Mammalian protein found in Homo sapiens
JAK1 Available structures PDB Ortholog search:PDBe RCSB List of PDB id codes 3EYG ,3EYH ,4E4L ,4E4N ,4E5W ,4EHZ ,4EI4 ,4FK6 ,4I5C ,4IVB ,4IVC ,4IVD ,4K6Z ,4K77 ,4L00 ,4L01 ,5E1E ,5HX8 ,5IXD ,5IXI
Identifiers Aliases JAK1 External IDs OMIM :147795 ;MGI :96628 ;HomoloGene :1678 ;GeneCards :JAK1 ;OMA :JAK1 - orthologs Wikidata
Janus kinase 1 (JAK1) is a humantyrosine kinase protein essential for signaling for certain type I and type IIcytokines . It interacts with thecommon gamma chain (γc) oftype I cytokine receptors , to elicit signals from theIL-2 receptor family (e.g.IL-2R ,IL-7R ,IL-9R andIL-15R ), theIL-4 receptor family (e.g.IL-4R andIL-13R ), thegp130 receptor family (e.g.IL-6R ,IL-11R ,LIF-R ,OSM-R ,cardiotrophin-1 receptor (CT-1R),ciliary neurotrophic factor receptor (CNTF-R),neurotrophin-1 receptor (NNT-1R) andLeptin-R ). It is also important for transducing a signal by type I (IFN-α /β ) and type II (IFN-γ )interferons , and members of theIL-10 family viatype II cytokine receptors .[ 5] [ 6] metastasize to other parts of the body.[ 7]
Janus kinase 1 has been shown tointeract with:
ELP2 ,[ 8] GNB2L1 [ 9] IL6ST ,[ 10] [ 11] [ 12] Grb2 ,[ 13] [ 14] IL2RB ,[ 15] [ 16] [ 17] [ 18] [ 19] IRS1 ,[ 20] [ 21] IL10RA ,[ 15] [ 22] PTPN11 ,[ 23] [ 24] STAM2 ,[ 25] [ 26] STAT3 ,[ 27] [ 28] STAT5A ,[ 29] STAT5B ,[ 29] TNFRSF1A .[ 30] [ 31] ^a b c GRCh38: Ensembl release 89: ENSG00000162434 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000028530 –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 .^ Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A, Zhou YJ, et al. (2001)."Signaling by type I and II cytokine receptors: ten years after" .Curr. Opin. Immunol .13 (3):363– 73.doi :10.1016/S0952-7915(00)00228-4 .PMID 11406370 . ^ Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, et al. (1998)."Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses" .Cell .93 (3):373– 83.doi :10.1016/S0092-8674(00)81166-6 PMID 9590172 .S2CID 18684846 . ^ Christian Nordqvist."Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor" .Medical News Today . ^ Collum RG, Brutsaert S, Lee G, Schindler C (August 2000)."A Stat3-interacting protein (StIP1) regulates cytokine signal transduction" .Proc. Natl. Acad. Sci. U.S.A .97 (18):10120– 5.Bibcode :2000PNAS...9710120C .doi :10.1073/pnas.170192197 PMC 27739 PMID 10954736 . ^ Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR (September 2003)."The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex" .J. Immunol .171 (6):2989– 94.doi :10.4049/jimmunol.171.6.2989 PMID 12960323 . ^ Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, et al. (October 2001)."Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction" .J. Biol. Chem .276 (40):37451– 8.doi :10.1074/jbc.M106135200 PMID 11468294 . ^ Kim H, Baumann H (December 1997)."Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells" .J. Biol. Chem .272 (49):30741– 7.doi :10.1074/jbc.272.49.30741 PMID 9388212 . ^ Haan C, Heinrich PC, Behrmann I (January 2002)."Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation" .Biochem. J .361 (Pt 1):105– 11.doi :10.1042/0264-6021:3610105 .PMC 1222284 PMID 11742534 . ^ Kim H, Lee YH, Won J, Yun Y (September 2001). "Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers".Biochem. Biophys. Res. Commun .286 (5):886– 94.Bibcode :2001BBRC..286..886K .doi :10.1006/bbrc.2001.5496 .PMID 11527382 . ^ Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (December 1995)."Involvement of Janus kinases in the insulin signaling pathway" .Eur. J. Biochem .234 (2):656– 60.doi :10.1111/j.1432-1033.1995.656_b.x PMID 8536716 . ^a b Usacheva A, Kotenko S, Witte MM, Colamonici OR (August 2002)."Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors" .J. Immunol .169 (3):1302– 8.doi :10.4049/jimmunol.169.3.1302 PMID 12133952 . ^ Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, et al. (November 1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits".Science .266 (5187):1045– 7.Bibcode :1994Sci...266.1045M .doi :10.1126/science.7973659 .PMID 7973659 . ^ Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, et al. (November 1994)."Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID" .Science .266 (5187):1042– 5.Bibcode :1994Sci...266.1042R .doi :10.1126/science.7973658 .PMID 7973658 . ^ Zhu MH, Berry JA, Russell SM, Leonard WJ (April 1998)."Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta" .J. Biol. Chem .273 (17):10719– 25.doi :10.1074/jbc.273.17.10719 PMID 9553136 . ^ Migone TS, Rodig S, Cacalano NA, Berg M, Schreiber RD, Leonard WJ (November 1998)."Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation" .Mol. Cell. Biol .18 (11):6416– 22.doi :10.1128/mcb.18.11.6416 .PMC 109227 PMID 9774657 . ^ Gual P, Baron V, Lequoy V, Van Obberghen E (March 1998)."Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor" .Endocrinology .139 (3):884– 93.doi :10.1210/endo.139.3.5829 PMID 9492017 . ^ Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, et al. (December 1995)."Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases" .J. Biol. Chem .270 (48):28527– 30.doi :10.1074/jbc.270.48.28527 PMID 7499365 . ^ Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, et al. (December 2002)."Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation" .J. Biol. Chem .277 (50):48220– 6.doi :10.1074/jbc.M205757200 PMID 12374810 . ^ Yin T, Shen R, Feng GS, Yang YC (January 1997)."Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases" .J. Biol. Chem .272 (2):1032– 7.doi :10.1074/jbc.272.2.1032 PMID 8995399 . ^ Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, et al. (January 2003)."SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130" .J. Biol. Chem .278 (1):661– 71.doi :10.1074/jbc.M210552200 PMID 12403768 . ^ Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, et al. (December 2000)."Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways" .J. Biol. Chem .275 (49):38633– 9.doi :10.1074/jbc.M007849200 PMID 10993906 . ^ Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, et al. (July 2000)."STAM2, a new member of the STAM family, binding to the Janus kinases" .FEBS Lett .477 (1– 2):55– 61.Bibcode :2000FEBSL.477...55E .doi :10.1016/s0014-5793(00)01760-9 PMID 10899310 . ^ Ueda T, Bruchovsky N, Sadar MD (March 2002)."Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways" .J. Biol. Chem .277 (9):7076– 85.doi :10.1074/jbc.M108255200 PMID 11751884 . ^ Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F (August 2001). "Constitutive activation of STAT transcription factors in acute myelogenous leukemia".Eur. J. Haematol .67 (2):63– 71.doi :10.1034/j.1600-0609.2001.t01-1-00385.x .PMID 11722592 .S2CID 38074766 . ^a b Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, et al. (February 1997)."An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT" .Oncogene .14 (7):751– 61.doi :10.1038/sj.onc.1200907 PMID 9047382 . ^ Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB (March 1998)."Induction of Jak/STAT signaling by activation of the type 1 TNF receptor" .J. Immunol .160 (6):2742– 50.doi :10.4049/jimmunol.160.6.2742 PMID 9510175 . ^ Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, et al. (January 2002). "Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells".Cell Growth Differ .13 (1):13– 8.PMID 11801527 . Donnelly RP, Dickensheets H, Finbloom DS (1999)."The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes" .J. Interferon Cytokine Res .19 (6):563– 73.doi :10.1089/107999099313695 .PMID 10433356 . Carter-Su C, Rui L, Stofega MR (2000). "SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone".Recent Prog. Horm. Res .55 :293– 311.PMID 11036942 . Kostrodymova GM (1976). "[An experimental study of the possible sensitizing properties of triethanolamine contained in chemical compounds used at home]".Gigiena i Sanitariia (6):10– 2.PMID 1213395 . Howard OM, Dean M, Young H, Ramsburg M, Turpin JA, Michiel DF, et al. (1992). "Characterization of a class 3 tyrosine kinase".Oncogene .7 (5):895– 900.PMID 1373877 . Pritchard MA, Baker E, Callen DF, Sutherland GR, Wilks AF (1992). "Two members of the JAK family of protein tyrosine kinases map to chromosomes 1p31.3 and 9p24".Mamm. Genome .3 (1):36– 8.doi :10.1007/BF00355839 .PMID 1581631 .S2CID 31384629 . Wilks AF, Harpur AG, Kurban RR, Ralph SJ, Zürcher G, Ziemiecki A (1991)."Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase" .Mol. Cell. Biol .11 (4):2057– 65.doi :10.1128/MCB.11.4.2057 .PMC 359893 PMID 1848670 . Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, et al. (1996)."Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases" .J. Biol. Chem .270 (48):28527– 30.doi :10.1074/jbc.270.48.28527 PMID 7499365 . Nicholson SE, Oates AC, Harpur AG, Ziemiecki A, Wilks AF, Layton JE (1994)."Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation" .Proc. Natl. Acad. Sci. U.S.A .91 (8):2985– 8.Bibcode :1994PNAS...91.2985N .doi :10.1073/pnas.91.8.2985 PMC 43499 PMID 7512720 . Domanski P, Yan H, Witte MM, Krolewski J, Colamonici OR (1995)."Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase" .FEBS Lett .374 (3):317– 22.Bibcode :1995FEBSL.374..317D .doi :10.1016/0014-5793(95)01094-U PMID 7589562 . Modi WS, Farrar WL, Howard OM (1995)."Confirmed assignment of a novel human tyrosine kinase gene (JAK1A) to 1p32.3→p31.3 by nonisotopic in situ hybridization" .Cytogenet. Cell Genet .69 (3– 4):232– 4.doi :10.1159/000133971 .PMID 7698020 . Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu Z, et al. (1994). "Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits".Science .266 (5187):1045– 7.Bibcode :1994Sci...266.1045M .doi :10.1126/science.7973659 .PMID 7973659 . Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, et al. (1993). "The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction".Nature .366 (6451):129– 35.Bibcode :1993Natur.366..129M .doi :10.1038/366129a0 .PMID 8232552 .S2CID 27334189 . Lee ST, Strunk KM, Spritz RA (1993). "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes".Oncogene .8 (12):3403– 10.PMID 8247543 . Lütticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, et al. (1994). "Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130".Science .263 (5143):89– 92.Bibcode :1994Sci...263...89L .doi :10.1126/science.8272872 .PMID 8272872 . Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E (1996)."Involvement of Janus kinases in the insulin signaling pathway" .Eur. J. Biochem .234 (2):656– 60.doi :10.1111/j.1432-1033.1995.656_b.x PMID 8536716 . Friedmann MC, Migone TS, Russell SM, Leonard WJ (1996)."Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation" .Proc. Natl. Acad. Sci. U.S.A .93 (5):2077– 82.Bibcode :1996PNAS...93.2077F .doi :10.1073/pnas.93.5.2077 PMC 39912 PMID 8700888 . Gauzzi MC, Velazquez L, McKendry R, Mogensen KE, Fellous M, Pellegrini S (1996)."Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase" .J. Biol. Chem .271 (34):20494– 500.doi :10.1074/jbc.271.34.20494 PMID 8702790 . Demoulin JB, Uyttenhove C, Van Roost E, Delestré B, Donckers D, Van Snick J, et al. (1996)."A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9" .Mol. Cell. Biol .16 (9):4710– 6.doi :10.1128/MCB.16.9.4710 .PMC 231471 PMID 8756628 . Yin T, Shen R, Feng GS, Yang YC (1997)."Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases" .J. Biol. Chem .272 (2):1032– 7.doi :10.1074/jbc.272.2.1032 PMID 8995399 . Bluyssen HA, Levy DE (1997)."Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA" .J. Biol. Chem .272 (7):4600– 5.doi :10.1074/jbc.272.7.4600 PMID 9020188 .
Activity Regulation Classification Kinetics Types
Chemokine CSF
Interferon
IFNAR (α/β, I) Agonists: Albinterferon Interferon alpha (interferon alfa, IFN-α) Interferon alfa (IFNA1 ,IFNA2 ,IFNA4 ,IFNA5 ,IFNA6 ,IFNA7 ,IFNA8 ,IFNA10 ,IFNA13 ,IFNA14 ,IFNA16 ,IFNA17 ,IFNA21 )Interferon alfa 2a Interferon alfa 2b Interferon alfa n1 Interferon alfacon-1 Interferon alpha-n3 Interferon beta (IFN-β) (IFNB1 ,IFNB3 )Interferon beta 1a Interferon beta 1b Interferon kappa (IFN-ε/κ/τ/ζ, IFNK) Interferon omega (IFN-ω, IFNW1) Peginterferon alfa-2a Peginterferon alfa-2b IFNGR (γ, II) IFNLR (λ, III) See IL-28R (IFNLR)here instead.
Interleukin TGFβ TNF Others
