JAK2_HUMAN
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 03-AUG-2022, entry version 232.
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)74230-6;
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-GLN-LEU-539 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 TEC
CC 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="http://atlasgeneticsoncology.org/Genes/JAKID98.html";
CC ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; O60674; -.
DR SMR; O60674; -.
DR BioGRID; 109920; 148.
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; 43.
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; DB11817; Baricitinib.
DR DrugBank; DB11986; Entrectinib.
DR DrugBank; DB12500; Fedratinib.
DR DrugBank; DB12010; Fostamatinib.
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 iPTMnet; O60674; -.
DR PhosphoSitePlus; O60674; -.
DR BioMuta; JAK2; -.
DR CPTAC; CPTAC-1252; -.
DR EPD; O60674; -.
DR jPOST; O60674; -.
DR MassIVE; O60674; -.
DR MaxQB; O60674; -.
DR PaxDb; O60674; -.
DR PeptideAtlas; O60674; -.
DR PRIDE; O60674; -.
DR ProteomicsDB; 49519; -.
DR Antibodypedia; 24086; 1246 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 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; ICAVACK; -.
DR OrthoDB; 58906at2759; -.
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-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; 29 hits in 1121 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 183 other tissues.
DR ExpressionAtlas; O60674; baseline and differential.
DR Genevisible; O60674; HS.
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: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; IC:ComplexPortal.
DR GO; GO:0072536; C:interleukin-23 receptor complex; IC:ComplexPortal.
DR GO; GO:0045121; C:membrane raft; ISS:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
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:0005126; F:cytokine receptor binding; IBA:GO_Central.
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 kinase activity (H3-Y41 specific); 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:0008022; F:protein C-terminus 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; IC:ComplexPortal.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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; IC:ComplexPortal.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0070757; P:interleukin-35-mediated signaling pathway; TAS:Reactome.
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:0045822; P:negative regulation of heart contraction; IEA:Ensembl.
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:0043388; P:positive regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; 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:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:ComplexPortal.
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; IC: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:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:BHF-UCL.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IEA:Ensembl.
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; IC: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: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:0099527; P:postsynapse to nucleus signaling pathway; IEA:Ensembl.
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; IDA:ComplexPortal.
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: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:0007260; P:tyrosine phosphorylation of STAT protein; ISS:BHF-UCL.
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; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR035963; FERM_2.
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 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
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.
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 /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; associated with
FT susceptibility to Budd-Chiari syndrome; somatic mutation in
FT a high percentage of patients with essential
FT thrombocythemia or myelofibrosis; leads to constitutive
FT tyrosine 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:5UT3"
FT STRAND 545..554
FT /evidence="ECO:0007829|PDB:5UT3"
FT STRAND 557..567
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:5UT3"
FT STRAND 573..583
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 585..590
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 591..602
FT /evidence="ECO:0007829|PDB:5UT3"
FT STRAND 612..616
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 618..620
FT /evidence="ECO:0007829|PDB:6G3C"
FT STRAND 623..627
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 634..640
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 642..644
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 647..666
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 676..678
FT /evidence="ECO:0007829|PDB:5UT3"
FT STRAND 679..683
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 687..689
FT /evidence="ECO:0007829|PDB:5UT3"
FT STRAND 694..697
FT /evidence="ECO:0007829|PDB:5UT3"
FT TURN 704..706
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 709..714
FT /evidence="ECO:0007829|PDB:5UT3"
FT TURN 715..718
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 721..725
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 727..729
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 732..747
FT /evidence="ECO:0007829|PDB:5UT3"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:5UT3"
FT TURN 753..756
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 759..767
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 778..780
FT /evidence="ECO:0007829|PDB:5I4N"
FT HELIX 781..787
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 792..794
FT /evidence="ECO:0007829|PDB:5UT3"
FT HELIX 798..807
FT /evidence="ECO:0007829|PDB:5UT3"
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:4D1S"
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
