgrising residuc;s 32 to 276 of Figure 204 (SEQ ID N0:352).
In another aspect, the invention concerns an isolated PRO 1755 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferable at least about 85% sequence identity, more preferably at least about 90% sequence identity, most greferabiy at least about 95% sequence identity to the sequence of amino acid residues 32 to about 276, inclusive of Figure 204 (SEQ
ID N0:352).
In a further aspect, the invention concerns an isolated PR01755 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 276 of Figure 204 (SEQ ID N0:352).
In yet another aspect, the invention concerns an isolated PR.O 1755 polypeptide, comprising the sequence of amino acid residues 32 to about 276, inclusive of Figure 204 (SEQ ID
N0:352), or a fragment thereof sufficient to provide a binding site for an anti-PR01755 antibody. Preferably, the PROI755 fragment retains a qualitative biological activity of a native PROi755 polygeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROi755 polypeptide having the sequence of amino acid residues from about 32 to about 276, inclusive of Figure 204 (SEQ ID N0:352), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more. preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression o~f the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01755 polypeptide. In a particular embodiraent, the agonist or antagonist is an anti-PR01755 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01755 polypeptide, by contacting the native PR01755 p~5lypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01755 polypeptide, CA 02339043 2001-02-14 v :::...:
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