Aliases for JAK2 Gene
External Ids for JAK2 Gene
Previous GeneCards Identifiers for JAK2 Gene
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, Jul 2008]
JAK2 is a kinase that is misregulated or mutated in a number of myeloproliferative diseases and cancers. The mutation V617F is the most clinically relevant variant, and is seen in around half of myeloproliferative disorders. The variant is a known activating mutation, and activated JAK2 is sufficient to drive myeloproliferative disorders in mouse models. V617F, while most recurrent, is not the only mechanism by which JAK2 can be activated in patients. JAK2 is now one of the first diagnostic markers tested upon diagnosis with a myeloproliferative disorder.
GeneCards Summary for JAK2 Gene
JAK2 (Janus Kinase 2) is a Protein Coding gene. Diseases associated with JAK2 include Polycythemia Vera and Thrombocythemia 3. Among its related pathways are Negative regulation of MAPK pathway and RET signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is JAK3.
UniProtKB/Swiss-Prot Summary for JAK2 Gene
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 (PubMed:7615558). 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: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. 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).
JAKs (or Janus kinases) are a family of tyrosine kinases that are associated with cytokine receptors. Upon receptor activation JAKs phosphorylate the transcription factors known as STATs and initiate the JAK-STAT signaling pathway. Four JAK family members have been identified.