ID JAK2_HUMAN Reviewed; 1132 AA. AC O60674; O14636; O75297; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2001, sequence version 2. DT 27-MAR-2024, entry version 241. DE RecName: Full=Tyrosine-protein kinase JAK2 {ECO:0000305}; DE EC=2.7.10.2 {ECO:0000269|PubMed:16174768, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263}; DE AltName: Full=Janus kinase 2; DE Short=JAK-2; GN Name=JAK2 {ECO:0000312|HGNC:HGNC:6192}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9618263; DOI=10.1006/bbrc.1998.8685; RA Saltzman A., Stone M., Franks C., Searfoss G., Munro R., Jaye M., RA Ivashchenko Y.; RT "Cloning and characterization of human Jak-2 kinase: high mRNA expression RT in immune cells and muscle tissue."; RL Biochem. Biophys. Res. Commun. 246:627-633(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9446644; RA Dalal I., Arpaia E., Dadi H., Kulkarni S., Squire J., Roifman C.M.; RT "Cloning and characterization of the human homolog of mouse Jak2."; RL Blood 91:844-851(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND CHROMOSOMAL TRANSLOCATION WITH ETV6. RX PubMed=9326218; RA Peeters P., Raynaud S.D., Cools J., Wlodarska I., Grosgeorge J., Philip P., RA Monpoux F., Van Rompaey L., Baens M., Van Den Berghe H., Marynen P.; RT "Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated RT kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a RT myeloid leukemia."; RL Blood 90:2535-2540(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION WITH IFNGR2, AND RP PHOSPHORYLATION. RX PubMed=7615558; DOI=10.1074/jbc.270.29.17528; RA Sakatsume M., Igarashi K., Winestock K.D., Garotta G., Larner A.C., RA Finbloom D.S.; RT "The Jak kinases differentially associate with the alpha and beta RT (accessory factor) chains of the interferon gamma receptor to form a RT functional receptor unit capable of activating STAT transcription RT factors."; RL J. Biol. Chem. 270:17528-17534(1995). RN [6] RP INTERACTION WITH IFNGR2, AND PHOSPHORYLATION. RX PubMed=7673114; DOI=10.1074/jbc.270.36.20915; RA Kotenko S.V., Izotova L.S., Pollack B.P., Mariano T.M., Donnelly R.J., RA Muthukumaran G., Cook J.R., Garotta G., Silvennoinen O., Ihle J.N.; RT "Interaction between the components of the interferon gamma receptor RT complex."; RL J. Biol. Chem. 270:20915-20921(1995). RN [7] RP INTERACTION WITH SKB1. RX PubMed=10531356; DOI=10.1074/jbc.274.44.31531; RA Pollack B.P., Kotenko S.V., He W., Izotova L.S., Barnoski B.L., Pestka S.; RT "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with RT Jak kinases and contains protein methyltransferase activity."; RL J. Biol. Chem. 274:31531-31542(1999). RN [8] RP INTERACTION WITH STAM2. RC TISSUE=Fetal brain; RX PubMed=10899310; DOI=10.1016/s0014-5793(00)01760-9; RA Endo K., Takeshita T., Kasai H., Sasaki Y., Tanaka N., Asao H., Kikuchi K., RA Yamada M., Chenb M., O'Shea J.J., Sugamura K.; RT "STAM2, a new member of the STAM family, binding to the Janus kinases."; RL FEBS Lett. 477:55-61(2000). RN [9] RP FUNCTION, AND INTERACTION WITH IL23R. RX PubMed=12023369; DOI=10.4049/jimmunol.168.11.5699; RA Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., RA Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., RA O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., RA Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.; RT "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 RT and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [10] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=15805263; DOI=10.1158/0008-5472.can-04-4263; RA Reiter A., Walz C., Watmore A., Schoch C., Blau I., Schlegelberger B., RA Berger U., Telford N., Aruliah S., Yin J.A., Vanstraelen D., Barker H.F., RA Taylor P.C., O'Driscoll A., Benedetti F., Rudolph C., Kolb H.-J., RA Hochhaus A., Hehlmann R., Chase A., Cross N.C.P.; RT "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute RT leukemia that fuses PCM1 to JAK2."; RL Cancer Res. 65:2662-2667(2005). RN [11] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16034466; DOI=10.1038/sj.leu.2403879; RA Murati A., Gelsi-Boyer V., Adelaide J., Perot C., Talmant P., Giraudier S., RA Lode L., Letessier A., Delaval B., Brunel V., Imbert M., Garand R., RA Xerri L., Birnbaum D., Mozziconacci M.-J., Chaffanet M.; RT "PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid RT leukemia with t(8;9) translocation."; RL Leukemia 19:1692-1696(2005). RN [12] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16091753; DOI=10.1038/sj.onc.1208850; RA Bousquet M., Quelen C., De Mas V., Duchayne E., Roquefeuil B., Delsol G., RA Laurent G., Dastugue N., Brousset P.; RT "The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia RT yields a new PCM1-JAK2 fusion gene."; RL Oncogene 24:7248-7252(2005). RN [13] RP CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16769584; RA Bacher U., Reiter A., Haferlach T., Mueller L., Schnittger S., Kern W., RA Schoch C.; RT "A combination of cytomorphology, cytogenetic analysis, fluorescence in RT situ hybridization and reverse transcriptase polymerase chain reaction for RT establishing clonality in cases of persisting hypereosinophilia."; RL Haematologica 91:817-820(2006). RN [14] RP TISSUE SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION WITH PCM1. RX PubMed=16424865; DOI=10.1038/sj.leu.2404104; RA Adelaide J., Perot C., Gelsi-Boyer V., Pautas C., Murati A., RA Copie-Bergman C., Imbert M., Chaffanet M., Birnbaum D., Mozziconacci M.-J.; RT "A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell RT lymphoma."; RL Leukemia 20:536-537(2006). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19783980; DOI=10.1038/nature08448; RA Dawson M.A., Bannister A.J., Gottgens B., Foster S.D., Bartke T., RA Green A.R., Kouzarides T.; RT "JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin."; RL Nature 461:819-822(2009). RN [16] RP ACTIVITY REGULATION. RX PubMed=21036157; DOI=10.1016/j.bbrc.2010.10.101; RA Yao X., Balamurugan P., Arvey A., Leslie C., Zhang L.; RT "Heme controls the regulation of protein tyrosine kinases Jak2 and Src."; RL Biochem. Biophys. Res. Commun. 403:30-35(2010). RN [17] RP INTERACTION WITH HSP90AB1. RX PubMed=20353823; DOI=10.1016/j.cellsig.2010.03.012; RA Cheng M.B., Zhang Y., Zhong X., Sutter B., Cao C.Y., Chen X.S., Cheng X.K., RA Zhang Y., Xiao L., Shen Y.F.; RT "Stat1 mediates an auto-regulation of hsp90beta gene in heat shock RT response."; RL Cell. Signal. 22:1206-1213(2010). RN [18] RP FUNCTION. RX PubMed=20098430; DOI=10.1038/nm.2079; RA Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., RA Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., RA Offermanns S., Pacaud P., Loirand G.; RT "The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on RT vascular tone and blood pressure."; RL Nat. Med. 16:183-190(2010). RN [19] RP FUNCTION IN PHOSPHORYLATION OF CDKN1B. RX PubMed=21423214; DOI=10.1038/onc.2011.68; RA Jakel H., Weinl C., Hengst L.; RT "Phosphorylation of p27Kip1 by JAK2 directly links cytokine receptor RT signaling to cell cycle control."; RL Oncogene 30:3502-3512(2011). RN [20] RP FUNCTION, INTERACTION WITH STRA6, AND PHOSPHORYLATION. RX PubMed=21368206; DOI=10.1073/pnas.1011115108; RA Berry D.C., Jin H., Majumdar A., Noy N.; RT "Signaling by vitamin A and retinol-binding protein regulates gene RT expression to inhibit insulin responses."; RL Proc. Natl. Acad. Sci. U.S.A. 108:4340-4345(2011). RN [21] RP REVIEW ON FUNCTION. RX PubMed=16456223; DOI=10.1385/cbb:44:2:213; RA Wallace T.A., Sayeski P.P.; RT "Jak2 tyrosine kinase: a mediator of both housekeeping and ligand-dependent RT gene expression?"; RL Cell Biochem. Biophys. 44:213-222(2006). RN [22] RP REVIEW ON FUNCTION. RX PubMed=19290934; DOI=10.1111/j.1600-065x.2008.00754.x; RA Ghoreschi K., Laurence A., O'Shea J.J.; RT "Janus kinases in immune cell signaling."; RL Immunol. Rev. 228:273-287(2009). RN [23] RP INTERACTION WITH ASB2, AND PROTEASOMAL DEGRADATION. RX PubMed=21119685; DOI=10.1038/cr.2010.165; RA Nie L., Zhao Y., Wu W., Yang Y.Z., Wang H.C., Sun X.H.; RT "Notch-induced Asb2 expression promotes protein ubiquitination by forming RT non-canonical E3 ligase complexes."; RL Cell Res. 21:754-769(2011). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-570, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP INTERACTION WITH RHEX. RX PubMed=25092874; DOI=10.1084/jem.20130624; RA Verma R., Su S., McCrann D.J., Green J.M., Leu K., Young P.R., Schatz P.J., RA Silva J.C., Stokes M.P., Wojchowski D.M.; RT "RHEX, a novel regulator of human erythroid progenitor cell expansion and RT erythroblast development."; RL J. Exp. Med. 211:1715-1722(2014). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 840-1132 IN COMPLEX WITH SYNTHETIC RP INHIBITOR, CATALYTIC ACTIVITY, IDENTIFICATION BY MASS SPECTROMETRY, AND RP PHOSPHORYLATION AT TYR-1007 AND TYR-1008. RX PubMed=16174768; DOI=10.1182/blood-2005-06-2413; RA Lucet I.S., Fantino E., Styles M., Bamert R., Patel O., Broughton S.E., RA Walter M., Burns C.J., Treutlein H., Wilks A.F., Rossjohn J.; RT "The structural basis of Janus kinase 2 inhibition by a potent and specific RT pan-Janus kinase inhibitor."; RL Blood 107:176-183(2006). RN [27] RP VARIANT PV PHE-617. RX PubMed=15781101; DOI=10.1016/s0140-6736(05)71142-9; RG The cancer genome project; RA Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., RA Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., RA Green A.R.; RT "Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative RT disorders."; RL Lancet 365:1054-1061(2005). RN [28] RP ERRATUM OF PUBMED:15781101. RG The cancer genome project; RA Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., RA Vassiliou G.S., Bench A.J., Boyd E.M., Curtin N., Scott M.A., Erber W.N., RA Green A.R.; RL Lancet 366:122-122(2005). RN [29] RP VARIANT THCYT3 PHE-617. RX PubMed=16325696; DOI=10.1016/s0140-6736(05)67785-9; RG The United Kingdom myeloproliferative disorders study group; RG The medical research council adult leukaemia working party; RG The Australasian leukaemia and lymphoma group; RA Campbell P.J., Scott L.M., Buck G., Wheatley K., East C.L., Marsden J.T., RA Duffy A., Boyd E.M., Bench A.J., Scott M.A., Vassiliou G.S., Milligan D.W., RA Smith S.R., Erber W.N., Bareford D., Wilkins B.S., Reilly J.T., RA Harrison C.N., Green A.R.; RT "Definition of subtypes of essential thrombocythaemia and relation to RT polycythaemia vera based on JAK2 V617F mutation status: a prospective RT study."; RL Lancet 366:1945-1953(2005). RN [30] RP VARIANT PV PHE-617, AND CHARACTERIZATION OF VARIANT PV PHE-617. RX PubMed=15793561; DOI=10.1038/nature03546; RA James C., Ugo V., Le Couedic J.-P., Staerk J., Delhommeau F., Lacout C., RA Garcon L., Raslova H., Berger R., Bennaceur-Griscelli A., Villeval J.L., RA Constantinescu S.N., Casadevall N., Vainchenker W.; RT "A unique clonal JAK2 mutation leading to constitutive signalling causes RT polycythaemia vera."; RL Nature 434:1144-1148(2005). RN [31] RP VARIANT PV PHE-617. RX PubMed=15858187; DOI=10.1056/nejmoa051113; RA Kralovics R., Passamonti F., Buser A.S., Teo S.-S., Tiedt R., Passweg J.R., RA Tichelli A., Cazzola M., Skoda R.C.; RT "A gain-of-function mutation of JAK2 in myeloproliferative disorders."; RL N. Engl. J. Med. 352:1779-1790(2005). RN [32] RP ASSOCIATION OF VARIANT PHE-617 WITH SUSCEPTIBILITY BUDD-CHIARI SYNDROME. RX PubMed=16707754; DOI=10.1056/nejmcpc069006; RA Chung R.T., Iafrate A.J., Amrein P.C., Sahani D.V., Misdraji J.; RT "Case records of the Massachusetts General Hospital. Case 15-2006: a 46- RT year-old woman with sudden onset of abdominal distention."; RL N. Engl. J. Med. 354:2166-2175(2006). RN [33] RP VARIANTS AML ASN-607 AND PHE-617. RX PubMed=16247455; DOI=10.1038/sj.onc.1209163; RA Lee J.W., Kim Y.G., Soung Y.H., Han K.J., Kim S.Y., Rhim H.S., Min W.S., RA Nam S.W., Park W.S., Lee J.Y., Yoo N.J., Lee S.H.; RT "The JAK2 V617F mutation in de novo acute myelogenous leukemias."; RL Oncogene 25:1434-1436(2006). RN [34] RP VARIANT PV PHE-617. RX PubMed=16603627; DOI=10.1073/pnas.0601462103; RA Jamieson C.H.M., Gotlib J., Durocher J.A., Chao M.P., Mariappan M.R., RA Lay M., Jones C., Zehnder J.L., Lilleberg S.L., Weissman I.L.; RT "The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia RT vera and predisposes toward erythroid differentiation."; RL Proc. Natl. Acad. Sci. U.S.A. 103:6224-6229(2006). RN [35] RP VARIANTS MYELOPROLIFERATIVE DISORDER WITH ERYTHROCYTOSIS 537-PHE--LYS-539 RP DELINS LEU; 538-HIS-LYS-539 DELINS GLN-LEU AND LEU-539. RX PubMed=17267906; DOI=10.1056/nejmoa065202; RA Scott L.M., Tong W., Levine R.L., Scott M.A., Beer P.A., Stratton M.R., RA Futreal P.A., Erber W.N., McMullin M.F., Harrison C.N., Warren A.J., RA Gilliland D.G., Lodish H.F., Green A.R.; RT "JAK2 exon 12 mutations in polycythemia vera and idiopathic RT erythrocytosis."; RL N. Engl. J. Med. 356:459-468(2007). RN [36] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-127; GLN-191; ARG-346; GLU-377; VAL-393 RP AND HIS-1063. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [37] RP VARIANT THCYT3 ILE-617. RX PubMed=22397670; DOI=10.1056/nejmc1200349; RA Mead A.J., Rugless M.J., Jacobsen S.E., Schuh A.; RT "Germline JAK2 mutation in a family with hereditary thrombocytosis."; RL N. Engl. J. Med. 366:967-969(2012). CC -!- FUNCTION: Non-receptor tyrosine kinase involved in various processes CC such as cell growth, development, differentiation or histone CC modifications. Mediates essential signaling events in both innate and CC adaptive immunity. In the cytoplasm, plays a pivotal role in signal CC transduction via its association with type I receptors such as growth CC hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), CC thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN- CC beta, IFN-gamma and multiple interleukins (PubMed:7615558). Following CC ligand-binding to cell surface receptors, phosphorylates specific CC tyrosine residues on the cytoplasmic tails of the receptor, creating CC docking sites for STATs proteins (PubMed:9618263). Subsequently, CC phosphorylates the STATs proteins once they are recruited to the CC receptor. Phosphorylated STATs then form homodimer or heterodimers and CC translocate to the nucleus to activate gene transcription. For example, CC cell stimulation with erythropoietin (EPO) during erythropoiesis leads CC to JAK2 autophosphorylation, activation, and its association with CC erythropoietin receptor (EPOR) that becomes phosphorylated in its CC cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, CC phosphorylated and activated by JAK2. Once activated, dimerized STAT5 CC translocates into the nucleus and promotes the transcription of several CC essential genes involved in the modulation of erythropoiesis. Part of a CC signaling cascade that is activated by increased cellular retinol and CC that leads to the activation of STAT5 (STAT5A or STAT5B) CC (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced CC ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle CC by phosphorylating CDKN1B (PubMed:21423214). Cooperates with CC TEC through reciprocal phosphorylation to mediate cytokine-driven CC activation of FOS transcription. In the nucleus, plays a key role in CC chromatin by specifically mediating phosphorylation of 'Tyr-41' of CC histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 CC (HP1 alpha) from chromatin (PubMed:19783980). CC {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:19783980, CC ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, CC ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:7615558, CC ECO:0000269|PubMed:9618263}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305}; CC Note=Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely CC to be the in vivo cofactor. {ECO:0000305|PubMed:7615558}; CC -!- ACTIVITY REGULATION: Regulated by autophosphorylation, can both CC activate or decrease activity (By similarity). Heme regulates its CC activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 CC (PubMed:21036157). {ECO:0000250|UniProtKB:Q62120, CC ECO:0000269|PubMed:21036157}. CC -!- SUBUNIT: Interacts with EPOR, LYN, SIRPA, SH2B1 and TEC (By CC similarity). Interacts with IL23R (PubMed:12023369). Interacts with CC SKB1 (PubMed:10531356). Interacts with STAM2 (PubMed:10899310). CC Interacts with IFNGR2 (via intracellular domain) (PubMed:7673114, CC PubMed:7615558). Interacts with LEPR (Isoform B) (By similarity). CC Interacts with HSP90AB1; promotes functional activation in a heat CC shock-dependent manner (PubMed:20353823). Interacts with STRA6 CC (PubMed:21368206). Interacts with RHEX; this interaction occurs in a CC erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts with CC ASB2; the interaction targets JAK2 for Notch-induced proteasomal CC degradation (PubMed:21119685). {ECO:0000250|UniProtKB:Q62120, CC ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:10899310, CC ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:16174768, CC ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:21119685, CC ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:25092874, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7673114}. CC -!- INTERACTION: CC O60674; P32927: CSF2RB; NbExp=4; IntAct=EBI-518647, EBI-1809771; CC O60674; Q01344: IL5RA; NbExp=2; IntAct=EBI-518647, EBI-1759442; CC O60674; P23458: JAK1; NbExp=4; IntAct=EBI-518647, EBI-1383438; CC O60674; O60674: JAK2; NbExp=7; IntAct=EBI-518647, EBI-518647; CC O60674; P40238: MPL; NbExp=6; IntAct=EBI-518647, EBI-6511486; CC O60674; P16333: NCK1; NbExp=2; IntAct=EBI-518647, EBI-389883; CC O60674; P18031: PTPN1; NbExp=5; IntAct=EBI-518647, EBI-968788; CC O60674; O75116: ROCK2; NbExp=2; IntAct=EBI-518647, EBI-366288; CC O60674; P29597: TYK2; NbExp=2; IntAct=EBI-518647, EBI-1383454; CC O60674; Q9JHI9: Slc40a1; Xeno; NbExp=3; IntAct=EBI-518647, EBI-2931424; CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}. Cytoplasm CC {ECO:0000269|PubMed:19783980}. Nucleus {ECO:0000269|PubMed:19783980}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed throughout most tissues. CC {ECO:0000269|PubMed:16424865}. CC -!- DOMAIN: Possesses 2 protein kinase domains. The second one probably CC contains the catalytic domain, while the presence of slight differences CC suggest a different role for protein kinase 1 (By similarity). CC {ECO:0000250}. CC -!- PTM: Autophosphorylated, leading to regulate its activity. Leptin CC promotes phosphorylation on tyrosine residues, including CC phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr- CC 119 in response to EPO down-regulates its kinase activity (By CC similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in CC response to growth hormone (GH) are required for maximal kinase CC activity (By similarity). Also phosphorylated by TEC (By similarity). CC Phosphorylated on tyrosine residues in response to interferon gamma CC signaling (PubMed:7615558, PubMed:7673114). Phosphorylated on tyrosine CC residues in response to a signaling cascade that is activated by CC increased cellular retinol (PubMed:21368206). CC {ECO:0000250|UniProtKB:Q62120, ECO:0000269|PubMed:21368206, CC ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7673114}. CC -!- PTM: Undergoes Notch-induced ubiquitination and subsequent proteasomal CC degradation which is mediated by ASB1 or ASB2, the substrate- CC recognition components of probable ECS E3 ubiquitin-protein ligase CC complexes. {ECO:0000269|PubMed:21119685}. CC -!- DISEASE: Note=Chromosomal aberrations involving JAK2 are found in both CC chronic and acute forms of eosinophilic, lymphoblastic and myeloid CC leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein CC kinase domain of JAK2 to the major portion of PCM1. Translocation CC t(9;12)(p24;p13) with ETV6. CC -!- DISEASE: Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused CC by obstruction of hepatic venous outflow involving either the hepatic CC veins or the terminal segment of the inferior vena cava. Obstructions CC are generally caused by thrombosis and lead to hepatic congestion and CC ischemic necrosis. Clinical manifestations observed in the majority of CC patients include hepatomegaly, right upper quadrant pain and abdominal CC ascites. Budd-Chiari syndrome is associated with a combination of CC disease states including primary myeloproliferative syndromes and CC thrombophilia due to factor V Leiden, protein C deficiency and CC antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical CC complication in patients with polycythemia vera. CC {ECO:0000269|PubMed:16707754}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative CC disorder characterized by abnormal proliferation of all hematopoietic CC bone marrow elements, erythroid hyperplasia, an absolute increase in CC total blood volume, but also by myeloid leukocytosis, thrombocytosis CC and splenomegaly. {ECO:0000269|PubMed:15781101, CC ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, CC ECO:0000269|PubMed:16603627}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative CC disorder characterized by excessive platelet production, resulting in CC increased numbers of circulating platelets. It can be associated with CC spontaneous hemorrhages and thrombotic episodes. CC {ECO:0000269|PubMed:16325696, ECO:0000269|PubMed:22397670}. Note=The CC disease may be caused by variants affecting the gene represented in CC this entry. CC -!- DISEASE: Myelofibrosis (MYELOF) [MIM:254450]: A disorder characterized CC by replacement of the bone marrow by fibrous tissue, occurring in CC association with a myeloproliferative disorder. Clinical manifestations CC may include anemia, pallor, splenomegaly, hypermetabolic state, CC petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal CC hypertension. Note=The disease is caused by variants affecting the gene CC represented in this entry. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC {ECO:0000269|PubMed:16247455}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. JAK subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/98/JAK"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF058925; AAC23982.1; -; mRNA. DR EMBL; AF001362; AAC23653.1; -; mRNA. DR EMBL; AF005216; AAB82092.1; -; mRNA. DR EMBL; AL161450; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS6457.1; -. DR PIR; JW0091; JW0091. DR RefSeq; NP_001309123.1; NM_001322194.1. DR RefSeq; NP_001309124.1; NM_001322195.1. DR RefSeq; NP_001309125.1; NM_001322196.1. DR RefSeq; NP_001309133.1; NM_001322204.1. DR RefSeq; NP_004963.1; NM_004972.3. DR PDB; 2B7A; X-ray; 2.00 A; A/B=840-1132. DR PDB; 2W1I; X-ray; 2.60 A; A/B=835-1132. DR PDB; 2XA4; X-ray; 2.04 A; A/B=835-1132. DR PDB; 3E62; X-ray; 1.92 A; A=839-1131. DR PDB; 3E63; X-ray; 1.90 A; A=839-1131. DR PDB; 3E64; X-ray; 1.80 A; A=839-1131. DR PDB; 3FUP; X-ray; 2.40 A; A/B=840-1132. DR PDB; 3IO7; X-ray; 2.60 A; A=842-1132. DR PDB; 3IOK; X-ray; 2.10 A; A=842-1132. DR PDB; 3JY9; X-ray; 2.10 A; A=842-1130. DR PDB; 3KCK; X-ray; 2.20 A; A=842-1132. DR PDB; 3KRR; X-ray; 1.80 A; A=840-1132. DR PDB; 3LPB; X-ray; 2.00 A; A/B=840-1132. DR PDB; 3Q32; X-ray; 2.50 A; A/B=839-1132. DR PDB; 3RVG; X-ray; 2.50 A; A=835-1132. DR PDB; 3TJC; X-ray; 2.40 A; A/B=837-1132. DR PDB; 3TJD; X-ray; 2.90 A; A/B=837-1132. DR PDB; 3UGC; X-ray; 1.34 A; A=840-1132. DR PDB; 3ZMM; X-ray; 2.51 A; A/B=835-1132. DR PDB; 4AQC; X-ray; 1.90 A; A/B=835-1132. DR PDB; 4BBE; X-ray; 1.90 A; A/B/C/D=839-1132. DR PDB; 4BBF; X-ray; 2.00 A; A/B/C/D=839-1132. DR PDB; 4C61; X-ray; 2.45 A; A/B=835-1132. DR PDB; 4C62; X-ray; 2.75 A; A/B=835-1132. DR PDB; 4D0W; X-ray; 1.77 A; A=835-1132. DR PDB; 4D0X; X-ray; 1.82 A; A=835-1132. DR PDB; 4D1S; X-ray; 1.66 A; A=835-1132. DR PDB; 4E4M; X-ray; 2.25 A; A/B/D/E=833-1132. DR PDB; 4E6D; X-ray; 2.22 A; A/B=835-1132. DR PDB; 4E6Q; X-ray; 1.95 A; A/B=835-1132. DR PDB; 4F08; X-ray; 2.82 A; A/B=833-1132. DR PDB; 4F09; X-ray; 2.40 A; A=833-1132. DR PDB; 4FVP; X-ray; 2.01 A; A=536-812. DR PDB; 4FVQ; X-ray; 1.75 A; A=536-812. DR PDB; 4FVR; X-ray; 2.00 A; A=536-812. DR PDB; 4GFM; X-ray; 2.30 A; A=833-1132. DR PDB; 4GMY; X-ray; 2.40 A; A=833-1132. DR PDB; 4HGE; X-ray; 2.30 A; A/B=833-1132. DR PDB; 4IVA; X-ray; 1.50 A; A=833-1132. DR PDB; 4JI9; X-ray; 2.40 A; A/B=833-1132. DR PDB; 4JIA; X-ray; 1.85 A; A=833-1132. DR PDB; 4P7E; X-ray; 2.40 A; A/B=840-1132. DR PDB; 4YTC; X-ray; 2.16 A; A=842-1132. DR PDB; 4YTF; X-ray; 1.78 A; A=842-1132. DR PDB; 4YTH; X-ray; 2.04 A; A=842-1132. DR PDB; 4YTI; X-ray; 2.52 A; A=842-1132. DR PDB; 4Z32; X-ray; 3.04 A; A/B/C/D/E/F/G/H=31-516. DR PDB; 4ZIM; X-ray; 2.65 A; A/B=839-1132. DR PDB; 5AEP; X-ray; 1.95 A; A=835-1132. DR PDB; 5CF4; X-ray; 2.38 A; A/B=839-1132. DR PDB; 5CF5; X-ray; 2.45 A; A/B=839-1132. DR PDB; 5CF6; X-ray; 2.50 A; A/B=839-1132. DR PDB; 5CF8; X-ray; 1.80 A; A/B=839-1132. DR PDB; 5HEZ; X-ray; 2.66 A; A/B/C/D=833-1132. DR PDB; 5I4N; X-ray; 1.54 A; A=535-812. DR PDB; 5L3A; X-ray; 1.98 A; A=840-1132. DR PDB; 5TQ3; X-ray; 2.69 A; A/B=837-1132. DR PDB; 5TQ4; X-ray; 2.30 A; A=837-1132. DR PDB; 5TQ5; X-ray; 2.30 A; A=837-1132. DR PDB; 5TQ6; X-ray; 2.06 A; A/B=837-1132. DR PDB; 5TQ7; X-ray; 2.10 A; A/B=837-1132. DR PDB; 5TQ8; X-ray; 1.59 A; A=837-1132. DR PDB; 5USY; X-ray; 2.00 A; A/B=840-1132. DR PDB; 5USZ; X-ray; 2.10 A; A=536-812. DR PDB; 5UT0; X-ray; 2.10 A; A=536-812. DR PDB; 5UT1; X-ray; 1.95 A; A=536-812. DR PDB; 5UT2; X-ray; 1.75 A; A=536-812. DR PDB; 5UT3; X-ray; 1.50 A; A=536-812. DR PDB; 5UT4; X-ray; 2.00 A; A=536-812. DR PDB; 5UT5; X-ray; 1.90 A; A=536-812. DR PDB; 5UT6; X-ray; 1.65 A; A=536-812. DR PDB; 5WEV; X-ray; 1.85 A; A=833-1132. DR PDB; 5WIJ; X-ray; 2.04 A; A=536-812. DR PDB; 5WIK; X-ray; 2.60 A; B=536-812. DR PDB; 5WIL; X-ray; 2.20 A; A=536-812. DR PDB; 5WIM; X-ray; 2.55 A; A=536-812. DR PDB; 5WIN; X-ray; 2.38 A; A=536-812. DR PDB; 6AAJ; X-ray; 2.37 A; A/B=834-1132. DR PDB; 6BBV; X-ray; 1.80 A; A=837-1132. DR PDB; 6BRW; X-ray; 2.03 A; A=536-812. DR PDB; 6BS0; X-ray; 1.54 A; A=536-812. DR PDB; 6BSS; X-ray; 2.10 A; A=536-812. DR PDB; 6D2I; X-ray; 3.19 A; A/B=536-808. DR PDB; 6DRW; X-ray; 2.30 A; A=840-1132. DR PDB; 6E2P; X-ray; 2.83 A; A/B=36-514. DR PDB; 6E2Q; X-ray; 2.65 A; A/B/C/D=36-514. DR PDB; 6G3C; X-ray; 1.60 A; A/B=537-808. DR PDB; 6M9H; X-ray; 1.79 A; A=536-812. DR PDB; 6OAV; X-ray; 1.94 A; A=536-812. DR PDB; 6OBB; X-ray; 1.90 A; A=536-812. DR PDB; 6OBF; X-ray; 1.71 A; A=536-812. DR PDB; 6OBL; X-ray; 2.06 A; A=536-812. DR PDB; 6OCC; X-ray; 2.03 A; A=536-812. DR PDB; 6TPD; X-ray; 1.99 A; A=842-1130. DR PDB; 6VGL; X-ray; 1.90 A; A/B/C/D=840-1132. DR PDB; 6VN8; X-ray; 1.90 A; A/B=840-1132. DR PDB; 6VNB; X-ray; 2.19 A; A/B=840-1132. DR PDB; 6VNC; X-ray; 2.30 A; A/B=840-1132. DR PDB; 6VNE; X-ray; 2.32 A; A/B=840-1132. DR PDB; 6VNF; X-ray; 2.06 A; A/B=840-1132. DR PDB; 6VNG; X-ray; 2.50 A; A/B=840-1132. DR PDB; 6VNH; X-ray; 2.40 A; A/B=840-1132. DR PDB; 6VNI; X-ray; 2.10 A; A/B=840-1132. DR PDB; 6VNJ; X-ray; 1.90 A; A/B=840-1132. DR PDB; 6VNK; X-ray; 2.00 A; A/B/C/D=840-1132. DR PDB; 6VNL; X-ray; 2.40 A; A/B/C/D=840-1132. DR PDB; 6VNM; X-ray; 2.20 A; A/B=840-1132. DR PDB; 6VS3; X-ray; 2.00 A; A/B=840-1132. DR PDB; 6VSN; X-ray; 2.50 A; A/B/C/D=840-1132. DR PDB; 6WTN; X-ray; 1.83 A; A=835-1132. DR PDB; 6WTO; X-ray; 1.74 A; A=835-1132. DR PDB; 6WTP; X-ray; 2.50 A; A=835-1132. DR PDB; 6WTQ; X-ray; 1.80 A; A=835-1132. DR PDB; 6X8E; X-ray; 1.75 A; A/B=837-1132. DR PDB; 6XJK; X-ray; 2.02 A; A=536-812. DR PDB; 7F7W; X-ray; 1.83 A; A/B=536-810. DR PDB; 7JYO; X-ray; 2.16 A; A=536-812. DR PDB; 7JYQ; X-ray; 1.86 A; A=536-812. DR PDB; 7LL4; X-ray; 1.31 A; A=839-1132. DR PDB; 7LL5; X-ray; 1.50 A; A=840-1132. DR PDB; 7Q7I; X-ray; 1.78 A; A=839-1132. DR PDB; 7Q7K; X-ray; 1.61 A; A=839-1132. DR PDB; 7Q7L; X-ray; 1.97 A; A=839-1132. DR PDB; 7Q7W; X-ray; 1.85 A; A=839-1132. DR PDB; 7REE; X-ray; 1.38 A; A=839-1132. DR PDB; 7RN6; X-ray; 1.50 A; A=839-1132. DR PDB; 7T0P; X-ray; 2.04 A; A/B=536-812. DR PDB; 7T1T; X-ray; 2.08 A; A=536-812. DR PDB; 7TEU; X-ray; 1.45 A; A=837-1132. DR PDB; 7UYW; X-ray; 2.51 A; A=842-1132. DR PDB; 8B8N; X-ray; 2.00 A; A=536-812. DR PDB; 8B8U; X-ray; 1.50 A; A/B=536-812. DR PDB; 8B99; X-ray; 1.60 A; A=536-812. DR PDB; 8B9E; X-ray; 1.50 A; A=536-812. DR PDB; 8B9H; X-ray; 1.50 A; A=536-812. DR PDB; 8BA2; X-ray; 1.50 A; A=536-812. DR PDB; 8BA3; X-ray; 1.40 A; A=536-812. DR PDB; 8BA4; X-ray; 2.10 A; A/B=536-812. DR PDB; 8BAB; X-ray; 1.55 A; A=536-812. DR PDB; 8BAK; X-ray; 1.65 A; A=536-812. DR PDB; 8BM2; X-ray; 1.50 A; A/B=840-1132. DR PDB; 8BPV; X-ray; 1.70 A; A=840-1132. DR PDB; 8BPW; X-ray; 1.80 A; A/B=840-1132. DR PDB; 8CZ9; X-ray; 1.65 A; C=811-818. DR PDB; 8EX0; X-ray; 1.85 A; A=536-812. DR PDB; 8EX1; X-ray; 1.50 A; A=536-812. DR PDB; 8EX2; X-ray; 1.90 A; A=536-812. DR PDB; 8EXK; X-ray; 2.10 A; B=1000-1015. DR PDB; 8EYA; X-ray; 2.10 A; D/E=1000-1015. DR PDB; 8EYB; X-ray; 2.35 A; D/E=1000-1015. DR PDB; 8F88; X-ray; 3.10 A; E/F/G=1000-1015. DR PDB; 8G6Z; X-ray; 2.45 A; A/B=837-1132. DR PDB; 8G8O; X-ray; 2.20 A; A/B=837-1132. DR PDB; 8G8X; X-ray; 1.97 A; A/B=837-1132. DR PDBsum; 2B7A; -. DR PDBsum; 2W1I; -. DR PDBsum; 2XA4; -. DR PDBsum; 3E62; -. DR PDBsum; 3E63; -. DR PDBsum; 3E64; -. DR PDBsum; 3FUP; -. DR PDBsum; 3IO7; -. DR PDBsum; 3IOK; -. DR PDBsum; 3JY9; -. DR PDBsum; 3KCK; -. DR PDBsum; 3KRR; -. DR PDBsum; 3LPB; -. DR PDBsum; 3Q32; -. DR PDBsum; 3RVG; -. DR PDBsum; 3TJC; -. DR PDBsum; 3TJD; -. DR PDBsum; 3UGC; -. DR PDBsum; 3ZMM; -. DR PDBsum; 4AQC; -. DR PDBsum; 4BBE; -. DR PDBsum; 4BBF; -. DR PDBsum; 4C61; -. DR PDBsum; 4C62; -. DR PDBsum; 4D0W; -. DR PDBsum; 4D0X; -. DR PDBsum; 4D1S; -. DR PDBsum; 4E4M; -. DR PDBsum; 4E6D; -. DR PDBsum; 4E6Q; -. DR PDBsum; 4F08; -. DR PDBsum; 4F09; -. DR PDBsum; 4FVP; -. DR PDBsum; 4FVQ; -. DR PDBsum; 4FVR; -. DR PDBsum; 4GFM; -. DR PDBsum; 4GMY; -. DR PDBsum; 4HGE; -. DR PDBsum; 4IVA; -. DR PDBsum; 4JI9; -. DR PDBsum; 4JIA; -. DR PDBsum; 4P7E; -. DR PDBsum; 4YTC; -. DR PDBsum; 4YTF; -. DR PDBsum; 4YTH; -. DR PDBsum; 4YTI; -. DR PDBsum; 4Z32; -. DR PDBsum; 4ZIM; -. DR PDBsum; 5AEP; -. DR PDBsum; 5CF4; -. DR PDBsum; 5CF5; -. DR PDBsum; 5CF6; -. DR PDBsum; 5CF8; -. DR PDBsum; 5HEZ; -. DR PDBsum; 5I4N; -. DR PDBsum; 5L3A; -. DR PDBsum; 5TQ3; -. DR PDBsum; 5TQ4; -. DR PDBsum; 5TQ5; -. DR PDBsum; 5TQ6; -. DR PDBsum; 5TQ7; -. DR PDBsum; 5TQ8; -. DR PDBsum; 5USY; -. DR PDBsum; 5USZ; -. DR PDBsum; 5UT0; -. DR PDBsum; 5UT1; -. DR PDBsum; 5UT2; -. DR PDBsum; 5UT3; -. DR PDBsum; 5UT4; -. DR PDBsum; 5UT5; -. DR PDBsum; 5UT6; -. DR PDBsum; 5WEV; -. DR PDBsum; 5WIJ; -. DR PDBsum; 5WIK; -. DR PDBsum; 5WIL; -. DR PDBsum; 5WIM; -. DR PDBsum; 5WIN; -. DR PDBsum; 6AAJ; -. DR PDBsum; 6BBV; -. DR PDBsum; 6BRW; -. DR PDBsum; 6BS0; -. DR PDBsum; 6BSS; -. DR PDBsum; 6D2I; -. DR PDBsum; 6DRW; -. DR PDBsum; 6E2P; -. DR PDBsum; 6E2Q; -. DR PDBsum; 6G3C; -. DR PDBsum; 6M9H; -. DR PDBsum; 6OAV; -. DR PDBsum; 6OBB; -. DR PDBsum; 6OBF; -. DR PDBsum; 6OBL; -. DR PDBsum; 6OCC; -. DR PDBsum; 6TPD; -. DR PDBsum; 6VGL; -. DR PDBsum; 6VN8; -. DR PDBsum; 6VNB; -. DR PDBsum; 6VNC; -. DR PDBsum; 6VNE; -. DR PDBsum; 6VNF; -. DR PDBsum; 6VNG; -. DR PDBsum; 6VNH; -. DR PDBsum; 6VNI; -. DR PDBsum; 6VNJ; -. DR PDBsum; 6VNK; -. DR PDBsum; 6VNL; -. DR PDBsum; 6VNM; -. DR PDBsum; 6VS3; -. DR PDBsum; 6VSN; -. DR PDBsum; 6WTN; -. DR PDBsum; 6WTO; -. DR PDBsum; 6WTP; -. DR PDBsum; 6WTQ; -. DR PDBsum; 6X8E; -. DR PDBsum; 6XJK; -. DR PDBsum; 7F7W; -. DR PDBsum; 7JYO; -. DR PDBsum; 7JYQ; -. DR PDBsum; 7LL4; -. DR PDBsum; 7LL5; -. DR PDBsum; 7Q7I; -. DR PDBsum; 7Q7K; -. DR PDBsum; 7Q7L; -. DR PDBsum; 7Q7W; -. DR PDBsum; 7REE; -. DR PDBsum; 7RN6; -. DR PDBsum; 7T0P; -. DR PDBsum; 7T1T; -. DR PDBsum; 7TEU; -. DR PDBsum; 7UYW; -. DR PDBsum; 8B8N; -. DR PDBsum; 8B8U; -. DR PDBsum; 8B99; -. DR PDBsum; 8B9E; -. DR PDBsum; 8B9H; -. DR PDBsum; 8BA2; -. DR PDBsum; 8BA3; -. DR PDBsum; 8BA4; -. DR PDBsum; 8BAB; -. DR PDBsum; 8BAK; -. DR PDBsum; 8BM2; -. DR PDBsum; 8BPV; -. DR PDBsum; 8BPW; -. DR PDBsum; 8CZ9; -. DR PDBsum; 8EX0; -. DR PDBsum; 8EX1; -. DR PDBsum; 8EX2; -. DR PDBsum; 8EXK; -. DR PDBsum; 8EYA; -. DR PDBsum; 8EYB; -. DR PDBsum; 8F88; -. DR PDBsum; 8G6Z; -. DR PDBsum; 8G8O; -. DR PDBsum; 8G8X; -. DR AlphaFoldDB; O60674; -. DR SMR; O60674; -. DR BioGRID; 109920; 157. DR ComplexPortal; CPX-382; Interleukin-12-receptor complex. DR ComplexPortal; CPX-383; Interleukin-23-receptor complex. DR ComplexPortal; CPX-512; Granulocyte-macrophage colony-stimulating factor-receptor complex. DR ComplexPortal; CPX-6015; Interferon gamma receptor-ligand complex. DR CORUM; O60674; -. DR DIP; DIP-33880N; -. DR IntAct; O60674; 44. DR MINT; O60674; -. DR STRING; 9606.ENSP00000371067; -. DR BindingDB; O60674; -. DR ChEMBL; CHEMBL2971; -. DR DrugBank; DB04716; 2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one. DR DrugBank; DB07162; 4-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamide. DR DrugBank; DB08067; 4-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUM. DR DrugBank; DB07161; 5-phenyl-1H-indazol-3-amine. DR DrugBank; DB14973; Abrocitinib. DR DrugBank; DB11817; Baricitinib. DR DrugBank; DB11986; Entrectinib. DR DrugBank; DB12500; Fedratinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB11697; Pacritinib. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB08877; Ruxolitinib. DR DrugBank; DB08895; Tofacitinib. DR DrugBank; DB05243; XL019. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; O60674; -. DR GuidetoPHARMACOLOGY; 2048; -. DR GlyGen; O60674; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O60674; -. DR PhosphoSitePlus; O60674; -. DR BioMuta; JAK2; -. DR CPTAC; CPTAC-1252; -. DR CPTAC; CPTAC-3095; -. DR CPTAC; CPTAC-3096; -. DR EPD; O60674; -. DR jPOST; O60674; -. DR MassIVE; O60674; -. DR MaxQB; O60674; -. DR PaxDb; 9606-ENSP00000371067; -. DR PeptideAtlas; O60674; -. DR ProteomicsDB; 49519; -. DR Pumba; O60674; -. DR Antibodypedia; 24086; 1575 antibodies from 48 providers. DR DNASU; 3717; -. DR Ensembl; ENST00000381652.4; ENSP00000371067.4; ENSG00000096968.14. DR GeneID; 3717; -. DR KEGG; hsa:3717; -. DR MANE-Select; ENST00000381652.4; ENSP00000371067.4; NM_004972.4; NP_004963.1. DR UCSC; uc003ziw.3; human. DR AGR; HGNC:6192; -. DR CTD; 3717; -. DR DisGeNET; 3717; -. DR GeneCards; JAK2; -. DR HGNC; HGNC:6192; JAK2. DR HPA; ENSG00000096968; Low tissue specificity. DR MalaCards; JAK2; -. DR MIM; 147796; gene. DR MIM; 254450; phenotype. DR MIM; 263300; phenotype. DR MIM; 600880; phenotype. DR MIM; 601626; phenotype. DR MIM; 614521; phenotype. DR neXtProt; NX_O60674; -. DR OpenTargets; ENSG00000096968; -. DR Orphanet; 131; Budd-Chiari syndrome. DR Orphanet; 3318; Essential thrombocythemia. DR Orphanet; 71493; Familial thrombocytosis. DR Orphanet; 729; Polycythemia vera. DR Orphanet; 824; Primary myelofibrosis. DR PharmGKB; PA29989; -. DR VEuPathDB; HostDB:ENSG00000096968; -. DR eggNOG; KOG0197; Eukaryota. DR GeneTree; ENSGT00940000155640; -. DR HOGENOM; CLU_008155_1_0_1; -. DR InParanoid; O60674; -. DR OMA; FMKLHEN; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; O60674; -. DR TreeFam; TF327041; -. DR BRENDA; 2.7.10.2; 2681. DR PathwayCommons; O60674; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation. DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-2586552; Signaling by Leptin. DR Reactome; R-HSA-3214858; RMTs methylate histone arginines. DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. DR Reactome; R-HSA-5673000; RAF activation. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions. DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-877312; Regulation of IFNG signaling. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-9006335; Signaling by Erythropoietin. DR Reactome; R-HSA-9020591; Interleukin-12 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K). DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG). DR Reactome; R-HSA-9027283; Erythropoietin activates STAT5. DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling. DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants. DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-9732724; IFNG signaling activates MAPKs. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; O60674; -. DR SIGNOR; O60674; -. DR BioGRID-ORCS; 3717; 30 hits in 1210 CRISPR screens. DR ChiTaRS; JAK2; human. DR EvolutionaryTrace; O60674; -. DR GeneWiki; Janus_kinase_2; -. DR GenomeRNAi; 3717; -. DR Pharos; O60674; Tclin. DR PRO; PR:O60674; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O60674; Protein. DR Bgee; ENSG00000096968; Expressed in calcaneal tendon and 184 other cell types or tissues. DR ExpressionAtlas; O60674; baseline and differential. DR GO; GO:0005901; C:caveola; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005856; C:cytoskeleton; IEA:InterPro. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0031904; C:endosome lumen; TAS:Reactome. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProt. DR GO; GO:0005925; C:focal adhesion; IDA:HPA. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030526; C:granulocyte macrophage colony-stimulating factor receptor complex; IDA:ComplexPortal. DR GO; GO:0042022; C:interleukin-12 receptor complex; NAS:ComplexPortal. DR GO; GO:0072536; C:interleukin-23 receptor complex; NAS:ComplexPortal. DR GO; GO:0045121; C:membrane raft; ISS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0033130; F:acetylcholine receptor binding; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005131; F:growth hormone receptor binding; ISS:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0035401; F:histone H3Y41 kinase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:Ensembl. DR GO; GO:0005143; F:interleukin-12 receptor binding; ISS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central. DR GO; GO:0051428; F:peptide hormone receptor binding; IEA:Ensembl. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IEA:Ensembl. DR GO; GO:0004672; F:protein kinase activity; NAS:ProtInc. DR GO; GO:0019901; F:protein kinase binding; IDA:BHF-UCL. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:CACAO. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IEA:Ensembl. DR GO; GO:0030041; P:actin filament polymerization; NAS:BHF-UCL. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:BHF-UCL. DR GO; GO:0097296; P:activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0042976; P:activation of Janus kinase activity; ISS:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0006915; P:apoptotic process; ISS:BHF-UCL. DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; ISS:BHF-UCL. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl. DR GO; GO:0036016; P:cellular response to interleukin-3; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal. DR GO; GO:0038065; P:collagen-activated signaling pathway; IMP:ARUK-UCL. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISS:BHF-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0038157; P:granulocyte-macrophage colony-stimulating factor signaling pathway; IDA:ComplexPortal. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; ISS:UniProtKB. DR GO; GO:0006955; P:immune response; NAS:ComplexPortal. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; IDA:UniProt. DR GO; GO:0070757; P:interleukin-35-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038043; P:interleukin-5-mediated signaling pathway; IDA:UniProt. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; TAS:Reactome. DR GO; GO:0035556; P:intracellular signal transduction; ISS:BHF-UCL. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl. DR GO; GO:0061180; P:mammary gland epithelium development; ISS:BHF-UCL. DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc. DR GO; GO:0001774; P:microglial cell activation; ISS:ARUK-UCL. DR GO; GO:0031959; P:mineralocorticoid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:BHF-UCL. DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IEA:Ensembl. DR GO; GO:0043392; P:negative regulation of DNA binding; ISS:BHF-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:BHF-UCL. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:BHF-UCL. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; IEA:Ensembl. DR GO; GO:1902728; P:positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; IEA:Ensembl. DR GO; GO:0060399; P:positive regulation of growth hormone receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:ARUK-UCL. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; NAS:ComplexPortal. DR GO; GO:0070665; P:positive regulation of leukocyte proliferation; IDA:ComplexPortal. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl. DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:ARUK-UCL. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:ComplexPortal. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:ARUK-UCL. DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:ComplexPortal. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:BHF-UCL. DR GO; GO:0010572; P:positive regulation of platelet activation; IDA:ARUK-UCL. DR GO; GO:1901731; P:positive regulation of platelet aggregation; IDA:ARUK-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:ComplexPortal. DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISS:ARUK-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IGI:MGI. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:ComplexPortal. DR GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; NAS:ComplexPortal. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:ComplexPortal. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0035166; P:post-embryonic hemopoiesis; IEA:Ensembl. DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB. DR GO; GO:0034050; P:programmed cell death induced by symbiont; IEA:Ensembl. DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:ARUK-UCL. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0050727; P:regulation of inflammatory response; IDA:BHF-UCL. DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL. DR GO; GO:1905539; P:regulation of postsynapse to nucleus signaling pathway; IEA:Ensembl. DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; ISS:BHF-UCL. DR GO; GO:0014075; P:response to amine; IEA:Ensembl. DR GO; GO:0046677; P:response to antibiotic; IDA:MGI. DR GO; GO:0033194; P:response to hydroperoxide; IEA:Ensembl. DR GO; GO:0070671; P:response to interleukin-12; IDA:BHF-UCL. DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:BHF-UCL. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR GO; GO:0007165; P:signal transduction; ISS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; TAS:Reactome. DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; ISS:BHF-UCL. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13333; FERM_C_JAK2; 1. DR CDD; cd05078; PTK_Jak2_rpt1; 1. DR CDD; cd14205; PTKc_Jak2_rpt2; 1. DR CDD; cd10379; SH2_Jak2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR041155; FERM_F1. DR InterPro; IPR041046; FERM_F2. DR InterPro; IPR041381; JAK1-3/TYK2_PHL_dom. DR InterPro; IPR037838; JAK2_FERM_C-lobe. DR InterPro; IPR035860; JAK2_SH2. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR035588; PTK_Jak2_rpt1. DR InterPro; IPR035589; PTKc_Jak2_rpt2. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016251; Tyr_kinase_non-rcpt_Jak/Tyk2. DR InterPro; IPR020693; Tyr_kinase_non-rcpt_Jak2. DR PANTHER; PTHR45807; TYROSINE-PROTEIN KINASE HOPSCOTCH; 1. DR PANTHER; PTHR45807:SF1; TYROSINE-PROTEIN KINASE JAK2; 1. DR Pfam; PF18379; FERM_F1; 1. DR Pfam; PF18377; FERM_F2; 1. DR Pfam; PF17887; Jak1_Phl; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 2. DR Pfam; PF00017; SH2; 1. DR PIRSF; PIRSF000636; TyrPK_Jak; 1. DR PRINTS; PR01823; JANUSKINASE. DR PRINTS; PR01825; JANUSKINASE2. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00295; B41; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00219; TyrKc; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50057; FERM_3; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; O60674; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; ATP-binding; Chromatin regulator; KW Chromosomal rearrangement; Cytoplasm; Disease variant; Immunity; KW Innate immunity; Kinase; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; KW Reference proteome; Repeat; SH2 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1..1132 FT /note="Tyrosine-protein kinase JAK2" FT /id="PRO_0000088112" FT DOMAIN 37..380 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT DOMAIN 401..482 FT /note="SH2; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 545..809 FT /note="Protein kinase 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 849..1124 FT /note="Protein kinase 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..239 FT /note="Interaction with cytokine/interferon/growth hormone FT receptors" FT /evidence="ECO:0000250" FT ACT_SITE 976 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 855..863 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 882 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 352..353 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 442..443 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 450..451 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 504..505 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT SITE 710..711 FT /note="Breakpoint for translocation to form PCM1-JAK2 FT fusion protein" FT MOD_RES 119 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 372 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 373 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 523 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 570 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 813 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 868 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 966 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 972 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q62120" FT MOD_RES 1007 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:16174768" FT MOD_RES 1008 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:16174768" FT VARIANT 127 FT /note="G -> D (in dbSNP:rs56118985)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041716" FT VARIANT 191 FT /note="K -> Q (in an ovarian serous carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041717" FT VARIANT 346 FT /note="K -> R (in dbSNP:rs55667734)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041718" FT VARIANT 377 FT /note="A -> E (in dbSNP:rs55953208)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041719" FT VARIANT 393 FT /note="L -> V (in dbSNP:rs2230723)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041720" FT VARIANT 537..539 FT /note="FHK -> L (in myeloproliferative disorder with FT erythrocytosis)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032693" FT VARIANT 538..539 FT /note="HK -> QL (in myeloproliferative disorder with FT erythrocytosis)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032694" FT VARIANT 539 FT /note="K -> L (in myeloproliferative disorder with FT erythrocytosis; requires 2 nucleotide substitutions; FT dbSNP:rs121912473)" FT /evidence="ECO:0000269|PubMed:17267906" FT /id="VAR_032695" FT VARIANT 584 FT /note="D -> E (in dbSNP:rs17490221)" FT /id="VAR_043129" FT VARIANT 607 FT /note="K -> N (in AML; dbSNP:rs121912472)" FT /evidence="ECO:0000269|PubMed:16247455" FT /id="VAR_032696" FT VARIANT 617 FT /note="V -> F (in PV, THCYT3 and AML; risk factor for FT Budd-Chiari syndrome; somatic mutation in a high percentage FT of patients with essential thrombocythemia or FT myelofibrosis; leads to constitutive tyrosine FT phosphorylation activity that promotes cytokine FT hypersensitivity; dbSNP:rs77375493)" FT /evidence="ECO:0000269|PubMed:15781101, FT ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, FT ECO:0000269|PubMed:16247455, ECO:0000269|PubMed:16325696, FT ECO:0000269|PubMed:16603627" FT /id="VAR_032697" FT VARIANT 617 FT /note="V -> I (in THCYT3; dbSNP:rs77375493)" FT /evidence="ECO:0000269|PubMed:22397670" FT /id="VAR_067534" FT VARIANT 1063 FT /note="R -> H (in dbSNP:rs41316003)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041721" FT CONFLICT 321 FT /note="P -> S (in Ref. 1; AAC23982)" FT /evidence="ECO:0000305" FT CONFLICT 1126 FT /note="I -> V (in Ref. 2; AAC23653)" FT /evidence="ECO:0000305" FT STRAND 38..45 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 47..49 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 50..55 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 59..63 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 64..75 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 79..81 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 82..84 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 85..89 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 101..104 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 109..116 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 123..125 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 136..139 FT /evidence="ECO:0007829|PDB:4Z32" FT HELIX 147..162 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 172..193 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 197..203 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 206..209 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 212..219 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 223..240 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 247..261 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 263..266 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 268..273 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 285..291 FT /evidence="ECO:0007829|PDB:6E2Q" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 295..301 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 311..313 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 320..322 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 323..330 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 340..349 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 352..358 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 359..376 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 390..398 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 406..415 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 422..427 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 434..443 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 446..456 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 471..473 FT /evidence="ECO:0007829|PDB:6E2Q" FT HELIX 474..481 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 485..488 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 491..494 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 510..513 FT /evidence="ECO:0007829|PDB:6E2Q" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:5WIJ" FT HELIX 542..544 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 545..554 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 557..567 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 569..571 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 573..583 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 585..590 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 591..603 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 612..618 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 621..627 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 634..640 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 642..644 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 647..666 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 676..678 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 679..683 FT /evidence="ECO:0007829|PDB:8EX1" FT TURN 687..690 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 694..697 FT /evidence="ECO:0007829|PDB:8EX1" FT TURN 704..706 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 709..714 FT /evidence="ECO:0007829|PDB:8EX1" FT TURN 715..718 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 721..725 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 727..729 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 732..746 FT /evidence="ECO:0007829|PDB:8EX1" FT TURN 747..750 FT /evidence="ECO:0007829|PDB:8EX1" FT TURN 753..756 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 759..767 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 778..780 FT /evidence="ECO:0007829|PDB:5I4N" FT HELIX 781..787 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 792..794 FT /evidence="ECO:0007829|PDB:8EX1" FT HELIX 798..807 FT /evidence="ECO:0007829|PDB:8EX1" FT STRAND 836..838 FT /evidence="ECO:0007829|PDB:4E4M" FT TURN 841..843 FT /evidence="ECO:0007829|PDB:6DRW" FT HELIX 846..848 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 849..857 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 859..868 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 872..874 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 877..886 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 889..903 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 913..917 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 919..922 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 926..930 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 937..944 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 945..947 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 950..969 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 979..981 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 982..986 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 989..992 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 995..997 FT /evidence="ECO:0007829|PDB:7Q7K" FT STRAND 1006..1009 FT /evidence="ECO:0007829|PDB:4IVA" FT HELIX 1018..1020 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 1023..1028 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 1030..1032 FT /evidence="ECO:0007829|PDB:4IVA" FT HELIX 1033..1048 FT /evidence="ECO:0007829|PDB:7LL4" FT TURN 1049..1051 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 1053..1055 FT /evidence="ECO:0007829|PDB:4IVA" FT HELIX 1057..1065 FT /evidence="ECO:0007829|PDB:7LL4" FT STRAND 1069..1071 FT /evidence="ECO:0007829|PDB:5HEZ" FT HELIX 1072..1083 FT /evidence="ECO:0007829|PDB:7LL4" FT TURN 1084..1086 FT /evidence="ECO:0007829|PDB:5HEZ" FT HELIX 1096..1105 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 1110..1112 FT /evidence="ECO:0007829|PDB:7LL4" FT HELIX 1116..1129 FT /evidence="ECO:0007829|PDB:7LL4" SQ SEQUENCE 1132 AA; 130674 MW; C30669EF1A7DA80C CRC64; MGMACLTMTE MEGTSTSSIY QNGDISGNAN SMKQIDPVLQ VYLYHSLGKS EADYLTFPSG EYVAEEICIA ASKACGITPV YHNMFALMSE TERIWYPPNH VFHIDESTRH NVLYRIRFYF PRWYCSGSNR AYRHGISRGA EAPLLDDFVM SYLFAQWRHD FVHGWIKVPV THETQEECLG MAVLDMMRIA KENDQTPLAI YNSISYKTFL PKCIRAKIQD YHILTRKRIR YRFRRFIQQF SQCKATARNL KLKYLINLET LQSAFYTEKF EVKEPGSGPS GEEIFATIII TGNGGIQWSR GKHKESETLT EQDLQLYCDF PNIIDVSIKQ ANQEGSNESR VVTIHKQDGK NLEIELSSLR EALSFVSLID GYYRLTADAH HYLCKEVAPP AVLENIQSNC HGPISMDFAI SKLKKAGNQT GLYVLRCSPK DFNKYFLTFA VERENVIEYK HCLITKNENE EYNLSGTKKN FSSLKDLLNC YQMETVRSDN IIFQFTKCCP PKPKDKSNLL VFRTNGVSDV PTSPTLQRPT HMNQMVFHKI RNEDLIFNES LGQGTFTKIF KGVRREVGDY GQLHETEVLL KVLDKAHRNY SESFFEAASM MSKLSHKHLV LNYGVCVCGD ENILVQEFVK FGSLDTYLKK NKNCINILWK LEVAKQLAWA MHFLEENTLI HGNVCAKNIL LIREEDRKTG NPPFIKLSDP GISITVLPKD ILQERIPWVP PECIENPKNL NLATDKWSFG TTLWEICSGG DKPLSALDSQ RKLQFYEDRH QLPAPKWAEL ANLINNCMDY EPDFRPSFRA IIRDLNSLFT PDYELLTEND MLPNMRIGAL GFSGAFEDRD PTQFEERHLK FLQQLGKGNF GSVEMCRYDP LQDNTGEVVA VKKLQHSTEE HLRDFEREIE ILKSLQHDNI VKYKGVCYSA GRRNLKLIME YLPYGSLRDY LQKHKERIDH IKLLQYTSQI CKGMEYLGTK RYIHRDLATR NILVENENRV KIGDFGLTKV LPQDKEYYKV KEPGESPIFW YAPESLTESK FSVASDVWSF GVVLYELFTY IEKSKSPPAE FMRMIGNDKQ GQMIVFHLIE LLKNNGRLPR PDGCPDEIYM IMTECWNNNV NQRPSFRDLA LRVDQIRDNM AG //