Tyrosine-protein kinase JAK2
| Name | Tyrosine-protein kinase JAK2 |
|---|---|
| Synonyms | 2.7.10.2 JAK-2 Janus kinase 2 |
| Gene Name | JAK2 |
| Organism | Human |
| Amino acid sequence | >lcl|BSEQ0021326|Tyrosine-protein kinase JAK2 MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSG EYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYF PRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLG MAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQF SQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSR GKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLR EALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQT GLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNC YQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKI RNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASM MSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWA MHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVP PECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAEL ANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRD PTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIE ILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQI CKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFW YAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIE LLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG |
| Number of residues | 1132 |
| Molecular Weight | 130672.475 |
| Theoretical pI | 7.21 |
| GO Classification |
Functions
growth hormone receptor binding receptor binding heme binding SH2 domain binding non-membrane spanning protein tyrosine kinase activity histone kinase activity (H3-Y41 specific) protein kinase binding ATP binding protein kinase activity interleukin-12 receptor binding histone binding protein tyrosine kinase activity Processes
hormone-mediated signaling pathway protein phosphorylation positive regulation of tyrosine phosphorylation of Stat3 protein axon guidance interleukin-12-mediated signaling pathway response to lipopolysaccharide tyrosine phosphorylation of STAT protein tyrosine phosphorylation of Stat1 protein Fc-epsilon receptor signaling pathway cellular response to dexamethasone stimulus response to antibiotic positive regulation of protein import into nucleus, translocation Ras protein signal transduction positive regulation of insulin secretion cell differentiation negative regulation of cardiac muscle cell apoptotic process extrinsic apoptotic signaling pathway positive regulation of cell migration negative regulation of neuron apoptotic process tyrosine phosphorylation of Stat3 protein vascular endothelial growth factor receptor signaling pathway axon regeneration cell migration mineralocorticoid receptor signaling pathway cellular response to lipopolysaccharide activation of MAPKK activity positive regulation of cell-substrate adhesion small GTPase mediated signal transduction tyrosine phosphorylation of Stat5 protein G-protein coupled receptor signaling pathway adaptive immune response epidermal growth factor receptor signaling pathway negative regulation of cell-cell adhesion cytokine-mediated signaling pathway positive regulation of sequence-specific DNA binding transcription factor activity apoptotic process activation of cysteine-type endopeptidase activity involved in apoptotic process negative regulation of DNA binding positive regulation of cell proliferation tumor necrosis factor-mediated signaling pathway innate immune response positive regulation of tyrosine phosphorylation of Stat5 protein signal transduction positive regulation of nitric-oxide synthase biosynthetic process fibroblast growth factor receptor signaling pathway actin filament polymerization negative regulation of heart contraction positive regulation of phosphatidylinositol 3-kinase signaling interferon-gamma-mediated signaling pathway peptidyl-tyrosine autophosphorylation histone H3-Y41 phosphorylation response to tumor necrosis factor insulin receptor signaling pathway activation of JAK2 kinase activity regulation of apoptotic process erythrocyte differentiation positive regulation of tumor necrosis factor production regulation of interferon-gamma-mediated signaling pathway peptidyl-tyrosine phosphorylation movement of cell or subcellular component positive regulation of cell differentiation MAPK cascade JAK-STAT cascade involved in growth hormone signaling pathway mesoderm development intracellular signal transduction response to hydroperoxide host programmed cell death induced by symbiont platelet-derived growth factor receptor signaling pathway enzyme linked receptor protein signaling pathway chromatin organization negative regulation of cell proliferation JAK-STAT cascade positive regulation of interleukin-1 beta production positive regulation of inflammatory response mammary gland epithelium development positive regulation of cytosolic calcium ion concentration positive regulation of nitric oxide biosynthetic process positive regulation of phosphoprotein phosphatase activity intrinsic apoptotic signaling pathway in response to oxidative stress neurotrophin TRK receptor signaling pathway positive regulation of DNA binding regulation of inflammatory response positive regulation of cell activation positive regulation of peptidyl-tyrosine phosphorylation protein autophosphorylation blood coagulation activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway positive regulation of transcription from RNA polymerase II promoter growth hormone receptor signaling pathway response to interleukin-12 positive regulation of growth hormone receptor signaling pathway regulation of cell proliferation STAT protein import into nucleus Components
nucleus caveola cytoplasm endosome lumen cytosol nuclear matrix extrinsic component of cytoplasmic side of plasma membrane cytoskeleton nucleoplasm membrane raft |
| General Function | Sh2 domain binding |
| Specific 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. |
| Transmembrane Regions | |
| GenBank Protein ID | |
| UniProtKB ID | O60674 |
| UniProtKB Entry Name | JAK2_HUMAN |
| Cellular Location | Endomembrane system |
| Gene sequence | >lcl|BSEQ0021327|Tyrosine-protein kinase JAK2 (JAK2) ATGGGAATGGCCTGCCTTACGATGACAGAAATGGAGGGAACATCCACCTCTTCTATATAT CAGAATGGTGATATTTCTGGAAATGCCAATTCTATGAAGCAAATAGATCCAGTTCTTCAG GTGTATCTTTACCATTCCCTTGGGAAATCTGAGGCAGATTATCTGACCTTTCCATCTGGG GAGTATGTTGCAGAAGAAATCTGTATTGCTGCTTCTAAAGCTTGTGGTATCACACCTGTG TATCATAATATGTTTGCTTTAATGAGTGAAACAGAAAGGATCTGGTATCCACCCAACCAT GTCTTCCATATAGATGAGTCAACCAGGCATAATGTACTCTACAGAATAAGATTTTACTTT CCTCGTTGGTATTGCAGTGGCAGCAACAGAGCCTATCGGCATGGAATATCTCGAGGTGCT GAAGCTCCTCTTCTTGATGACTTTGTCATGTCTTACCTCTTTGCTCAGTGGCGGCATGAT TTTGTGCACGGATGGATAAAAGTACCTGTGACTCATGAAACACAGGAAGAATGTCTTGGG ATGGCAGTGTTAGATATGATGAGAATAGCCAAAGAAAACGATCAAACCCCACTGGCCATC TATAACTCTATCAGCTACAAGACATTCTTACCAAAATGTATTCGAGCAAAGATCCAAGAC TATCATATTTTGACAAGGAAGCGAATAAGGTACAGATTTCGCAGATTTATTCAGCAATTC AGCCAATGCAAAGCCACTGCCAGAAACTTGAAACTTAAGTATCTTATAAATCTGGAAACT CTGCAGTCTGCCTTCTACACAGAGAAATTTGAAGTAAAAGAACCTGGAAGTGGTCCTTCA GGTGAGGAGATTTTTGCAACCATTATAATAACTGGAAACGGTGGAATTCAGTGGTCAAGA GGGAAACATAAAGAAAGTGAGACACTGACAGAACAGGATTTACAGTTATATTGCGATTTT CCTAATATTATTGATGTCAGTATTAAGCAAGCAAACCAAGAGGGTTCAAATGAAAGCCGA GTTGTAACTATCCATAAGCAAGATGGTAAAAATCTGGAAATTGAACTTAGCTCATTAAGG GAAGCTTTGTCTTTCGTGTCATTAATTGATGGATATTATAGATTAACTGCAGATGCACAT CATTACCTCTGTAAAGAAGTAGCACCTCCAGCCGTGCTTGAAAATATACAAAGCAACTGT CATGGCCCAATTTCGATGGATTTTGCCATTAGTAAACTGAAGAAAGCAGGTAATCAGACT GGACTGTATGTACTTCGATGCAGTCCTAAGGACTTTAATAAATATTTTTTGACTTTTGCT GTCGAGCGAGAAAATGTCATTGAATATAAACACTGTTTGATTACAAAAAATGAGAATGAA GAGTACAACCTCAGTGGGACAAAGAAGAACTTCAGCAGTCTTAAAGATCTTTTGAATTGT TACCAGATGGAAACTGTTCGCTCAGACAATATAATTTTCCAGTTTACTAAATGCTGTCCC CCAAAGCCAAAAGATAAATCAAACCTTCTAGTCTTCAGAACGAATGGTGTTTCTGATGTA CCAACCTCACCAACATTACAGAGGCCTACTCATATGAACCAAATGGTGTTTCACAAAATC AGAAATGAAGATTTGATATTTAATGAAAGCCTTGGCCAAGGCACTTTTACAAAGATTTTT AAAGGCGTACGAAGAGAAGTAGGAGACTACGGTCAACTGCATGAAACAGAAGTTCTTTTA AAAGTTCTGGATAAAGCACACAGAAACTATTCAGAGTCTTTCTTTGAAGCAGCAAGTATG ATGAGCAAGCTTTCTCACAAGCATTTGGTTTTAAATTATGGAGTATGTGTCTGTGGAGAC GAGAATATTCTGGTTCAGGAGTTTGTAAAATTTGGATCACTAGATACATATCTGAAAAAG AATAAAAATTGTATAAATATATTATGGAAACTTGAAGTTGCTAAACAGTTGGCATGGGCC ATGCATTTTCTAGAAGAAAACACCCTTATTCATGGGAATGTATGTGCCAAAAATATTCTG CTTATCAGAGAAGAAGACAGGAAGACAGGAAATCCTCCTTTCATCAAACTTAGTGATCCT GGCATTAGTATTACAGTTTTGCCAAAGGACATTCTTCAGGAGAGAATACCATGGGTACCA CCTGAATGCATTGAAAATCCTAAAAATTTAAATTTGGCAACAGACAAATGGAGTTTTGGT ACCACTTTGTGGGAAATCTGCAGTGGAGGAGATAAACCTCTAAGTGCTCTGGATTCTCAA AGAAAGCTACAATTTTATGAAGATAGGCATCAGCTTCCTGCACCAAAGTGGGCAGAATTA GCAAACCTTATAAATAATTGTATGGATTATGAACCAGATTTCAGGCCTTCTTTCAGAGCC ATCATACGAGATCTTAACAGTTTGTTTACTCCAGATTATGAACTATTAACAGAAAATGAC ATGTTACCAAATATGAGGATAGGTGCCCTGGGGTTTTCTGGTGCCTTTGAAGACCGGGAT CCTACACAGTTTGAAGAGAGACATTTGAAATTTCTACAGCAACTTGGCAAGGGTAATTTT GGGAGTGTGGAGATGTGCCGGTATGACCCTCTACAGGACAACACTGGGGAGGTGGTCGCT GTAAAAAAGCTTCAGCATAGTACTGAAGAGCACCTAAGAGACTTTGAAAGGGAAATTGAA ATCCTGAAATCCCTACAGCATGACAACATTGTAAAGTACAAGGGAGTGTGCTACAGTGCT GGTCGGCGTAATCTAAAATTAATTATGGAATATTTACCATATGGAAGTTTACGAGACTAT CTTCAAAAACATAAAGAACGGATAGATCACATAAAACTTCTGCAGTACACATCTCAGATA TGCAAGGGTATGGAGTATCTTGGTACAAAAAGGTATATCCACAGGGATCTGGCAACGAGA AATATATTGGTGGAGAACGAGAACAGAGTTAAAATTGGAGATTTTGGGTTAACCAAAGTC TTGCCACAAGACAAAGAATACTATAAAGTAAAAGAACCTGGTGAAAGTCCCATATTCTGG TATGCTCCAGAATCACTGACAGAGAGCAAGTTTTCTGTGGCCTCAGATGTTTGGAGCTTT GGAGTGGTTCTGTATGAACTTTTCACATACATTGAGAAGAGTAAAAGTCCACCAGCGGAA TTTATGCGTATGATTGGCAATGACAAACAAGGACAGATGATCGTGTTCCATTTGATAGAA CTTTTGAAGAATAATGGAAGATTACCAAGACCAGATGGATGCCCAGATGAGATCTATATG ATCATGACAGAATGCTGGAACAATAATGTAAATCAACGCCCCTCCTTTAGGGATCTAGCT CTTCGAGTGGATCAAATAAGGGATAACATGGCTGGATGA |
| GenBank Gene ID | AF058925 |
| GeneCard ID | None |
| GenAtlas ID | JAK2 |
| HGNC ID | HGNC:6192 |
| Chromosome Location | 9 |
| Locus | 9p24 |
| References |
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Related FRC
| FRCD ID | Name | Exact Mass | Structure |
|---|---|---|---|
Thiabendazole |
201.247 |
||
Thiram |
240.416 |