JAK2 (pY1007/Y1008) Antibody – Rabbit

This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. [provided by RefSeq]

Function: Non-receptor tyrosine kinase involved in various processes such as cell cycle progression, apoptosis, mitotic recombination, genetic instability and histone modifications. In the cytoplasm, plays a pivotal role in signal transduction via its association with cytokine receptors, which constitutes an initiating step in signaling for many members of the cytokine receptor superfamily including the receptors for growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), granulocyte-macrophage colony-stimulating factor (CSF2), thrombopoietin (THPO) and multiple interleukins. Following stimulation with erythropoietin (EPO) during erythropoiesis, it is autophosphorylated and activated, leading to its association with erythropoietin receptor (EPOR) and tyrosine phosphorylation of residues in the EPOR cytoplasmic domain. Also involved in promoting the localization of EPOR to the plasma membrane. Also acts downstream of some G-protein coupled receptors. Plays a role in the control of body weight

By similarity. Mediates angiotensin-2-induced ARHGEF1 phosphorylation. 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. Ref.7 Ref.14 Ref.16

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme 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. Ref.15

Subunit structure: Interacts with EPOR, SIRPA and SH2B1

By similarity. Interacts with IL23R, SKB1 and STAM2. Ref.5 Ref.6 Ref.7

Subcellular location: Endomembrane system; Peripheral membrane protein

By similarity. Nucleus Ref.14.

Tissue specificity: Expressed in blood, bone marrow and lymph node. Ref.12

Domain: Possesses 2 protein kinase domains. The second one probably contains the catalytic domain, while the presence of slight differences suggest a different role for protein kinase 1

Post-translational modification: Autophosphorylated, leading to regulate its activity. Leptin promotes phosphorylation on tyrosine residues, including phosphorylation on Tyr-813. Autophosphorylation on Tyr-119 in response to EPO down-regulates its kinase activity. Autophosphorylation on Tyr-868, Tyr-966 and Tyr-972 in response to growth hormone (GH) are required for maximal kinase activity

By similarity. Ref.13 Ref.17

Involvement in 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.Defects in JAK2 are a cause of susceptibility to Budd-Chiari syndrome (BCS) [

MIM:600880]. It is 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.Defects in JAK2 are a cause of 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. Ref.18 Ref.21 Ref.22 Ref.25Defects 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. Ref.3 Ref.20Defects in JAK2 are a cause of myelofibrosis (MYELOF) [

MIM:254450]. Myelofibrosis is 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.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. Ref.24

Sequence similarities: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.Contains 1 FERM domain.Contains 1 protein kinase domain.Contains 1 SH2 domain.