The JAK2 gene and its putative association with human ageing

Cell Types

Melanocyte

Cell Lines

Primary cell

Cancer Cell?

No

Method

Knockdown

Type of senescence

Unclear

Senescence Effect

Induces

Primary Reference

Wang et al. (2015) Interferon-γ induces senescence in normal human melanocytes. PLoS One 9(3)e93232 (PubMed)

HGNC symbol

JAK2

Aliases

JTK10

Common name

Janus kinase 2

Entrez Id

3717

Description

This gene encodes a non-receptor tyrosine kinase that plays a central role in cytokine and growth factor signalling. The primary isoform of this protein has an N-terminal FERM domain that is required for erythropoietin receptor association, an SH2 domain that binds STAT transcription factors, a pseudokinase domain and a C-terminal tyrosine kinase domain. Cytokine binding induces autophosphorylation and activation of this kinase. This kinase then recruits and phosphorylates signal transducer and activator of transcription (STAT) proteins. Growth factors like TGF-beta 1 also induce phosphorylation and activation of this kinase and translocation of downstream STAT proteins to the nucleus where they influence gene transcription. Mutations in this gene are associated with numerous inflammatory diseases and malignancies. This gene is a downstream target of the pleiotropic cytokine IL6 that is produced by B cells, T cells, dendritic cells and macrophages to produce an immune response or inflammation. Disregulation of the IL6/JAK2/STAT3 signalling pathways produces increased cellular proliferation and myeloproliferative neoplasms of hematopoietic stem cells. A nonsynonymous mutation in the pseudokinase domain of this gene disrupts the domains inhibitory effect and results in constitutive tyrosine phosphorylation activity and hypersensitivity to cytokine signalling. This gene and the IL6/JAK2/STAT3 signalling pathway is a therapeutic target for the treatment of excessive inflammatory responses to viral infections. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020].

Gene Ontology

Process:

GO:6468; protein phosphorylation
GO:16310; phosphorylation
GO:35556; intracellular signal transduction
GO:18108; peptidyl-tyrosine phosphorylation
GO:6325; chromatin organization
GO:19221; cytokine-mediated signaling pathway
GO:7165; signal transduction
GO:2376; immune system process
GO:45087; innate immune response
GO:2250; adaptive immune response
GO:46777; protein autophosphorylation
GO:30218; erythrocyte differentiation
GO:30154; cell differentiation
GO:42981; regulation of apoptotic process
GO:14068; positive regulation of phosphatidylinositol 3-kinase signaling
GO:50731; positive regulation of peptidyl-tyrosine phosphorylation
GO:32496; response to lipopolysaccharide
GO:32760; positive regulation of tumor necrosis factor production
GO:51770; positive regulation of nitric-oxide synthase biosynthetic process
GO:120162; positive regulation of cold-induced thermogenesis
GO:7259; receptor signaling pathway via JAK-STAT
GO:60396; growth hormone receptor signaling pathway
GO:34612; response to tumor necrosis factor
GO:33209; tumor necrosis factor-mediated signaling pathway
GO:8285; negative regulation of cell population proliferation
GO:7498; mesoderm development
GO:97191; extrinsic apoptotic signaling pathway
GO:32731; positive regulation of interleukin-1 beta production
GO:43392; negative regulation of DNA binding
GO:1901731; positive regulation of platelet aggregation
GO:10572; positive regulation of platelet activation
GO:46677; response to antibiotic
GO:60391; positive regulation of SMAD protein signal transduction
GO:1774; microglial cell activation
GO:6915; apoptotic process
GO:6919; activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:6979; response to oxidative stress
GO:7167; enzyme linked receptor protein signaling pathway
GO:7186; G protein-coupled receptor signaling pathway
GO:7204; positive regulation of cytosolic calcium ion concentration
GO:7260; tyrosine phosphorylation of STAT protein
GO:8284; positive regulation of cell population proliferation
GO:8631; intrinsic apoptotic signaling pathway in response to oxidative stress
GO:9755; hormone-mediated signaling pathway
GO:10667; negative regulation of cardiac muscle cell apoptotic process
GO:10811; positive regulation of cell-substrate adhesion
GO:14070; response to organic cyclic compound
GO:14075; response to amine
GO:22408; negative regulation of cell-cell adhesion
GO:30041; actin filament polymerization
GO:30099; myeloid cell differentiation
GO:30335; positive regulation of cell migration
GO:31103; axon regeneration
GO:31959; mineralocorticoid receptor signaling pathway
GO:32024; positive regulation of insulin secretion
GO:32516; positive regulation of phosphoprotein phosphatase activity
GO:32729; positive regulation of interferon-gamma production
GO:32819; positive regulation of natural killer cell proliferation
GO:33194; response to hydroperoxide
GO:34050; programmed cell death induced by symbiont
GO:35166; post-embryonic hemopoiesis
GO:35409; histone H3-Y41 phosphorylation
GO:35722; interleukin-12-mediated signaling pathway
GO:36016; cellular response to interleukin-3
GO:38065; collagen-activated signaling pathway
GO:38157; granulocyte-macrophage colony-stimulating factor signaling pathway
GO:42102; positive regulation of T cell proliferation
GO:42307; positive regulation of protein import into nucleus
GO:42531; positive regulation of tyrosine phosphorylation of STAT protein
GO:42976; activation of Janus kinase activity
GO:43065; positive regulation of apoptotic process
GO:43066; negative regulation of apoptotic process
GO:43388; positive regulation of DNA binding
GO:43410; positive regulation of MAPK cascade
GO:43524; negative regulation of neuron apoptotic process
GO:45348; positive regulation of MHC class II biosynthetic process
GO:45428; regulation of nitric oxide biosynthetic process
GO:45429; positive regulation of nitric oxide biosynthetic process
GO:45597; positive regulation of cell differentiation
GO:45822; negative regulation of heart contraction
GO:45944; positive regulation of transcription by RNA polymerase II
GO:46425; regulation of receptor signaling pathway via JAK-STAT
GO:46427; positive regulation of receptor signaling pathway via JAK-STAT
GO:48008; platelet-derived growth factor receptor signaling pathway
GO:50727; regulation of inflammatory response
GO:50729; positive regulation of inflammatory response
GO:50804; modulation of chemical synaptic transmission
GO:50867; positive regulation of cell activation
GO:51091; positive regulation of DNA-binding transcription factor activity
GO:51142; positive regulation of NK T cell proliferation
GO:60333; interferon-gamma-mediated signaling pathway
GO:60397; growth hormone receptor signaling pathway via JAK-STAT
GO:60399; positive regulation of growth hormone receptor signaling pathway
GO:60548; negative regulation of cell death
GO:61180; mammary gland epithelium development
GO:70102; interleukin-6-mediated signaling pathway
GO:70665; positive regulation of leukocyte proliferation
GO:70671; response to interleukin-12
GO:70757; interleukin-35-mediated signaling pathway
GO:71222; cellular response to lipopolysaccharide
GO:71549; cellular response to dexamethasone stimulus
GO:97296; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:99527; postsynapse to nucleus signaling pathway
GO:1902728; positive regulation of growth factor dependent skeletal muscle satellite cell proliferation
GO:1904037; positive regulation of epithelial cell apoptotic process
GO:1904707; positive regulation of vascular associated smooth muscle cell proliferation
GO:2000273; positive regulation of signaling receptor activity
GO:2001235; positive regulation of apoptotic signaling pathway
GO:6955; immune response
GO:32740; positive regulation of interleukin-17 production
GO:98586; cellular response to virus
GO:2000318; positive regulation of T-helper 17 type immune response

Cellular component:

GO:5737; cytoplasm
GO:16020; membrane
GO:5654; nucleoplasm
GO:5886; plasma membrane
GO:5925; focal adhesion
GO:12505; endomembrane system
GO:5856; cytoskeleton
GO:5634; nucleus
GO:5829; cytosol
GO:31904; endosome lumen
GO:30526; granulocyte macrophage colony-stimulating factor receptor complex
GO:791; euchromatin
GO:5730; nucleolus
GO:5901; caveola
GO:45121; membrane raft
GO:98794; postsynapse
GO:98978; glutamatergic synapse
GO:42022; interleukin-12 receptor complex
GO:72536; interleukin-23 receptor complex

Function:

GO:166; nucleotide binding
GO:4672; protein kinase activity
GO:4712; protein serine/threonine/tyrosine kinase activity
GO:5524; ATP binding
GO:16301; kinase activity
GO:16740; transferase activity
GO:4713; protein tyrosine kinase activity
GO:4715; non-membrane spanning protein tyrosine kinase activity
GO:42393; histone binding
GO:46872; metal ion binding
GO:5515; protein binding
GO:5102; signaling receptor binding
GO:42802; identical protein binding
GO:20037; heme binding
GO:5131; growth hormone receptor binding
GO:42169; SH2 domain binding
GO:19901; protein kinase binding
GO:5143; interleukin-12 receptor binding
GO:8022; protein C-terminus binding
GO:31702; type 1 angiotensin receptor binding
GO:33130; acetylcholine receptor binding
GO:35401; histone kinase activity (H3-Y41 specific)
GO:43548; phosphatidylinositol 3-kinase binding
GO:43560; insulin receptor substrate binding
GO:51428; peptide hormone receptor binding

Hide GO terms

Danio rerio

jak2b

Mus musculus

Jak2

Rattus norvegicus

Jak2

GenAge human genes