JAK2
entrez
3717
canonical
uniprot
O60674
canonical
ensembl
ENSG00000096968
resolver
ensp
ENSP00000371067
resolver
ensp
ENSP00000540379
resolver
ensp
ENSP00000540380
resolver
ensp
ENSP00000540381
resolver
ensp
ENSP00000540382
resolver
ensp
ENSP00000540383
resolver
ensp
ENSP00000633996
resolver
ensp
ENSP00000633997
resolver
ensp
ENSP00000633999
resolver
ensp
ENSP00000634000
resolver
enst
ENST00000381652
resolver
enst
ENST00000870320
resolver
enst
ENST00000870321
resolver
enst
ENST00000870322
resolver
enst
ENST00000870323
resolver
enst
ENST00000870324
resolver
enst
ENST00000963937
resolver
enst
ENST00000963938
resolver
enst
ENST00000963940
resolver
enst
ENST00000963941
resolver
genesymbol
JAK2
resolver
hgnc
HGNC:6192
resolver
uniprot
A8K910
resolver
uniprot
B4DYV1
resolver
uniprot
O14636
resolver
uniprot
O75297
resolver
uniprot_entry
A8K910_HUMAN
resolver
uniprot_entry
B4DYV1_HUMAN
resolver
uniprot_entry
JAK2_HUMAN
resolver
uniprot_sec
O14636
resolver
uniprot_sec
O75297
resolver
activity_regulation
ACTIVITY REGULATION: Regulated by autophosphorylation, can both activate or decrease activity (By similarity). Heme regulates its activity by enhancing the phosphorylation on Tyr-1007 and Tyr-1008 (PubMed:21036157). {ECO:0000250|UniProtKB:Q62120, ECO:0000269|PubMed:21036157}.
uniprot
proteins
amino_acid_sequence
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLREALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG
uniprot
proteins
disease_involvement
DISEASE: Note=Chromosomal aberrations involving JAK2 are found in both chronic and acute forms of eosinophilic, lymphoblastic and myeloid leukemia. Translocation t(8;9)(p22;p24) with PCM1 links the protein kinase domain of JAK2 to the major portion of PCM1. Translocation t(9;12)(p24;p13) with ETV6.; DISEASE: Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. {ECO:0000269|PubMed:16707754}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Polycythemia vera (PV) [MIM:263300]: A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. {ECO:0000269|PubMed:15781101, ECO:0000269|PubMed:15793561, ECO:0000269|PubMed:15858187, ECO:0000269|PubMed:16603627, ECO:0000269|PubMed:25644777}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Thrombocythemia 3 (THCYT3) [MIM:614521]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. {ECO:0000269|PubMed:16325696, ECO:0000269|PubMed:22397670}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Myelofibrosis (MYELOF) [MIM:254450]: A disorder characterized by replacement of the bone marrow by fibrous tissue, occurring in association with a myeloproliferative disorder. Clinical manifestations may include anemia, pallor, splenomegaly, hypermetabolic state, petechiae, ecchymosis, bleeding, lymphadenopathy, hepatomegaly, portal hypertension. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:16247455}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
FUNCTION: Non-membrane spanning protein tyrosine kinase that phosphorylates type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:15899890, PubMed:7615558, PubMed:9188471, PubMed:9657743). Functionally, plays a pivotal role in signal transduction and is involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. Mechanistically, following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). Binding of CNTF or the CLCF1/CLF heterodimer to CNTFR leads to IL6ST/gp130-LIFR dimerization followed by activation of JAK1 and JAK2 which in turns phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking proteins for STAT3 (PubMed:11294841). Involved in the oncostatin-M-mediated signaling pathway through both type I OSM receptor complex (heterodimers composed of LIFR and IL6ST) and type II OSM receptor complex (heterodimers composed of OSMR and IL6ST) (PubMed:9188471). {ECO:0000269|PubMed:11294841, ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9188471, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}.
uniprot
proteins
mass_dalton
130674
uniprot
proteins
mutagenesis
MUTAGEN 882; /note="K->E: Loss of ability to up-regulate potassium voltage-gated channel activity of KCNA3."; /evidence="ECO:0000269|PubMed:25644777
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813 (By similarity). Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity (By similarity). Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity (By similarity). Also phosphorylated by TEC (By similarity). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558, PubMed:7673114). Phosphorylated on tyrosine residues in response to a signaling cascade that is activated by increased cellular retinol (PubMed:21368206). {ECO:0000250|UniProtKB:Q62120, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7673114}.; PTM: Undergoes Notch-induced ubiquitination and subsequent proteasomal degradation which is mediated by ASB1 or ASB2, the substrate-recognition components of probable ECS E3 ubiquitin-protein ligase complexes. {ECO:0000269|PubMed:21119685}.
uniprot
proteins
protein_family
JAK subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10531356
uniprot
proteins
pubmed
10899310
uniprot
proteins
pubmed
11294841
uniprot
proteins
pubmed
12023369
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15690087
uniprot
proteins
pubmed
15781101
uniprot
proteins
pubmed
15793561
uniprot
proteins
pubmed
15805263
uniprot
proteins
pubmed
15858187
uniprot
proteins
pubmed
15899890
uniprot
proteins
pubmed
16034466
uniprot
proteins
pubmed
16091753
uniprot
proteins
pubmed
16174768
uniprot
proteins
pubmed
16247455
uniprot
proteins
pubmed
16325696
uniprot
proteins
pubmed
16424865
uniprot
proteins
pubmed
16456223
uniprot
proteins
pubmed
16603627
uniprot
proteins
pubmed
16707754
uniprot
proteins
pubmed
16769584
uniprot
proteins
pubmed
17267906
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
19290934
uniprot
proteins
pubmed
19783980
uniprot
proteins
pubmed
20098430
uniprot
proteins
pubmed
20353823
uniprot
proteins
pubmed
21036157
uniprot
proteins
pubmed
21119685
uniprot
proteins
pubmed
21368206
uniprot
proteins
pubmed
21423214
uniprot
proteins
pubmed
22397670
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25092874
uniprot
proteins
pubmed
25644777
uniprot
proteins
pubmed
7615558
uniprot
proteins
pubmed
7673114
uniprot
proteins
pubmed
9188471
uniprot
proteins
pubmed
9326218
uniprot
proteins
pubmed
9446644
uniprot
proteins
pubmed
9618263
uniprot
proteins
pubmed
9657743
uniprot
proteins
sequence_length
1132
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:19783980}. Nucleus {ECO:0000269|PubMed:19783980}.
uniprot
proteins