JAK2
Janus kinase 2 | JTK10

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]

Member of: DE-4 DE-4.12 Developmental clusters: GC7
Biological processes 186 terms
ATP binding (GO:0005524)SH2 domain binding (GO:0042169)acetylcholine receptor binding (GO:0033130)actin filament polymerization (GO:0030041)activation of Janus kinase activity (GO:0042976)apoptotic process (GO:0006915)axon regeneration (GO:0031103)caveola (GO:0005901)caveola (GO:0005901)cell adhesion (GO:0007155)cell differentiation (GO:0030154)cell surface receptor signaling pathway via JAK-STAT (GO:0007259)cell surface receptor signaling pathway via JAK-STAT (GO:0007259)cell surface receptor signaling pathway via JAK-STAT (GO:0007259)cell surface receptor signaling pathway via JAK-STAT (GO:0007259)chromatin (GO:0000785)chromatin remodeling (GO:0006338)ciliary neurotrophic factor-mediated signaling pathway (GO:0070120)collagen-activated signaling pathway (GO:0038065)cytokine-mediated signaling pathway (GO:0019221)cytokine-mediated signaling pathway (GO:0019221)cytokine-mediated signaling pathway (GO:0019221)cytokine-mediated signaling pathway (GO:0019221)cytokine-mediated signaling pathway (GO:0019221)cytoplasm (GO:0005737)cytoplasm (GO:0005737)cytoplasmic side of plasma membrane (GO:0009898)cytoplasmic side of plasma membrane (GO:0009898)cytosol (GO:0005829)cytosol (GO:0005829)cytosol (GO:0005829)defense response to symbiont (GO:0140546)endomembrane system (GO:0012505)endosome (GO:0005768)endosome lumen (GO:0031904)enzyme-linked receptor protein signaling pathway (GO:0007167)erythrocyte differentiation (GO:0030218)erythrocyte differentiation (GO:0030218)erythrocyte differentiation (GO:0030218)erythropoietin-mediated signaling pathway (GO:0038162)euchromatin (GO:0000791)extrinsic apoptotic signaling pathway (GO:0097191)extrinsic component of cytoplasmic side of plasma membrane (GO:0031234)extrinsic component of cytoplasmic side of plasma membrane (GO:0031234)extrinsic component of cytoplasmic side of plasma membrane (GO:0031234)extrinsic component of plasma membrane (GO:0019897)glutamatergic synapse (GO:0098978)granulocyte-macrophage colony-stimulating factor signaling pathway (GO:0038157)growth hormone receptor binding (GO:0005131)growth hormone receptor binding (GO:0005131)growth hormone receptor binding (GO:0005131)growth hormone receptor signaling pathway (GO:0060396)growth hormone receptor signaling pathway via JAK-STAT (GO:0060397)growth hormone receptor signaling pathway via JAK-STAT (GO:0060397)growth hormone receptor signaling pathway via JAK-STAT (GO:0060397)growth hormone receptor signaling pathway via JAK-STAT (GO:0060397)heme binding (GO:0020037)histone H3Y41 kinase activity (GO:0035401)histone binding (GO:0042393)hormone-mediated signaling pathway (GO:0009755)identical protein binding (GO:0042802)immune system process (GO:0002376)insulin receptor substrate binding (GO:0043560)interleukin-12 receptor binding (GO:0005143)interleukin-12 receptor binding (GO:0005143)interleukin-12-mediated signaling pathway (GO:0035722)interleukin-23-mediated signaling pathway (GO:0038155)interleukin-3-mediated signaling pathway (GO:0038156)interleukin-35-mediated signaling pathway (GO:0070757)interleukin-5-mediated signaling pathway (GO:0038043)interleukin-5-mediated signaling pathway (GO:0038043)interleukin-6-mediated signaling pathway (GO:0070102)intracellular signal transduction (GO:0035556)intracellular signal transduction (GO:0035556)intracellular signal transduction (GO:0035556)intracellular signal transduction (GO:0035556)intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631)leukemia inhibitory factor signaling pathway (GO:0048861)lipopolysaccharide-mediated signaling pathway (GO:0031663)lipopolysaccharide-mediated signaling pathway (GO:0031663)mammary gland epithelium development (GO:0061180)membrane (GO:0016020)membrane raft (GO:0045121)membrane raft (GO:0045121)mesoderm development (GO:0007498)microglial cell activation (GO:0001774)microglial cell activation (GO:0001774)modulation of chemical synaptic transmission (GO:0050804)negative regulation of apoptotic process (GO:0043066)negative regulation of cardiac muscle cell apoptotic process (GO:0010667)negative regulation of cell population proliferation (GO:0008285)negative regulation of cell-cell adhesion (GO:0022408)negative regulation of cytokine production involved in inflammatory response (GO:1900016)negative regulation of cytokine production involved in inflammatory response (GO:1900016)negative regulation of neuron apoptotic process (GO:0043524)negative regulation of protein localization to chromatin (GO:0120186)non-membrane spanning protein tyrosine kinase activity (GO:0004715)non-membrane spanning protein tyrosine kinase activity (GO:0004715)non-membrane spanning protein tyrosine kinase activity (GO:0004715)non-membrane spanning protein tyrosine kinase activity (GO:0004715)nuclear receptor-mediated mineralocorticoid signaling pathway (GO:0031959)nucleoplasm (GO:0005654)nucleoplasm (GO:0005654)nucleus (GO:0005634)nucleus (GO:0005634)oncostatin-M-mediated signaling pathway (GO:0038165)peptide hormone receptor binding (GO:0051428)phosphatidylinositol 3-kinase binding (GO:0043548)plasma membrane (GO:0005886)platelet-derived growth factor receptor signaling pathway (GO:0048008)positive regulation of MAPK cascade (GO:0043410)positive regulation of MHC class II biosynthetic process (GO:0045348)positive regulation of MHC class II biosynthetic process (GO:0045348)positive regulation of SMAD protein signal transduction (GO:0060391)positive regulation of T cell proliferation (GO:0042102)positive regulation of apoptotic process (GO:0043065)positive regulation of cell activation (GO:0050867)positive regulation of cell adhesion (GO:0045785)positive regulation of cell differentiation (GO:0045597)positive regulation of cell migration (GO:0030335)positive regulation of cell population proliferation (GO:0008284)positive regulation of cell-substrate adhesion (GO:0010811)positive regulation of cold-induced thermogenesis (GO:0120162)positive regulation of cold-induced thermogenesis (GO:0120162)positive regulation of cytokine production (GO:0001819)positive regulation of cytosolic calcium ion concentration (GO:0007204)positive regulation of epithelial cell apoptotic process (GO:1904037)positive regulation of growth factor dependent skeletal muscle satellite cell proliferation (GO:1902728)positive regulation of growth hormone receptor signaling pathway (GO:0060399)positive regulation of growth hormone receptor signaling pathway (GO:0060399)positive regulation of insulin secretion (GO:0032024)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of interleukin-1 beta production (GO:0032731)positive regulation of intracellular signal transduction (GO:1902533)positive regulation of leukocyte proliferation (GO:0070665)positive regulation of nitric oxide biosynthetic process (GO:0045429)positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)positive regulation of platelet activation (GO:0010572)positive regulation of platelet aggregation (GO:1901731)positive regulation of protein import into nucleus (GO:0042307)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of transcription by RNA polymerase II (GO:0045944)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of tumor necrosis factor production (GO:0032760)positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531)positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707)post-embryonic hemopoiesis (GO:0035166)post-translational protein modification (GO:0043687)postsynapse (GO:0098794)protein autophosphorylation (GO:0046777)protein binding (GO:0005515)protein kinase activity (GO:0004672)protein kinase activity (GO:0004672)protein kinase binding (GO:0019901)protein tyrosine kinase activity (GO:0004713)protein tyrosine kinase activity (GO:0004713)protein tyrosine kinase activity (GO:0004713)protein tyrosine kinase activity (GO:0004713)protein tyrosine kinase activity (GO:0004713)regulation of alpha-beta T cell activation (GO:0046634)regulation of apoptotic process (GO:0042981)regulation of cell-cell adhesion (GO:0022407)regulation of inflammatory response (GO:0050727)regulation of nitric oxide biosynthetic process (GO:0045428)regulation of nitric oxide biosynthetic process (GO:0045428)regulation of postsynapse to nucleus signaling pathway (GO:1905539)regulation of receptor signaling pathway via JAK-STAT (GO:0046425)regulation of receptor signaling pathway via JAK-STAT (GO:0046425)response to antibiotic (GO:0046677)response to hydroperoxide (GO:0033194)response to interleukin-12 (GO:0070671)response to oxidative stress (GO:0006979)response to tumor necrosis factor (GO:0034612)signal transduction (GO:0007165)signal transduction (GO:0007165)signaling receptor activator activity (GO:0030546)signaling receptor activator activity (GO:0030546)signaling receptor binding (GO:0005102)signaling receptor binding (GO:0005102)thrombopoietin-mediated signaling pathway (GO:0038163)tumor necrosis factor-mediated signaling pathway (GO:0033209)type 1 angiotensin receptor binding (GO:0031702)type II interferon-mediated signaling pathway (GO:0060333)type II interferon-mediated signaling pathway (GO:0060333)
Expression (TPM)
JAK2 — as a Regulated Gene

TFs regulating JAK2 0 TFs

Transcription factors with Perturb-seq knockdown data for JAK2. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = JAK2 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to JAK2

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of JAK2, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr9:4,740,523–4,742,116 244.0 kb Distal (>10kb) Multiome 942
chr9:4,762,590–4,763,629 221.9 kb Distal (>10kb) Multiome HiCAR 504
chr9:4,792,132–4,794,058 192.5 kb Distal (>10kb) Multiome HiCAR 871
chr9:4,984,214–4,986,401 160 bp At TSS Multiome 981
chr9:4,987,794–4,988,238 2.5 kb Proximal (<10kb) 271
chr9:4,994,255–4,994,774 9.0 kb Proximal (<10kb) 68

Genome Browser

Genomic view of the JAK2 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr9:4,730,523 – 5,004,774
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq