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
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  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. [PubMed:9446644]
  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. [PubMed:9326218]
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  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. [PubMed:19783980]
  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. [PubMed:21036157]
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  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. [PubMed:21423214]
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  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. [PubMed:16325696]
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  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. [PubMed:22397670]

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