Tyrosine-protein kinase JAK2

Details

Name
Tyrosine-protein kinase JAK2
Synonyms
  • 2.7.10.2
  • JAK-2
  • Janus kinase 2
Gene Name
JAK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021326|Tyrosine-protein kinase JAK2
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSG
EYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYF
PRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG
MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQF
SQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSR
GKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR
EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQT
GLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNC
YQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI
RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASM
MSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWA
MHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP
PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAEL
ANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRD
PTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE
ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQI
CKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFW
YAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIE
LLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG
Number of residues
1132
Molecular Weight
130672.475
Theoretical pI
7.21
GO Classification
Functions
ATP binding / growth hormone receptor binding / heme binding / histone binding / histone kinase activity (H3-Y41 specific) / interleukin-12 receptor binding / non-membrane spanning protein tyrosine kinase activity / protein kinase activity / protein kinase binding / protein tyrosine kinase activity / receptor binding / SH2 domain binding
Processes
actin filament polymerization / activation of cysteine-type endopeptidase activity involved in apoptotic process / activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / activation of JAK2 kinase activity / activation of MAPKK activity / adaptive immune response / apoptotic process / axon guidance / axon regeneration / blood coagulation / cell differentiation / cell migration / cellular response to dexamethasone stimulus / cellular response to lipopolysaccharide / chromatin organization / cytokine-mediated signaling pathway / enzyme linked receptor protein signaling pathway / epidermal growth factor receptor signaling pathway / erythrocyte differentiation / extrinsic apoptotic signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / G-protein coupled receptor signaling pathway / growth hormone receptor signaling pathway / histone H3-Y41 phosphorylation / hormone-mediated signaling pathway / host programmed cell death induced by symbiont / innate immune response / insulin receptor signaling pathway / interferon-gamma-mediated signaling pathway / interleukin-12-mediated signaling pathway / intracellular signal transduction / intrinsic apoptotic signaling pathway in response to oxidative stress / JAK-STAT cascade / JAK-STAT cascade involved in growth hormone signaling pathway / mammary gland epithelium development / MAPK cascade / mesoderm development / mineralocorticoid receptor signaling pathway / movement of cell or subcellular component / negative regulation of cardiac muscle cell apoptotic process / negative regulation of cell proliferation / negative regulation of cell-cell adhesion / negative regulation of DNA binding / negative regulation of heart contraction / negative regulation of neuron apoptotic process / neurotrophin TRK receptor signaling pathway / peptidyl-tyrosine autophosphorylation / peptidyl-tyrosine phosphorylation / platelet-derived growth factor receptor signaling pathway / positive regulation of cell activation / positive regulation of cell differentiation / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cell-substrate adhesion / positive regulation of cytosolic calcium ion concentration / positive regulation of DNA binding / positive regulation of growth hormone receptor signaling pathway / positive regulation of inflammatory response / positive regulation of insulin secretion / positive regulation of interleukin-1 beta production / positive regulation of nitric oxide biosynthetic process / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of phosphoprotein phosphatase activity / positive regulation of protein import into nucleus, translocation / positive regulation of sequence-specific DNA binding transcription factor activity / positive regulation of transcription from RNA polymerase II promoter / positive regulation of tumor necrosis factor production / positive regulation of tyrosine phosphorylation of Stat3 protein / positive regulation of tyrosine phosphorylation of Stat5 protein / protein autophosphorylation / protein phosphorylation / Ras protein signal transduction / regulation of apoptotic process / regulation of cell proliferation / regulation of inflammatory response / regulation of interferon-gamma-mediated signaling pathway / response to antibiotic / response to hydroperoxide / response to interleukin-12 / response to lipopolysaccharide / response to tumor necrosis factor / signal transduction / small GTPase mediated signal transduction / STAT protein import into nucleus / tumor necrosis factor-mediated signaling pathway / tyrosine phosphorylation of STAT protein / tyrosine phosphorylation of Stat1 protein / tyrosine phosphorylation of Stat3 protein / tyrosine phosphorylation of Stat5 protein / vascular endothelial growth factor receptor signaling pathway
Components
caveola / cytoplasm / cytoskeleton / cytosol / endosome lumen / extrinsic component of cytoplasmic side of plasma membrane / membrane raft / nuclear matrix / nucleoplasm / nucleus
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Endomembrane system
Gene sequence
>lcl|BSEQ0021327|Tyrosine-protein kinase JAK2 (JAK2)
ATGGGAATGGCCTGCCTTACGATGACAGAAATGGAGGGAACATCCACCTCTTCTATATAT
CAGAATGGTGATATTTCTGGAAATGCCAATTCTATGAAGCAAATAGATCCAGTTCTTCAG
GTGTATCTTTACCATTCCCTTGGGAAATCTGAGGCAGATTATCTGACCTTTCCATCTGGG
GAGTATGTTGCAGAAGAAATCTGTATTGCTGCTTCTAAAGCTTGTGGTATCACACCTGTG
TATCATAATATGTTTGCTTTAATGAGTGAAACAGAAAGGATCTGGTATCCACCCAACCAT
GTCTTCCATATAGATGAGTCAACCAGGCATAATGTACTCTACAGAATAAGATTTTACTTT
CCTCGTTGGTATTGCAGTGGCAGCAACAGAGCCTATCGGCATGGAATATCTCGAGGTGCT
GAAGCTCCTCTTCTTGATGACTTTGTCATGTCTTACCTCTTTGCTCAGTGGCGGCATGAT
TTTGTGCACGGATGGATAAAAGTACCTGTGACTCATGAAACACAGGAAGAATGTCTTGGG
ATGGCAGTGTTAGATATGATGAGAATAGCCAAAGAAAACGATCAAACCCCACTGGCCATC
TATAACTCTATCAGCTACAAGACATTCTTACCAAAATGTATTCGAGCAAAGATCCAAGAC
TATCATATTTTGACAAGGAAGCGAATAAGGTACAGATTTCGCAGATTTATTCAGCAATTC
AGCCAATGCAAAGCCACTGCCAGAAACTTGAAACTTAAGTATCTTATAAATCTGGAAACT
CTGCAGTCTGCCTTCTACACAGAGAAATTTGAAGTAAAAGAACCTGGAAGTGGTCCTTCA
GGTGAGGAGATTTTTGCAACCATTATAATAACTGGAAACGGTGGAATTCAGTGGTCAAGA
GGGAAACATAAAGAAAGTGAGACACTGACAGAACAGGATTTACAGTTATATTGCGATTTT
CCTAATATTATTGATGTCAGTATTAAGCAAGCAAACCAAGAGGGTTCAAATGAAAGCCGA
GTTGTAACTATCCATAAGCAAGATGGTAAAAATCTGGAAATTGAACTTAGCTCATTAAGG
GAAGCTTTGTCTTTCGTGTCATTAATTGATGGATATTATAGATTAACTGCAGATGCACAT
CATTACCTCTGTAAAGAAGTAGCACCTCCAGCCGTGCTTGAAAATATACAAAGCAACTGT
CATGGCCCAATTTCGATGGATTTTGCCATTAGTAAACTGAAGAAAGCAGGTAATCAGACT
GGACTGTATGTACTTCGATGCAGTCCTAAGGACTTTAATAAATATTTTTTGACTTTTGCT
GTCGAGCGAGAAAATGTCATTGAATATAAACACTGTTTGATTACAAAAAATGAGAATGAA
GAGTACAACCTCAGTGGGACAAAGAAGAACTTCAGCAGTCTTAAAGATCTTTTGAATTGT
TACCAGATGGAAACTGTTCGCTCAGACAATATAATTTTCCAGTTTACTAAATGCTGTCCC
CCAAAGCCAAAAGATAAATCAAACCTTCTAGTCTTCAGAACGAATGGTGTTTCTGATGTA
CCAACCTCACCAACATTACAGAGGCCTACTCATATGAACCAAATGGTGTTTCACAAAATC
AGAAATGAAGATTTGATATTTAATGAAAGCCTTGGCCAAGGCACTTTTACAAAGATTTTT
AAAGGCGTACGAAGAGAAGTAGGAGACTACGGTCAACTGCATGAAACAGAAGTTCTTTTA
AAAGTTCTGGATAAAGCACACAGAAACTATTCAGAGTCTTTCTTTGAAGCAGCAAGTATG
ATGAGCAAGCTTTCTCACAAGCATTTGGTTTTAAATTATGGAGTATGTGTCTGTGGAGAC
GAGAATATTCTGGTTCAGGAGTTTGTAAAATTTGGATCACTAGATACATATCTGAAAAAG
AATAAAAATTGTATAAATATATTATGGAAACTTGAAGTTGCTAAACAGTTGGCATGGGCC
ATGCATTTTCTAGAAGAAAACACCCTTATTCATGGGAATGTATGTGCCAAAAATATTCTG
CTTATCAGAGAAGAAGACAGGAAGACAGGAAATCCTCCTTTCATCAAACTTAGTGATCCT
GGCATTAGTATTACAGTTTTGCCAAAGGACATTCTTCAGGAGAGAATACCATGGGTACCA
CCTGAATGCATTGAAAATCCTAAAAATTTAAATTTGGCAACAGACAAATGGAGTTTTGGT
ACCACTTTGTGGGAAATCTGCAGTGGAGGAGATAAACCTCTAAGTGCTCTGGATTCTCAA
AGAAAGCTACAATTTTATGAAGATAGGCATCAGCTTCCTGCACCAAAGTGGGCAGAATTA
GCAAACCTTATAAATAATTGTATGGATTATGAACCAGATTTCAGGCCTTCTTTCAGAGCC
ATCATACGAGATCTTAACAGTTTGTTTACTCCAGATTATGAACTATTAACAGAAAATGAC
ATGTTACCAAATATGAGGATAGGTGCCCTGGGGTTTTCTGGTGCCTTTGAAGACCGGGAT
CCTACACAGTTTGAAGAGAGACATTTGAAATTTCTACAGCAACTTGGCAAGGGTAATTTT
GGGAGTGTGGAGATGTGCCGGTATGACCCTCTACAGGACAACACTGGGGAGGTGGTCGCT
GTAAAAAAGCTTCAGCATAGTACTGAAGAGCACCTAAGAGACTTTGAAAGGGAAATTGAA
ATCCTGAAATCCCTACAGCATGACAACATTGTAAAGTACAAGGGAGTGTGCTACAGTGCT
GGTCGGCGTAATCTAAAATTAATTATGGAATATTTACCATATGGAAGTTTACGAGACTAT
CTTCAAAAACATAAAGAACGGATAGATCACATAAAACTTCTGCAGTACACATCTCAGATA
TGCAAGGGTATGGAGTATCTTGGTACAAAAAGGTATATCCACAGGGATCTGGCAACGAGA
AATATATTGGTGGAGAACGAGAACAGAGTTAAAATTGGAGATTTTGGGTTAACCAAAGTC
TTGCCACAAGACAAAGAATACTATAAAGTAAAAGAACCTGGTGAAAGTCCCATATTCTGG
TATGCTCCAGAATCACTGACAGAGAGCAAGTTTTCTGTGGCCTCAGATGTTTGGAGCTTT
GGAGTGGTTCTGTATGAACTTTTCACATACATTGAGAAGAGTAAAAGTCCACCAGCGGAA
TTTATGCGTATGATTGGCAATGACAAACAAGGACAGATGATCGTGTTCCATTTGATAGAA
CTTTTGAAGAATAATGGAAGATTACCAAGACCAGATGGATGCCCAGATGAGATCTATATG
ATCATGACAGAATGCTGGAACAATAATGTAAATCAACGCCCCTCCTTTAGGGATCTAGCT
CTTCGAGTGGATCAAATAAGGGATAACATGGCTGGATGA
Chromosome Location
9
Locus
9p24
External Identifiers
ResourceLink
UniProtKB IDO60674
UniProtKB Entry NameJAK2_HUMAN
GenBank Gene IDAF058925
GenAtlas IDJAK2
HGNC IDHGNC:6192
General References
  1. Saltzman A, Stone M, Franks C, Searfoss G, Munro R, Jaye M, Ivashchenko Y: Cloning and characterization of human Jak-2 kinase: high mRNA expression in immune cells and muscle tissue. Biochem Biophys Res Commun. 1998 May 29;246(3):627-33. [Article]
  2. Dalal I, Arpaia E, Dadi H, Kulkarni S, Squire J, Roifman CM: Cloning and characterization of the human homolog of mouse Jak2. Blood. 1998 Feb 1;91(3):844-51. [Article]
  3. Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P: Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood. 1997 Oct 1;90(7):2535-40. [Article]
  4. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  5. Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S: The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. J Biol Chem. 1999 Oct 29;274(44):31531-42. [Article]
  6. Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K: STAM2, a new member of the STAM family, binding to the Janus kinases. FEBS Lett. 2000 Jul 14;477(1-2):55-61. [Article]
  7. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW: A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002 Jun 1;168(11):5699-708. [Article]
  8. Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC: The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res. 2005 Apr 1;65(7):2662-7. [Article]
  9. Murati A, Gelsi-Boyer V, Adelaide J, Perot C, Talmant P, Giraudier S, Lode L, Letessier A, Delaval B, Brunel V, Imbert M, Garand R, Xerri L, Birnbaum D, Mozziconacci MJ, Chaffanet M: PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia. 2005 Sep;19(9):1692-6. [Article]
  10. Bousquet M, Quelen C, De Mas V, Duchayne E, Roquefeuil B, Delsol G, Laurent G, Dastugue N, Brousset P: The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene. 2005 Nov 3;24(48):7248-52. [Article]
  11. Bacher U, Reiter A, Haferlach T, Mueller L, Schnittger S, Kern W, Schoch C: A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia. Haematologica. 2006 Jun;91(6):817-20. [Article]
  12. Adelaide J, Perot C, Gelsi-Boyer V, Pautas C, Murati A, Copie-Bergman C, Imbert M, Chaffanet M, Birnbaum D, Mozziconacci MJ: A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. Leukemia. 2006 Mar;20(3):536-7. [Article]
  13. Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, Kouzarides T: JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009 Oct 8;461(7265):819-22. doi: 10.1038/nature08448. Epub 2009 Sep 27. [Article]
  14. Yao X, Balamurugan P, Arvey A, Leslie C, Zhang L: Heme controls the regulation of protein tyrosine kinases Jak2 and Src. Biochem Biophys Res Commun. 2010 Dec 3;403(1):30-5. doi: 10.1016/j.bbrc.2010.10.101. Epub 2010 Oct 29. [Article]
  15. Guilluy C, Bregeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G: The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010 Feb;16(2):183-90. doi: 10.1038/nm.2079. Epub 2010 Jan 24. [Article]
  16. Jakel H, Weinl C, Hengst L: Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor signaling to cell cycle control. Oncogene. 2011 Aug 11;30(32):3502-12. doi: 10.1038/onc.2011.68. Epub 2011 Mar 21. [Article]
  17. Wallace TA, Sayeski PP: Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent gene expression? Cell Biochem Biophys. 2006;44(2):213-22. [Article]
  18. Ghoreschi K, Laurence A, O'Shea JJ: Janus kinases in immune cell signaling. Immunol Rev. 2009 Mar;228(1):273-87. doi: 10.1111/j.1600-065X.2008.00754.x. [Article]
  19. Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF, Rossjohn J: The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood. 2006 Jan 1;107(1):176-83. Epub 2005 Sep 20. [Article]
  20. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-61. [Article]
  21. Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, Duffy A, Boyd EM, Bench AJ, Scott MA, Vassiliou GS, Milligan DW, Smith SR, Erber WN, Bareford D, Wilkins BS, Reilly JT, Harrison CN, Green AR: Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet. 2005 Dec 3;366(9501):1945-53. [Article]
  22. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-8. [Article]
  23. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005 Apr 28;352(17):1779-90. [Article]
  24. Chung RT, Iafrate AJ, Amrein PC, Sahani DV, Misdraji J: Case records of the Massachusetts General Hospital. Case 15-2006. A 46-year-old woman with sudden onset of abdominal distention. N Engl J Med. 2006 May 18;354(20):2166-75. [Article]
  25. Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, Min WS, Nam SW, Park WS, Lee JY, Yoo NJ, Lee SH: The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene. 2006 Mar 2;25(9):1434-6. [Article]
  26. Jamieson CH, Gotlib J, Durocher JA, Chao MP, Mariappan MR, Lay M, Jones C, Zehnder JL, Lilleberg SL, Weissman IL: The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6224-9. Epub 2006 Apr 7. [Article]
  27. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, Futreal PA, Erber WN, McMullin MF, Harrison CN, Warren AJ, Gilliland DG, Lodish HF, Green AR: JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007 Feb 1;356(5):459-68. [Article]
  28. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]
  29. Mead AJ, Rugless MJ, Jacobsen SE, Schuh A: Germline JAK2 mutation in a family with hereditary thrombocytosis. N Engl J Med. 2012 Mar 8;366(10):967-9. doi: 10.1056/NEJMc1200349. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05243XL019investigationalunknownDetails
DB047162-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-oneexperimentalunknownDetails
DB071615-phenyl-1H-indazol-3-amineexperimentalunknownDetails
DB071624-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamideexperimentalunknownDetails
DB080674-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUMexperimentalunknownDetails
DB08877RuxolitinibapprovedyesinhibitorDetails
DB08895Tofacitinibapproved, investigationalyesantagonistinhibitorDetails
DB11817Baricitinibapproved, investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB12500Fedratinibapproved, investigationalyesinhibitorDetails
DB11986Entrectinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails
DB15822Pralsetinibapproved, investigationalunknowninhibitorDetails
DB14973Abrocitinibapproved, investigationalunknowninhibitorDetails
DB11697Pacritinibapproved, investigationalyesinhibitorDetails
DB11763Momelotinibapproved, investigationalyesinhibitorDetails