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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1 854 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.  
4
  • CuratedUniProtKB
GO molecular function 
Acetylcholine receptor bindingdefinition[GO:0033130] silver  
  • IEAOrtholog Compara
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Growth hormone receptor bindingdefinition[GO:0005131]  
  • ISSOrtholog Curator
Heme bindingdefinition[GO:0020037]  
1
  • IDAUniProtKB
Histone bindingdefinition[GO:0042393]  
1
  • IDAUniProtKB
Histone kinase activity (H3-Y41 specific)definition[GO:0035401]  
1
  • IDAUniProtKB
Insulin receptor substrate bindingdefinition[GO:0043560] silver  
  • IEAOrtholog Compara
Interleukin-12 receptor bindingdefinition[GO:0005143]  
  • ISSOrtholog Curator
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
  • IEAEC 2 GO
Peptide hormone receptor bindingdefinition[GO:0051428] silver  
  • IEAOrtholog Compara
Phosphatidylinositol 3-kinase bindingdefinition[GO:0043548] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
8
  • IPIIntAct
  • IPIUniProtKB
Protein C-terminus bindingdefinition[GO:0008022] silver  
  • IEAOrtholog Compara
Protein kinase activitydefinition[GO:0004672]  
1
  • NASPINC
Protein kinase bindingdefinition[GO:0019901]  
1
  • IDABHF-UCL
Protein tyrosine kinase activitydefinition[GO:0004713]  
  • ISSOrtholog Curator
Receptor bindingdefinition[GO:0005102]  
1
  • IPIUniProtKB
SH2 domain bindingdefinition[GO:0042169]  
1
  • IPIUniProtKB
Type 1 angiotensin receptor bindingdefinition[GO:0031702] silver  
  • IEAOrtholog Compara
GO biological process 
Actin filament polymerizationdefinition[GO:0030041]  
1
  • NASBHF-UCL
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919]  
  • ISSOrtholog Curator
Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathwaydefinition[GO:0097296]  
  • ISSOrtholog Curator
Activation of JAK2 kinase activitydefinition[GO:0042977]  
  • ISSOrtholog Curator
Activation of MAPKK activitydefinition[GO:0000186] silver  
  • IEAOrtholog Compara
Apoptotic processdefinition[GO:0006915]  
  • ISSOrtholog Curator
Axon regenerationdefinition[GO:0031103] silver  
  • IEAOrtholog Compara
Cell differentiationdefinition[GO:0030154]  
  • ISSOrtholog Curator
Cellular component movementdefinition[GO:0006928]  
1
  • TASPINC
Cytokine-mediated signaling pathwaydefinition[GO:0019221]  
1
  • IDABHF-UCL
  • ISSOrtholog Curator
Enzyme linked receptor protein signaling pathwaydefinition[GO:0007167]  
  • ISSOrtholog Curator
Erythrocyte differentiationdefinition[GO:0030218]  
  • ISSOrtholog Curator
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191]  
  • ISSOrtholog Curator
G-protein coupled receptor signaling pathwaydefinition[GO:0007186] silver  
  • IEAOrtholog Compara
Growth hormone receptor signaling pathwaydefinition[GO:0060396]  
1
  • IDABHF-UCL
Histone H3-Y41 phosphorylationdefinition[GO:0035409]  
1
  • IDAUniProtKB
Hormone-mediated signaling pathwaydefinition[GO:0009755] silver  
  • IEAOrtholog Compara
Host programmed cell death induced by symbiontdefinition[GO:0034050] silver  
  • IEAOrtholog Compara
Interleukin-12-mediated signaling pathwaydefinition[GO:0035722]  
1
  • IDABHF-UCL
Intracellular signal transductiondefinition[GO:0035556]  
  • ISSOrtholog Curator
Intrinsic apoptotic signaling pathway in response to oxidative stressdefinition[GO:0008631] silver  
  • IEAOrtholog Compara
JAK-STAT cascadedefinition[GO:0007259]  
1
  • TASPINC
JAK-STAT cascade involved in growth hormone signaling pathwaydefinition[GO:0060397]  
  • ISSOrtholog Curator
Mammary gland epithelium developmentdefinition[GO:0061180]  
  • ISSOrtholog Curator
Mesoderm developmentdefinition[GO:0007498]  
1
  • TASPINC
Mineralocorticoid receptor signaling pathwaydefinition[GO:0031959] silver  
  • IEAOrtholog Compara
Negative regulation of cell proliferationdefinition[GO:0008285]  
  • ISSOrtholog Curator
Negative regulation of cell-cell adhesiondefinition[GO:0022408] silver  
  • IEAOrtholog Compara
Negative regulation of DNA bindingdefinition[GO:0043392]  
  • ISSOrtholog Curator
Negative regulation of heart contractiondefinition[GO:0045822] silver  
  • IEAOrtholog Compara
Negative regulation of neuron apoptotic processdefinition[GO:0043524] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
  • ISSOrtholog Curator
Platelet-derived growth factor receptor signaling pathwaydefinition[GO:0048008] silver  
  • IEAOrtholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235] silver  
  • IEAOrtholog Compara
Positive regulation of cell activationdefinition[GO:0050867] silver  
  • IEAOrtholog Compara
Positive regulation of cell differentiationdefinition[GO:0045597] silver  
  • IEAOrtholog Compara
Positive regulation of cell migrationdefinition[GO:0030335] silver  
  • IEAOrtholog Compara
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
  • IEAOrtholog Compara
Positive regulation of cell-substrate adhesiondefinition[GO:0010811]  
1
  • IDABHF-UCL
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204] silver  
  • IEAOrtholog Compara
Positive regulation of DNA bindingdefinition[GO:0043388] silver  
  • IEAOrtholog Compara
Positive regulation of growth hormone receptor signaling pathwaydefinition[GO:0060399]  
  • ISSOrtholog Curator
Positive regulation of inflammatory responsedefinition[GO:0050729] silver  
  • IEAOrtholog Compara
Positive regulation of insulin secretiondefinition[GO:0032024] silver  
  • IEAOrtholog Compara
Positive regulation of interleukin-1 beta productiondefinition[GO:0032731] silver  
  • IEAOrtholog Compara
Positive regulation of nitric oxide biosynthetic processdefinition[GO:0045429] silver  
  • IEAOrtholog Compara
Positive regulation of nitric-oxide synthase biosynthetic processdefinition[GO:0051770]  
  • ISSOrtholog Curator
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731]  
  • ISSOrtholog Curator
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
  • ISSOrtholog Curator
Positive regulation of phosphoprotein phosphatase activitydefinition[GO:0032516] silver  
  • IEAOrtholog Compara
Positive regulation of protein import into nucleus, translocationdefinition[GO:0033160] silver  
  • IEAOrtholog Compara
Positive regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051091] silver  
  • IEAOrtholog Compara
Positive regulation of tumor necrosis factor productiondefinition[GO:0032760]  
  • ISSOrtholog Curator
Positive regulation of tyrosine phosphorylation of Stat3 proteindefinition[GO:0042517]  
  • ISSOrtholog Curator
Positive regulation of tyrosine phosphorylation of Stat5 proteindefinition[GO:0042523]  
  • ISSOrtholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
  • ISSOrtholog Curator
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of inflammatory responsedefinition[GO:0050727]  
1
  • IDABHF-UCL
Response to antibioticdefinition[GO:0046677]  
1
  • IDAMGI
Response to hydroperoxidedefinition[GO:0033194] silver  
  • IEAOrtholog Compara
Response to interleukin-12definition[GO:0070671]  
1
  • IDABHF-UCL
Response to lipopolysaccharidedefinition[GO:0032496]  
  • ISSOrtholog Curator
Response to tumor necrosis factordefinition[GO:0034612]  
1
  • IDABHF-UCL
Signal transductiondefinition[GO:0007165]  
  • ISSOrtholog Curator
STAT protein import into nucleusdefinition[GO:0007262]  
  • ISSOrtholog Curator
Tumor necrosis factor-mediated signaling pathwaydefinition[GO:0033209]  
1
  • IDABHF-UCL
Tyrosine phosphorylation of STAT proteindefinition[GO:0007260]  
  • ISSOrtholog Curator
Tyrosine phosphorylation of Stat1 proteindefinition[GO:0042508] silver  
  • IEAOrtholog Compara
Tyrosine phosphorylation of Stat3 proteindefinition[GO:0042503] silver  
  • IEAOrtholog Compara
Tyrosine phosphorylation of Stat5 proteindefinition[GO:0042506] silver  
  • IEAOrtholog 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.  
  • CuratedUniProtKB
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.  
1
  • CuratedUniProtKB
 
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:
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

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