JAK2_HUMAN
Source:
PM23856902
Marked as 'Membrane associated protein'
Confidence:
low (only semi-automatic identification from reviews)
Search PubMed for
(RBC AND this entry)
Gene names:
JAK2
Protein names and data:
JAK2_HUMAN
, Tyrosine-protein kinase JAK2; 2.7.10.2
, Janus kinase 2; JAK-2
Lenght: 1132 a.a.
Mass: 130674 Da
fasta formatted sequence
Function:
Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.
Catalytic activity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Disease:
( OMIM:
147796
254450
263300
600880
601626
614521
)
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. 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. 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. Note=The disease is caused by mutations affecting the gene represented in this entry. 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. Note=The disease may be caused by mutations affecting the gene represented in this entry. 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 mutations affecting the gene represented in this entry. 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Cellular location:
Endomembrane system; Peripheral membrane protein (By similarity). Cytoplasm. Nucleus.
Tissue specificity:
Ubiquitously expressed throughout most tissues.
Genetic variants
127 - 127
G -> D (in dbSNP:rs56118985). VAR_041716
56118985
191 - 191
K -> Q (in an ovarian serous carcinoma sample; somatic mutation). VAR_041717
346 - 346
K -> R (in dbSNP:rs55667734). VAR_041718
55667734
377 - 377
A -> E (in dbSNP:rs55953208). VAR_041719
55953208
393 - 393
L -> V (in dbSNP:rs2230723). VAR_041720
2230723
537 - 539
FHK -> L (in myeloproliferative disorder with erythrocytosis). VAR_032693
538 - 539
HK -> QL (in myeloproliferative disorder with erythrocytosis). VAR_032694
539 - 539
K -> L (in myeloproliferative disorder with erythrocytosis; requires 2 nucleotide substitutions). VAR_032695
584 - 584
D -> E (in dbSNP:rs17490221). VAR_043129
17490221
607 - 607
K -> N (in AML). VAR_032696
617 - 617
V -> F (in PV, THCYT3 and AML; associated with susceptibility to Budd-Chiari syndrome; somatic mutation in a high percentage of patients with essential thrombocythemia or myelofibrosis; leads to constitutive tyrosine phosphorylation activity that promotes cytokine hypersensitivity). VAR_032697
617 - 617
V -> I (in THCYT3). VAR_067534
1063 - 1063
R -> H (in dbSNP:rs41316003). VAR_041721
41316003
Database cross-references
UniProt:
O60674
Ensembl:
ENST00000381652
Ensembl:
ENST00000539801
MIM:
147796
MIM:
254450
MIM:
263300
MIM:
600880
MIM:
601626
MIM:
614521
neXtProt:
NX_O60674
Antibodypedia:
O60674
(may not find the protein thus also not any antibody)
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