Names & Taxonomy

Uniprot ID:
O60674
Entry Name:
JAK2_HUMAN
Status:
reviewed
Protein Names:
Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2)
Gene Names:
JAK2
Gene Names Primary:
JAK2
Organism:
Homo sapiens (Human)

Structure

Length:
1132
Sequence:
MGMACLTMTEMEGTSTSSIYQNGDISGNANSMKQIDPVLQVYLYHSLGKSEADYLTFPSGEYVAEEICIAASKACGITPVYHNMFALMSETERIWYPPNHVFHIDESTRHNVLYRIRFYFPRWYCSGSNRAYRHGISRGAEAPLLDDFVMSYLFAQWRHDFVHGWIKVPVTHETQEECLGMAVLDMMRIAKENDQTPLAIYNSISYKTFLPKCIRAKIQDYHILTRKRIRYRFRRFIQQFSQCKATARNLKLKYLINLETLQSAFYTEKFEVKEPGSGPSGEEIFATIIITGNGGIQWSRGKHKESETLTEQDLQLYCDFPNIIDVSIKQANQEGSNESRVVTIHKQDGKNLEIELSSLREALSFVSLIDGYYRLTADAHHYLCKEVAPPAVLENIQSNCHGPISMDFAISKLKKAGNQTGLYVLRCSPKDFNKYFLTFAVERENVIEYKHCLITKNENEEYNLSGTKKNFSSLKDLLNCYQMETVRSDNIIFQFTKCCPPKPKDKSNLLVFRTNGVSDVPTSPTLQRPTHMNQMVFHKIRNEDLIFNESLGQGTFTKIFKGVRREVGDYGQLHETEVLLKVLDKAHRNYSESFFEAASMMSKLSHKHLVLNYGVCVCGDENILVQEFVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEENTLIHGNVCAKNILLIREEDRKTGNPPFIKLSDPGISITVLPKDILQERIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGALGFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDLALRVDQIRDNMAG
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Endomembrane system

Function

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 (PubMed:7615558). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263). 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 (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). 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 (PubMed:19783980).
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 976 976 Proton acceptor.
Cross Reference Drug Bank:
DB08877 DB08895
Gene Ontology Go:
caveola
cytoplasm
cytoskeleton
cytosol
endosome lumen
extrinsic component of cytoplasmic side of plasma membrane
membrane raft
nuclear matrix
nucleoplasm
nucleus
ATP binding
growth hormone receptor binding
heme binding
histone binding
histone kinase activity (H3-Y41 specific)
interleukin-12 receptor binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein tyrosine kinase activity
receptor binding
SH2 domain binding
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 JAK2 kinase activity
activation of MAPKK activity
adaptive immune response
apoptotic process
axon guidance
axon regeneration
blood coagulation
cell differentiation
cell migration
chromatin organization
cytokine-mediated signaling pathway
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
erythrocyte differentiation
extrinsic apoptotic signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
G-protein coupled receptor signaling pathway
growth hormone receptor signaling pathway
histone H3-Y41 phosphorylation
innate immune response
insulin receptor signaling pathway
interferon-gamma-mediated signaling pathway
interleukin-12-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
movement of cell or subcellular component
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
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
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 proliferation
positive regulation of cell-substrate adhesion
positive regulation of cytosolic calcium ion concentration
positive regulation of DNA binding
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 protein import into nucleus, translocation
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of tumor necrosis factor production
positive regulation of tyrosine phosphorylation of Stat3 protein
positive regulation of tyrosine phosphorylation of Stat5 protein
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of apoptotic process
regulation of cell proliferation
regulation of inflammatory response
regulation of interferon-gamma-mediated signaling pathway
response to antibiotic
response to hydroperoxide
response to interleukin-12
response to lipopolysaccharide
response to tumor necrosis factor
signal transduction
small GTPase mediated signal transduction
STAT protein import into nucleus
tumor necrosis factor-mediated signaling pathway
tyrosine phosphorylation of STAT protein
tyrosine phosphorylation of Stat1 protein
tyrosine phosphorylation of Stat3 protein
tyrosine phosphorylation of Stat5 protein
vascular endothelial growth factor receptor signaling pathway
Gene Ontology 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 JAK2 kinase activity
activation of MAPKK activity
adaptive immune response
apoptotic process
axon guidance
axon regeneration
blood coagulation
cell differentiation
cell migration
chromatin organization
cytokine-mediated signaling pathway
enzyme linked receptor protein signaling pathway
epidermal growth factor receptor signaling pathway
erythrocyte differentiation
extrinsic apoptotic signaling pathway
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
G-protein coupled receptor signaling pathway
growth hormone receptor signaling pathway
histone H3-Y41 phosphorylation
innate immune response
insulin receptor signaling pathway
interferon-gamma-mediated signaling pathway
interleukin-12-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
movement of cell or subcellular component
negative regulation of cardiac muscle cell apoptotic process
negative regulation of cell-cell adhesion
negative regulation of cell proliferation
negative regulation of DNA binding
negative regulation of heart contraction
negative regulation of neuron apoptotic process
neurotrophin TRK receptor signaling pathway
peptidyl-tyrosine autophosphorylation
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 proliferation
positive regulation of cell-substrate adhesion
positive regulation of cytosolic calcium ion concentration
positive regulation of DNA binding
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 protein import into nucleus, translocation
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of tumor necrosis factor production
positive regulation of tyrosine phosphorylation of Stat3 protein
positive regulation of tyrosine phosphorylation of Stat5 protein
protein autophosphorylation
protein phosphorylation
Ras protein signal transduction
regulation of apoptotic process
regulation of cell proliferation
regulation of inflammatory response
regulation of interferon-gamma-mediated signaling pathway
response to antibiotic
response to hydroperoxide
response to interleukin-12
response to lipopolysaccharide
response to tumor necrosis factor
signal transduction
small GTPase mediated signal transduction
STAT protein import into nucleus
tumor necrosis factor-mediated signaling pathway
tyrosine phosphorylation of Stat1 protein
tyrosine phosphorylation of Stat3 protein
tyrosine phosphorylation of Stat5 protein
tyrosine phosphorylation of STAT protein
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
ATP binding
growth hormone receptor binding
heme binding
histone binding
histone kinase activity (H3-Y41 specific)
interleukin-12 receptor binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein tyrosine kinase activity
receptor binding
SH2 domain binding
Gene Ontology Cellular Component:
caveola
cytoplasm
cytoskeleton
cytosol
endosome lumen
extrinsic component of cytoplasmic side of plasma membrane
membrane raft
nuclear matrix
nucleoplasm
nucleus
Keywords:
3D-structure
ATP-binding
Adaptive immunity
Chromatin regulator
Chromosomal rearrangement
Complete proteome
Cytoplasm
Disease mutation
Immunity
Innate immunity
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Proto-oncogene
Reference proteome
Repeat
SH2 domain
Transferase
Tyrosine-protein kinase
Interacts With:
P32927; P40238; P16333; P18031

Publication

PubMed ID:
9618263 9446644 9326218 15164053 7615558 7673114 10531356 10899310 12023369 15805263 16034466 16091753 16769584 16424865 19783980 21036157 20098430 21423214 16456223 19290934 16174768 15781101 16325696 15793561 15858187 16707754 16247455 16603627 17267906 17344846 22397670