Catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ,Disease: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:Defects in JAK2 are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. ,Disease:Defects in JAK2 are a cause of susceptibility to Budd-Chiari syndrome [MIM:600880]. Budd-Chiari syndrome is a spectrum of disease states , including anatomic abnormalities and hypercoagulable disorders , resulting in hepatic venous outflow occlusion. Clinical manifestations observed in the majority of patients include hepatomegaly , right upper quadrant pain , and abdominal ascites. ,Disease:Defects in JAK2 are associated with familial myelofibrosis [MIM:254450]. Myelofibrosis with myeloid metaplasia is a myeloproliferative disease with annual incidence of 0.5-1.5 cases per 100 ,000 individuals and age at diagnosis around 60 (an increased prevalence is noted in Ashkenazi Jews) . Clinical manifestations depend on the type of blood cell affected and may include anemia , pallor , splenomegaly , hypermetabolic state , petechiae , ecchymosis , bleeding , lymphadenopathy , hepatomegaly , portal hypertension. ,Disease:Defects in JAK2 are associated with polycythemia vera (PV) [MIM:263300]. PV , the most common form of primary polycythemia , is caused by somatic mutation in a single hematopoietic stem cell leading to clonal hematopoiesis. PV is a myeloproliferative disorder characterized predominantly by erythroid hyperplasia , but also by myeloid leukocytosis , thrombocytosis , and splenomegaly. Familial cases of PV are very rare and usually manifest in elderly patients. ,Disease:Defects in JAK2 gene may be a cause of essential thrombocythemia (ET) [MIM:187950]. ET is characterized by elevated platelet levels due to sustained proliferation of megakaryocytes , and frequently lead to thrombotic and haemorrhagic complications. ,Domain:Possesses two phosphotransferase domains. The second one probably contains the catalytic domain (By similarity) , while the presence of slight differences suggest a different role for domain 1. ,Function:Plays a role in leptin signaling and control of body weight (By similarity) . Tyrosine kinase of the non-receptor type , involved in interleukin-3 and probably interleukin-23 signal transduction. ,PTM:Leptin promotes phosphorylation on tyrosine residues , including phosphorylation on Tyr-813. ,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. ,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. ,similarity:Contains 1 FERM domain. ,similarity:Contains 1 protein kinase domain. ,similarity:Contains 1 SH2 domain. ,subcellular location:Wholly intracellular , possibly membrane associated. ,subunit:Interacts with SIRPA and SH2B1 (By similarity) . Interacts with IL23R , SKB1 and STAM2. ,tissue specificity:Expressed in blood , bone marrow and lymph node. ,
展开内容