NameTyrosine-protein kinase JAK2
Synonyms
  • 2.7.10.2
  • JAK-2
  • Janus kinase 2
Gene NameJAK2
OrganismHuman
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 residues1132
Molecular Weight130672.475
Theoretical pI7.21
GO Classification
Functions
  • heme binding
  • protein tyrosine kinase activity
  • histone binding
  • ATP binding
  • protein kinase activity
  • SH2 domain binding
  • interleukin-12 receptor binding
  • protein kinase binding
  • receptor binding
  • non-membrane spanning protein tyrosine kinase activity
  • histone kinase activity (H3-Y41 specific)
  • growth hormone receptor binding
Processes
  • positive regulation of inflammatory response
  • response to hydroperoxide
  • activation of MAPKK activity
  • negative regulation of neuron apoptotic process
  • tyrosine phosphorylation of Stat3 protein
  • regulation of inflammatory response
  • positive regulation of nitric oxide biosynthetic process
  • host programmed cell death induced by symbiont
  • apoptotic process
  • positive regulation of cell-substrate adhesion
  • tyrosine phosphorylation of Stat5 protein
  • mammary gland epithelium development
  • signal transduction
  • fibroblast growth factor receptor signaling pathway
  • activation of cysteine-type endopeptidase activity involved in apoptotic process
  • negative regulation of DNA binding
  • axon guidance
  • response to lipopolysaccharide
  • STAT protein import into nucleus
  • positive regulation of cell activation
  • insulin receptor signaling pathway
  • negative regulation of heart contraction
  • erythrocyte differentiation
  • cell differentiation
  • tyrosine phosphorylation of STAT protein
  • positive regulation of growth hormone receptor signaling pathway
  • MAPK cascade
  • activation of JAK2 kinase activity
  • mesoderm development
  • cell migration
  • cellular response to lipopolysaccharide
  • extrinsic apoptotic signaling pathway
  • tyrosine phosphorylation of Stat1 protein
  • enzyme linked receptor protein signaling pathway
  • negative regulation of cell proliferation
  • JAK-STAT cascade involved in growth hormone signaling pathway
  • positive regulation of interleukin-1 beta production
  • epidermal growth factor receptor signaling pathway
  • cytokine-mediated signaling pathway
  • neurotrophin TRK receptor signaling pathway
  • JAK-STAT cascade
  • innate immune response
  • positive regulation of sequence-specific DNA binding transcription factor activity
  • blood coagulation
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of DNA binding
  • growth hormone receptor signaling pathway
  • response to interleukin-12
  • peptidyl-tyrosine autophosphorylation
  • positive regulation of tyrosine phosphorylation of Stat5 protein
  • positive regulation of nitric-oxide synthase biosynthetic process
  • protein phosphorylation
  • positive regulation of tyrosine phosphorylation of Stat3 protein
  • interleukin-12-mediated signaling pathway
  • peptidyl-tyrosine phosphorylation
  • response to tumor necrosis factor
  • response to antibiotic
  • Ras protein signal transduction
  • positive regulation of insulin secretion
  • negative regulation of cardiac muscle cell apoptotic process
  • platelet-derived growth factor receptor signaling pathway
  • movement of cell or subcellular component
  • positive regulation of cell differentiation
  • vascular endothelial growth factor receptor signaling pathway
  • G-protein coupled receptor signaling pathway
  • axon regeneration
  • mineralocorticoid receptor signaling pathway
  • positive regulation of cytosolic calcium ion concentration
  • chromatin organization
  • small GTPase mediated signal transduction
  • positive regulation of cell proliferation
  • adaptive immune response
  • negative regulation of cell-cell adhesion
  • positive regulation of peptidyl-tyrosine phosphorylation
  • positive regulation of phosphoprotein phosphatase activity
  • intrinsic apoptotic signaling pathway in response to oxidative stress
  • positive regulation of phosphatidylinositol 3-kinase signaling
  • tumor necrosis factor-mediated signaling pathway
  • regulation of cell proliferation
  • protein autophosphorylation
  • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
  • actin filament polymerization
  • positive regulation of tumor necrosis factor production
  • interferon-gamma-mediated signaling pathway
  • histone H3-Y41 phosphorylation
  • Fc-epsilon receptor signaling pathway
  • hormone-mediated signaling pathway
  • regulation of apoptotic process
  • intracellular signal transduction
  • regulation of interferon-gamma-mediated signaling pathway
  • positive regulation of cell migration
  • cellular response to dexamethasone stimulus
  • positive regulation of protein import into nucleus, translocation
Components
  • extrinsic component of cytoplasmic side of plasma membrane
  • nucleoplasm
  • cytoplasm
  • membrane raft
  • endosome lumen
  • caveola
  • cytoskeleton
  • nucleus
  • nuclear matrix
  • cytosol
General FunctionSh2 domain binding
Specific FunctionNon-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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDO60674
UniProtKB Entry NameJAK2_HUMAN
Cellular LocationEndomembrane 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 IDAF058925
GeneCard IDNot Available
GenAtlas IDJAK2
HGNC IDHGNC:6192
Chromosome Location9
Locus9p24
References
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