Protein found in humans
Pre-B-cell leukemia transcription factor 1 is aprotein that in humans is encoded by thePBX1 gene .[ 5] extradenticle , and causes changes in embryonic development.
Mice studies suggest PBX1 is involved in bone generation and skeletal patterning.[ 6]
PBX1 has been shown tointeract with:
TheDrosophila melangoster extradenticle encodes a homeodomain protein that is 71% similar to the Pbx1 protein, and is considered homologous to PBX1.[ 14] homeodomain transcription factor [ 15] embryogenesis and is related to morphological changes and development.[ 14]
Reduced levels of extradenticle cause segmental transformations, without affecting the functionality or location ofhomeotic genes. Complete removal of extradenticle both maternally and zygotically leads to alterations from failure of non-extradenticle protein expression.[ 16]
A monoclonal antibody study of the expression of extradenticle protein in embryonic development found that it is uniformly distributed, as well as excluded from cell nuclei, untilgastrulation . During the germ band retraction stage of development, extradenticle protein begins to accumulate in the nuclei of cells in a specific pattern. Proximal areas of wing and legimaginal discs have extradenticle present in the nucleus, while distal areas only have it in the cytoplasm.[ 17]
^a b c GRCh38: Ensembl release 89: ENSG00000185630 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000052534 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Entrez Gene: PBX1 Pre-B-cell leukemia homeobox 1" .^ "PBX1 PBX homeobox 1 [Homo sapiens (human)] - Gene - NCBI" .www.ncbi.nlm.nih.gov . Retrieved2023-06-11 .^ Berthelsen J, Zappavigna V, Ferretti E, Mavilio F, Blasi F (March 1998)."The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity" .The EMBO Journal .17 (5):1434– 1445.doi :10.1093/emboj/17.5.1434 .PMC 1170491 PMID 9482740 . ^ Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C (February 1999)."Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation" .Cell .96 (4):587– 597.doi :10.1016/S0092-8674(00)80662-5 PMID 10052460 .S2CID 16122785 . ^ Chang CP, Shen WF, Rozenfeld S, Lawrence HJ, Largman C, Cleary ML (March 1995)."Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins" .Genes & Development .9 (6):663– 674.doi :10.1101/gad.9.6.663 PMID 7729685 . ^ Shen WF, Rozenfeld S, Kwong A, Köm ves LG, Lawrence HJ, Largman C (April 1999)."HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells" .Molecular and Cellular Biology .19 (4):3051– 3061.doi :10.1128/MCB.19.4.3051 .PMC 84099 PMID 10082572 . ^ Shanmugam K, Green NC, Rambaldi I, Saragovi HU, Featherstone MS (November 1999)."PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins" .Molecular and Cellular Biology .19 (11):7577– 7588.doi :10.1128/MCB.19.11.7577 .PMC 84774 PMID 10523646 . ^ Jacobs Y, Schnabel CA, Cleary ML (July 1999)."Trimeric association of Hox and TALE homeodomain proteins mediates Hoxb2 hindbrain enhancer activity" .Molecular and Cellular Biology .19 (7):5134– 5142.doi :10.1128/MCB.19.7.5134 .PMC 84356 PMID 10373562 . ^ Zubair M, Ishihara S, Oka S, Okumura K, Morohashi K (June 2006)."Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1" .Molecular and Cellular Biology .26 (11):4111– 4121.doi :10.1128/MCB.00222-06 .PMC 1489093 PMID 16705164 . ^a b Rauskolb C, Peifer M, Wieschaus E (September 1993). "extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1".Cell .74 (6):1101– 1112.doi :10.1016/0092-8674(93)90731-5 .PMID 8104703 .S2CID 44721382 . ^ Aspland SE, White RA (February 1997). "Nucleocytoplasmic localisation of extradenticle protein is spatially regulated throughout development in Drosophila".Development .124 (3):741– 747.doi :10.1242/dev.124.3.741 .PMID 9043089 . ^ Peifer M, Wieschaus E (July 1990)."Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity" .Genes & Development .4 (7):1209– 1223.doi :10.1101/gad.4.7.1209 PMID 1976570 . ^ Aspland SE, White RA (1997)."Nucleocytoplasmic localisation of extradenticle protein is spatially regulated throughout development in Drosophila" Development .124 (3):741– 747.doi :10.1242/dev.124.3.741 .PMID 9043089 . Retrieved2023-06-06 . Sanyal M, Tung JW, Karsunky H, Zeng H, Selleri L, Weissman IL, et al. (May 2007)."B-cell development fails in the absence of the Pbx1 proto-oncogene" .Blood .109 (10):4191– 4199.doi :10.1182/blood-2006-10-054213 .PMC 1885499 PMID 17244677 . {{cite journal }}: CS1 maint: overridden setting (link )Hui H, Perfetti R (February 2002)."Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood" .European Journal of Endocrinology .146 (2):129– 141.doi :10.1530/eje.0.1460129 PMID 11834421 . Hunger SP, Galili N, Carroll AJ, Crist WM, Link MP, Cleary ML (February 1991)."The t(1;19)(q23;p13) results in consistent fusion of E2A and PBX1 coding sequences in acute lymphoblastic leukemias" .Blood .77 (4):687– 693.doi :10.1182/blood.V77.4.687.687 PMID 1671560 . Monica K, Galili N, Nourse J, Saltman D, Cleary ML (December 1991)."PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1" .Molecular and Cellular Biology .11 (12):6149– 6157.doi :10.1128/mcb.11.12.6149 .PMC 361792 PMID 1682799 . Nourse J, Mellentin JD, Galili N, Wilkinson J, Stanbridge E, Smith SD, et al. (February 1990)."Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor" .Cell .60 (4):535– 545.doi :10.1016/0092-8674(90)90657-Z PMID 1967982 .S2CID 7975269 . Kamps MP, Murre C, Sun XH, Baltimore D (February 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL".Cell .60 (4):547– 555.doi :10.1016/0092-8674(90)90658-2 .PMID 1967983 .S2CID 39661371 . Lu Q, Wright DD, Kamps MP (June 1994)."Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation" .Molecular and Cellular Biology .14 (6):3938– 3948.doi :10.1128/mcb.14.6.3938 .PMC 358760 PMID 7910944 . Van Dijk MA, Voorhoeve PM, Murre C (July 1993)."Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia" .Proceedings of the National Academy of Sciences of the United States of America .90 (13):6061– 6065.Bibcode :1993PNAS...90.6061D .doi :10.1073/pnas.90.13.6061 PMC 46867 PMID 8327485 . Lu Q, Kamps MP (April 1996)."Structural determinants within Pbx1 that mediate cooperative DNA binding with pentapeptide-containing Hox proteins: proposal for a model of a Pbx1-Hox-DNA complex" .Molecular and Cellular Biology .16 (4):1632– 1640.doi :10.1128/mcb.16.4.1632 .PMC 231149 PMID 8657138 . Berthelsen J, Zappavigna V, Mavilio F, Blasi F (March 1998)."Prep1, a novel functional partner of Pbx proteins" .The EMBO Journal .17 (5):1423– 1433.doi :10.1093/emboj/17.5.1423 .PMC 1170490 PMID 9482739 . Berthelsen J, Zappavigna V, Ferretti E, Mavilio F, Blasi F (March 1998)."The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity" .The EMBO Journal .17 (5):1434– 1445.doi :10.1093/emboj/17.5.1434 .PMC 1170491 PMID 9482740 . Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C (February 1999)."Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation" .Cell .96 (4):587– 597.doi :10.1016/S0092-8674(00)80662-5 PMID 10052460 .S2CID 16122785 . Shen WF, Rozenfeld S, Kwong A, Köm ves LG, Lawrence HJ, Largman C (April 1999)."HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells" .Molecular and Cellular Biology .19 (4):3051– 3061.doi :10.1128/MCB.19.4.3051 .PMC 84099 PMID 10082572 . Jacobs Y, Schnabel CA, Cleary ML (July 1999)."Trimeric association of Hox and TALE homeodomain proteins mediates Hoxb2 hindbrain enhancer activity" .Molecular and Cellular Biology .19 (7):5134– 5142.doi :10.1128/MCB.19.7.5134 .PMC 84356 PMID 10373562 . Knoepfler PS, Bergstrom DA, Uetsuki T, Dac-Korytko I, Sun YH, Wright WE, et al. (September 1999)."A conserved motif N-terminal to the DNA-binding domains of myogenic bHLH transcription factors mediates cooperative DNA binding with pbx-Meis1/Prep1" .Nucleic Acids Research .27 (18):3752– 3761.doi :10.1093/nar/27.18.3752 .PMC 148632 PMID 10471746 . {{cite journal }}: CS1 maint: overridden setting (link )McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR, Murre C (September 1999)."Oncogenic homeodomain transcription factor E2A-Pbx1 activates a novel WNT gene in pre-B acute lymphoblastoid leukemia" .Proceedings of the National Academy of Sciences of the United States of America .96 (20):11464– 11469.Bibcode :1999PNAS...9611464M .doi :10.1073/pnas.96.20.11464 PMC 18056 PMID 10500199 . Shanmugam K, Green NC, Rambaldi I, Saragovi HU, Featherstone MS (November 1999)."PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins" .Molecular and Cellular Biology .19 (11):7577– 7588.doi :10.1128/MCB.19.11.7577 .PMC 84774 PMID 10523646 . Mikkola I, Bruun JA, Holm T, Johansen T (February 2001)."Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins" .The Journal of Biological Chemistry .276 (6):4109– 4118.doi :10.1074/jbc.M008882200 PMID 11069920 . Thameem F, Wolford JK, Bogardus C, Prochazka M (March 2001). "Analysis of PBX1 as a candidate gene for type 2 diabetes mellitus in Pima Indians".Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression .1518 (1– 2):215– 220.doi :10.1016/S0167-4781(01)00189-0 .PMID 11267683 . Liu Y, MacDonald RJ, Swift GH (May 2001)."DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex" .The Journal of Biological Chemistry .276 (21):17985– 17993.doi :10.1074/jbc.M100678200 PMID 11279116 . Mal A, Sturniolo M, Schiltz RL, Ghosh MK, Harter ML (April 2001)."A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program" .The EMBO Journal .20 (7):1739– 1753.doi :10.1093/emboj/20.7.1739 .PMC 145490 PMID 11285237 .
PDB gallery
1b72 : PBX1, HOMEOBOX PROTEIN HOX-B1/DNA TERNARY COMPLEX
1b8i : STRUCTURE OF THE HOMEOTIC UBX/EXD/DNA TERNARY COMPLEX
1du6 : SOLUTION STRUCTURE OF THE TRUNCATED PBX HOMEODOMAIN
1lfu : NMR solution structure of the extended PBX homeodomain bound to DNA
1puf : Crystal structure of HoxA9 and Pbx1 homeodomains bound to DNA
(1) Basic domains
(1.1) Basic leucine zipper (bZIP )(1.2) Basic helix-loop-helix (bHLH )
Group A Group B Group CPAS Group D Group E Group F
(1.3) bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2.1) Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4)β-Scaffold factors with minor groove contacts
(0) Other transcription factors
