JAK2 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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B). 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. Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily. Ubiquitously expressed throughout most tissues. Note: This description may include information from UniProtKB.
Protein type: EC; JakA family; Kinase, protein; Oncoprotein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); TK group
Chromosomal Location of Human Ortholog: 9p24.1
Cellular Component:  caveola; cytoplasm; cytoskeleton; cytosol; endosome lumen; focal adhesion; glutamatergic synapse; membrane raft; nuclear matrix; nucleoplasm; nucleus; plasma membrane; postsynapse
Molecular Function:  acetylcholine receptor binding; ATP binding; growth hormone receptor binding; heme binding; histone binding; histone kinase activity (H3-Y41 specific); identical protein binding; insulin receptor substrate binding; interleukin-12 receptor binding; metal ion binding; non-membrane spanning protein tyrosine kinase activity; peptide hormone receptor binding; phosphatidylinositol 3-kinase binding; protein binding; protein C-terminus binding; protein kinase activity; protein kinase binding; protein tyrosine kinase activity; SH2 domain binding; signaling receptor binding; type 1 angiotensin receptor binding
Biological Process:  actin filament polymerization; activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; activation of Janus kinase activity; activation of MAPKK activity; adaptive immune response; apoptotic process; axon regeneration; blood coagulation; cell differentiation; cytokine-mediated signaling pathway; enzyme linked receptor protein signaling pathway; erythrocyte differentiation; extrinsic apoptotic signaling pathway; G protein-coupled receptor signaling pathway; growth hormone receptor signaling pathway; histone H3-Y41 phosphorylation; interferon-gamma-mediated signaling pathway; interleukin-12-mediated signaling pathway; interleukin-23-mediated signaling pathway; interleukin-27-mediated signaling pathway; interleukin-35-mediated signaling pathway; interleukin-6-mediated signaling pathway; intracellular signal transduction; intrinsic apoptotic signaling pathway in response to oxidative stress; JAK-STAT cascade; JAK-STAT cascade involved in growth hormone signaling pathway; mammary gland epithelium development; MAPK cascade; mesoderm development; mineralocorticoid receptor signaling pathway; modulation of chemical synaptic transmission; negative regulation of cardiac muscle cell apoptotic process; negative regulation of cell proliferation; negative regulation of cell-cell adhesion; negative regulation of DNA binding; negative regulation of heart contraction; negative regulation of neuron apoptotic process; peptidyl-tyrosine phosphorylation; platelet-derived growth factor receptor signaling pathway; positive regulation of cell activation; positive regulation of cell differentiation; positive regulation of cell migration; positive regulation of cell-substrate adhesion; positive regulation of cold-induced thermogenesis; positive regulation of cytosolic calcium ion concentration; positive regulation of DNA binding; positive regulation of DNA-binding transcription factor activity; positive regulation of epithelial cell apoptotic process; positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; positive regulation of growth hormone receptor signaling pathway; positive regulation of inflammatory response; positive regulation of insulin secretion; positive regulation of interleukin-1 beta production; positive regulation of nitric oxide biosynthetic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of phosphoprotein phosphatase activity; positive regulation of Ras protein signal transduction; positive regulation of tumor necrosis factor production; positive regulation of tyrosine phosphorylation of STAT protein; positive regulation of vascular smooth muscle cell proliferation; postsynapse to nucleus signaling pathway; protein autophosphorylation; protein phosphorylation; regulation of inflammatory response; regulation of interferon-gamma-mediated signaling pathway; regulation of JAK-STAT cascade; regulation of nitric oxide biosynthetic process; response to antibiotic; response to hydroperoxide; response to interleukin-12; response to lipopolysaccharide; response to tumor necrosis factor; signal transduction; tumor necrosis factor-mediated signaling pathway; tyrosine phosphorylation of STAT protein
Disease: Budd-chiari Syndrome; Erythrocytosis, Familial, 1; Leukemia, Acute Myeloid; Myelofibrosis; Polycythemia Vera; Thrombocythemia 3
Reference #:  O60674 (UniProtKB)
Alt. Names/Synonyms: JAK-2; JAK2; Janus kinase 2; Janus kinase 2 (a protein tyrosine kinase); JTK10; Tyrosine-protein kinase JAK2
Gene Symbols: JAK2
Molecular weight: 130,674 Da
Basal Isoelectric point: 6.82  Predict pI for various phosphorylation states
CST Pathways:  ErbB/HER Signaling  |  IL6 Signaling  |  Inhibition of Apoptosis  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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