JAK2 - Tyrosine-protein kinase JAK2 - human protein (Function)
 
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JAK2 »  Tyrosine-protein kinase JAK2   [ EC 2.7.10.2 ]
 
Protein also known as:  Janus kinase 2 (JAK-2).
Gene name:  JAK2
Entry whose protein(s) existence is based on evidence at protein level
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1 1017 1
GENE REF ISO

Function

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Overview 
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.  
5
  • UniProtKB
GO molecular function 
Acetylcholine receptor bindingdefinition[GO:0033130] silver  
1
  • Ortholog Compara
ATP bindingdefinition[GO:0005524]  
1
  • UniProtKB KW
Growth hormone receptor bindingdefinition[GO:0005131]  
2
  • RefGenome
  • Ortholog Curator
Heme bindingdefinition[GO:0020037]  
1
  • UniProtKB
Histone bindingdefinition[GO:0042393]  
1
  • UniProtKB
Histone kinase activity (H3-Y41 specific)definition[GO:0035401]  
1
  • UniProtKB
Insulin receptor substrate bindingdefinition[GO:0043560] silver  
1
  • Ortholog Compara
Interleukin-12 receptor bindingdefinition[GO:0005143]  
1
  • Ortholog Curator
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • RefGenome
Peptide hormone receptor bindingdefinition[GO:0051428] silver  
1
  • Ortholog Compara
Phosphatidylinositol 3-kinase bindingdefinition[GO:0043548] silver  
1
  • Ortholog Compara
Protein bindingdefinition[GO:0005515]  
8
  • IntAct
  • UniProtKB
Protein C-terminus bindingdefinition[GO:0008022] silver  
1
  • Ortholog Compara
Protein kinase activitydefinition[GO:0004672]  
1
  • PINC
Protein kinase bindingdefinition[GO:0019901]  
1
  • BHF-UCL
Protein tyrosine kinase activitydefinition[GO:0004713]  
2
  • CACAO
  • Ortholog Curator
Receptor bindingdefinition[GO:0005102]  
1
  • UniProtKB
SH2 domain bindingdefinition[GO:0042169]  
1
  • UniProtKB
Type 1 angiotensin receptor bindingdefinition[GO:0031702] silver  
1
  • Ortholog Compara
GO biological process 
Actin filament polymerizationdefinition[GO:0030041]  
1
  • BHF-UCL
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
1
  • Ortholog Curator
Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathwaydefinition[GO:0097296]  
1
  • Ortholog Curator
Activation of JAK2 kinase activitydefinition[GO:0042977]  
1
  • Ortholog Curator
Activation of MAPKK activitydefinition[GO:0000186] silver  
1
  • Ortholog Compara
Apoptotic processdefinition[GO:0006915]  
1
  • Ortholog Curator
Axon regenerationdefinition[GO:0031103] silver  
1
  • Ortholog Compara
Cell differentiationdefinition[GO:0030154]  
1
  • Ortholog Curator
Cell migrationdefinition[GO:0016477]  
1
  • RefGenome
Cytokine-mediated signaling pathwaydefinition[GO:0019221]  
2
  • BHF-UCL
  • Ortholog Curator
Enzyme linked receptor protein signaling pathwaydefinition[GO:0007167]  
1
  • Ortholog Curator
Erythrocyte differentiationdefinition[GO:0030218]  
2
  • Ortholog Curator
  • RefGenome
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
1
  • Ortholog Curator
G-protein coupled receptor signaling pathwaydefinition[GO:0007186] silver  
1
  • Ortholog Compara
Growth hormone receptor signaling pathwaydefinition[GO:0060396]  
1
  • BHF-UCL
Histone H3-Y41 phosphorylationdefinition[GO:0035409]  
1
  • UniProtKB
Hormone-mediated signaling pathwaydefinition[GO:0009755] silver  
1
  • Ortholog Compara
Host programmed cell death induced by symbiontdefinition[GO:0034050] silver  
1
  • Ortholog Compara
Innate immune responsedefinition[GO:0045087]  
1
  • RefGenome
Interleukin-12-mediated signaling pathwaydefinition[GO:0035722]  
1
  • BHF-UCL
Intracellular signal transductiondefinition[GO:0035556]  
1
  • Ortholog Curator
Intrinsic apoptotic signaling pathway in response to oxidative stressdefinition[GO:0008631] silver  
1
  • Ortholog Compara
JAK-STAT cascadedefinition[GO:0007259]  
1
  • PINC
JAK-STAT cascade involved in growth hormone signaling pathwaydefinition[GO:0060397]  
1
  • Ortholog Curator
Mammary gland epithelium developmentdefinition[GO:0061180]  
1
  • Ortholog Curator
Mesoderm developmentdefinition[GO:0007498]  
1
  • PINC
Mineralocorticoid receptor signaling pathwaydefinition[GO:0031959] silver  
1
  • Ortholog Compara
Movement of cell or subcellular componentdefinition[GO:0006928]  
1
  • PINC
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • Ortholog Curator
Negative regulation of cell-cell adhesiondefinition[GO:0022408] silver  
1
  • Ortholog Compara
Negative regulation of DNA bindingdefinition[GO:0043392]  
1
  • Ortholog Curator
Negative regulation of heart contractiondefinition[GO:0045822] silver  
1
  • Ortholog Compara
Negative regulation of neuron apoptotic processdefinition[GO:0043524] silver  
1
  • Ortholog Compara
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • Ortholog Curator
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008] silver  
1
  • Ortholog Compara
Positive regulation of cell activationdefinition[GO:0050867] silver  
1
  • Ortholog Compara
Positive regulation of cell differentiationdefinition[GO:0045597] silver  
1
  • Ortholog Compara
Positive regulation of cell migrationdefinition[GO:0030335] silver  
1
  • Ortholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
1
  • Ortholog Compara
Positive regulation of cell-substrate adhesiondefinition[GO:0010811]  
1
  • BHF-UCL
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204] silver  
1
  • Ortholog Compara
Positive regulation of DNA bindingdefinition[GO:0043388] silver  
1
  • Ortholog Compara
Positive regulation of growth hormone receptor signaling pathwaydefinition[GO:0060399]  
1
  • Ortholog Curator
Positive regulation of inflammatory responsedefinition[GO:0050729] silver  
1
  • Ortholog Compara
Positive regulation of insulin secretiondefinition[GO:0032024] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-1 beta productiondefinition[GO:0032731] silver  
1
  • Ortholog Compara
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429] silver  
1
  • Ortholog Compara
Positive regulation of nitric-oxide synthase biosynthetic processdefinition[GO:0051770]  
1
  • Ortholog Curator
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
1
  • Ortholog Curator
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • Ortholog Curator
Positive regulation of phosphoprotein phosphatase activitydefinition[GO:0032516] silver  
1
  • Ortholog Compara
Positive regulation of protein import into nucleus, translocationdefinition[GO:0033160] silver  
1
  • Ortholog Compara
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091] silver  
1
  • Ortholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
1
  • Ortholog Compara
Positive regulation of tumor necrosis factor productiondefinition[GO:0032760]  
1
  • Ortholog Curator
Positive regulation of tyrosine phosphorylation of Stat3 proteindefinition[GO:0042517]  
1
  • Ortholog Curator
Positive regulation of tyrosine phosphorylation of Stat5 proteindefinition[GO:0042523]  
1
  • Ortholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
1
  • Ortholog Curator
Protein phosphorylationdefinition[GO:0006468]  
1
  • PINC
Regulation of apoptotic processdefinition[GO:0042981]  
1
  • RefGenome
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • RefGenome
Regulation of inflammatory responsedefinition[GO:0050727]  
1
  • BHF-UCL
Response to antibioticdefinition[GO:0046677]  
1
  • MGI
Response to hydroperoxidedefinition[GO:0033194] silver  
1
  • Ortholog Compara
Response to interleukin-12definition[GO:0070671]  
1
  • BHF-UCL
Response to lipopolysaccharidedefinition[GO:0032496]  
1
  • Ortholog Curator
Response to tumor necrosis factordefinition[GO:0034612]  
1
  • BHF-UCL
Signal transductiondefinition[GO:0007165]  
1
  • Ortholog Curator
STAT protein import into nucleusdefinition[GO:0007262]  
1
  • Ortholog Curator
Tumor necrosis factor-mediated signaling pathwaydefinition[GO:0033209]  
1
  • BHF-UCL
Tyrosine phosphorylation of STAT proteindefinition[GO:0007260]  
2
  • RefGenome
  • Ortholog Curator
Tyrosine phosphorylation of Stat1 proteindefinition[GO:0042508] silver  
1
  • Ortholog Compara
Tyrosine phosphorylation of Stat3 proteindefinition[GO:0042503] silver  
1
  • Ortholog Compara
Tyrosine phosphorylation of Stat5 proteindefinition[GO:0042506] silver  
1
  • Ortholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
2
  • PROSITE-ProRule
  • UniProtKB
It is regulated in the following manner
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.  
2
  • UniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adipocytokine signaling pathway  hsa04920+3717  
Chemokine signaling pathway  hsa04062+3717  
Cholinergic synapse  hsa04725+3717  
Herpes simplex infection  hsa05168+3717  
Influenza A  hsa05164+3717  
Jak-STAT signaling pathway  hsa04630+3717  
Leishmaniasis  hsa05140+3717  
Measles  hsa05162+3717  
Toxoplasmosis  hsa05145+3717  
Tuberculosis  hsa05152+3717  
According to Reactome, this protein belongs to the following pathways:
ERK1 activation  REACT_1391  
ERK2 activation  REACT_1183  
Factors involved in megakaryocyte development and platelet production  REACT_24970  
G beta:gamma signalling through PI3Kgamma  REACT_19290  
GPVI-mediated activation cascade  REACT_1695  
Growth hormone receptor signaling  REACT_111133  
Interferon gamma signaling  REACT_25078  
Interleukin receptor SHC signaling  REACT_23891  
Interleukin-3, 5 and GM-CSF signaling  REACT_23837  
Interleukin-6 signaling  REACT_27307  
Prolactin receptor signaling  REACT_115697  
Regulation of IFNG signaling  REACT_24980  
RMTs methylate histone arginines  REACT_264545  
Signaling by Leptin  REACT_169118  
Signaling by SCF-KIT  REACT_111040  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Chromatin regulator  definition   [KW-0156]
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Janus_kinase_2
GenomeRNAi: 3717
PRO: PR:O60674
Chemistry
GuidetoPHARMACOLOGY: 2048