JAK2 [The Human Chemical-Genetic Interaction Map Project]

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======= JAK2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: JAK2
  * **<color #00a2e8>Official Name</color>**: Janus kinase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3717|3717]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O60674|O60674]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=JAK2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20JAK2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/147796|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene product is a protein tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. It has been found to be constituitively associated with the prolactin receptor and is required for responses to gamma interferon. Mice that do not express an active protein for this gene exhibit embryonic lethality associated with the absence of definitive erythropoiesis. [provided by RefSeq, Jul 2008]. COMPLETENESS: complete on the 3' end. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). 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). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase|
|SH2|
|Pkinase Tyr|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|histone-tyrosine phosphorylation|
|mineralocorticoid receptor signaling pathway|
|histone kinase activity (H3-Y41 specific)|
|histone H3-Y41 phosphorylation|
|positive regulation of skeletal muscle satellite cell proliferation|
|positive regulation of growth factor dependent skeletal muscle satellite cell proliferation|
|positive regulation of skeletal muscle cell proliferation|
|positive regulation of growth hormone receptor signaling pathway|
|activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway|
|regulation of growth hormone receptor signaling pathway|
|interleukin-12 receptor binding|
|activation of Janus kinase activity|
|regulation of interleukin-1 biosynthetic process|
|type 1 angiotensin receptor binding|
|positive regulation of interleukin-1 biosynthetic process|
|positive regulation of interleukin-1 beta biosynthetic process|
|regulation of interleukin-1 beta biosynthetic process|
|corticosteroid receptor signaling pathway|
|interleukin-23-mediated signaling pathway|
|growth hormone receptor binding|
|tyrosine phosphorylation of STAT protein|
|postsynapse to nucleus signaling pathway|
|positive regulation of MHC class II biosynthetic process|
|peptide hormone receptor binding|
|interleukin-35-mediated signaling pathway|
|insulin receptor substrate binding|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway|
|interleukin-27-mediated signaling pathway|
|regulation of skeletal muscle satellite cell proliferation|
|positive regulation of receptor biosynthetic process|
|growth hormone receptor signaling pathway via JAK-STAT|
|regulation of MHC class II biosynthetic process|
|regulation of skeletal muscle cell proliferation|
|acetylcholine receptor binding|
|positive regulation of nitric-oxide synthase biosynthetic process|
|intrinsic apoptotic signaling pathway in response to oxidative stress|
|interleukin-6-mediated signaling pathway|
|endosome lumen|
|regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway|
|regulation of nitric-oxide synthase biosynthetic process|
|growth hormone receptor signaling pathway|
|cell death in response to oxidative stress|
|positive regulation of tumor necrosis factor biosynthetic process|
|response to hydroperoxide|
|phosphatidylinositol 3-kinase binding|
|cellular response to growth hormone stimulus|
|positive regulation of phosphoprotein phosphatase activity|
|negative regulation of cardiac muscle cell apoptotic process|
|axon regeneration|
|regulation of receptor biosynthetic process|
|negative regulation of heart contraction|
|regulation of response to interferon-gamma|
|negative regulation of striated muscle cell apoptotic process|
|regulation of interferon-gamma-mediated signaling pathway|
|histone phosphorylation|
|neuron projection regeneration|
|regulation of tumor necrosis factor biosynthetic process|
|microglial cell activation|
|leukocyte activation involved in inflammatory response|
|actin filament polymerization|
|cellular response to interleukin-6|
|positive regulation of epithelial cell apoptotic process|
|positive regulation of vascular smooth muscle cell proliferation|
|negative regulation of blood circulation|
|platelet-derived growth factor receptor signaling pathway|
|response to growth hormone|
|positive regulation of phosphatase activity|
|SH2 domain binding|
|response to interleukin-6|
|regulation of cardiac muscle cell apoptotic process|
|negative regulation of muscle cell apoptotic process|
|glial cell activation|
|receptor signaling pathway via JAK-STAT|
|regulation of striated muscle cell apoptotic process|
|postsynaptic signal transduction|
|positive regulation of nitric oxide biosynthetic process|
|receptor signaling pathway via STAT|
|positive regulation of nitric oxide metabolic process|
|neuroinflammatory response|
|positive regulation of protein dephosphorylation|
|non-membrane spanning protein tyrosine kinase activity|
|interleukin-12-mediated signaling pathway|
|cellular response to interleukin-12|
|response to interleukin-12|
|response to axon injury|
|positive regulation of reactive oxygen species biosynthetic process|
|regulation of vascular smooth muscle cell proliferation|
|actin polymerization or depolymerization|
|macrophage activation|
|positive regulation of interleukin-1 beta production|
|activation of MAPKK activity|
|negative regulation of DNA binding|
|regulation of nitric oxide biosynthetic process|
|positive regulation of DNA binding|
|positive regulation of interleukin-1 production|
|mammary gland epithelium development|
|positive regulation of dephosphorylation|
|positive regulation of Ras protein signal transduction|
|positive regulation of cytokine biosynthetic process|
|positive regulation of tyrosine phosphorylation of STAT protein|
|regulation of muscle cell apoptotic process|
|intracellular steroid hormone receptor signaling pathway|
|positive regulation of small GTPase mediated signal transduction|
|interferon-gamma-mediated signaling pathway|
|positive regulation of insulin secretion|
|caveola|
|regulation of tyrosine phosphorylation of STAT protein|
|regulation of epithelial cell apoptotic process|
|erythrocyte differentiation|
|regulation of interleukin-1 beta production|
|postsynapse|
|positive regulation of receptor signaling pathway via JAK-STAT|
|positive regulation of smooth muscle cell proliferation|
|regulation of reactive oxygen species biosynthetic process|
|positive regulation of phosphatidylinositol 3-kinase signaling|
|positive regulation of tumor necrosis factor production|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|protein polymerization|
|protein tyrosine kinase activity|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of receptor signaling pathway via STAT|
|erythrocyte homeostasis|
|regulation of interleukin-1 production|
|positive regulation of reactive oxygen species metabolic process|
|positive regulation of peptide hormone secretion|
|extrinsic apoptotic signaling pathway|
|positive regulation of cold-induced thermogenesis|
|regulation of cytokine biosynthetic process|
|myeloid cell homeostasis|
|nuclear matrix|
|regulation of phosphoprotein phosphatase activity|
|tumor necrosis factor-mediated signaling pathway|
|steroid hormone mediated signaling pathway|
|regulation of phosphatidylinositol 3-kinase signaling|
|positive regulation of cell-substrate adhesion|
|mesoderm development|
|regulation of DNA binding|
|mammary gland development|
|positive regulation of hormone secretion|
|regulation of receptor signaling pathway via JAK-STAT|
|histone binding|
|regulation of smooth muscle cell proliferation|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of receptor signaling pathway via STAT|
|positive regulation of inflammatory response|
|regulation of protein dephosphorylation|
|heme binding|
|peptidyl-tyrosine phosphorylation|
|regulation of cold-induced thermogenesis|
|negative regulation of neuron apoptotic process|
|peptidyl-tyrosine modification|
|intrinsic apoptotic signaling pathway|
|regulation of tumor necrosis factor production|
|positive regulation of cysteine-type endopeptidase activity|
|regulation of tumor necrosis factor superfamily cytokine production|
|regeneration|
|cellular response to interferon-gamma|
|regulation of cytokine-mediated signaling pathway|
|intracellular receptor signaling pathway|
|hormone-mediated signaling pathway|
|negative regulation of binding|
|positive regulation of endopeptidase activity|
|positive regulation of apoptotic signaling pathway|
|negative regulation of cell-cell adhesion|
|regulation of response to cytokine stimulus|
|regulation of phosphatase activity|
|positive regulation of binding|
|regulation of insulin secretion|
|regulation of reactive oxygen species metabolic process|
|response to interferon-gamma|
|cellular response to steroid hormone stimulus|
|protein C-terminus binding|
|positive regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of peptidase activity|
|protein autophosphorylation|
|homeostasis of number of cells|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|regulation of peptide hormone secretion|
|regulation of dephosphorylation|
|regulation of cell-substrate adhesion|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|myeloid cell differentiation|
|membrane raft|
|protein kinase activity|
|actin filament organization|
|cellular response to oxidative stress|
|cellular response to tumor necrosis factor|
|regulation of cysteine-type endopeptidase activity|
|regulation of Ras protein signal transduction|
|regulation of heart contraction|
|regulation of peptidyl-tyrosine phosphorylation|
|positive regulation of DNA-binding transcription factor activity|
|positive regulation of MAP kinase activity|
|response to tumor necrosis factor|
|cellular response to peptide hormone stimulus|
|regulation of hormone secretion|
|positive regulation of protein secretion|
|negative regulation of cell adhesion|
|positive regulation of cytosolic calcium ion concentration|
|apoptotic signaling pathway|
|regulation of blood circulation|
|positive regulation of peptide secretion|
|blood coagulation|
|coagulation|
|hemostasis|
|response to antibiotic|
|regulation of neuron death|
|response to lipopolysaccharide|
|cellular response to peptide|
|response to molecule of bacterial origin|
|response to steroid hormone|
|regulation of cytosolic calcium ion concentration|
|activation of protein kinase activity|
|signaling receptor binding|
|regulation of inflammatory response|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|regulation of small GTPase mediated signal transduction|
|glutamatergic synapse|
|regulation of neurotransmitter levels|
|positive regulation of proteolysis|
|histone modification|
|cytoskeleton|
|MAPK cascade|
|covalent chromatin modification|
|regulation of binding|
|response to oxidative stress|
|response to peptide hormone|
|signal transduction by protein phosphorylation|
|regulation of cell-cell adhesion|
|regulation of apoptotic signaling pathway|
|positive regulation of cell adhesion|
|positive regulation of secretion by cell|
|axon development|
|gland development|
|focal adhesion|
|regulation of endopeptidase activity|
|positive regulation of cell activation|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|cellular calcium ion homeostasis|
|modulation of chemical synaptic transmission|
|regulation of trans-synaptic signaling|
|regulation of peptidase activity|
|positive regulation of cytokine production|
|calcium ion homeostasis|
|regulation of innate immune response|
|supramolecular fiber organization|
|positive regulation of establishment of protein localization|
|synaptic signaling|
|protein kinase binding|
|regulation of protein secretion|
|cellular divalent inorganic cation homeostasis|
|response to peptide|
|positive regulation of defense response|
|wound healing|
|divalent inorganic cation homeostasis|
|actin cytoskeleton organization|
|regulation of peptide secretion|
|regulation of body fluid levels|
|inflammatory response|
|positive regulation of cell migration|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of protein serine/threonine kinase activity|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|positive regulation of cell motility|
|positive regulation of protein kinase activity|
|regulation of hormone levels|
|positive regulation of cellular component movement|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|positive regulation of locomotion|
|cellular metal ion homeostasis|
|hemopoiesis|
|actin filament-based process|
|response to wounding|
|positive regulation of kinase activity|
|myeloid leukocyte activation|
|regulation of system process|
|cellular response to organonitrogen compound|
|positive regulation of response to external stimulus|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|metal ion homeostasis|
|cellular cation homeostasis|
|regulation of cell activation|
|positive regulation of apoptotic process|
|cellular ion homeostasis|
|immune system development|
|positive regulation of programmed cell death|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|neuron projection development|
|cytokine-mediated signaling pathway|
|negative regulation of cell population proliferation|
|regulation of cell adhesion|
|response to bacterium|
|regulation of cytokine production|
|positive regulation of cell death|
|chromatin organization|
|cation homeostasis|
|regulation of protein transport|
|enzyme linked receptor protein signaling pathway|
|inorganic ion homeostasis|
|regulation of proteolysis|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|innate immune response|
|positive regulation of hydrolase activity|
|regulation of multi-organism process|
|ion homeostasis|
|regulation of protein kinase activity|
|regulation of secretion|
|neuron development|
|cellular protein-containing complex assembly|
|regulation of cell migration|
|response to lipid|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|cellular homeostasis|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|response to organic cyclic compound|
|apoptotic process|
|leukocyte activation|
|defense response to other organism|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|positive regulation of transport|
|regulation of cellular component movement|
|negative regulation of cell death|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|neuron differentiation|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|chromosome organization|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|cell death|
|regulation of response to external stimulus|
|response to cytokine|
|cytoskeleton organization|
|chemical homeostasis|
|epithelium development|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|regulation of immune response|
|cell projection organization|
|negative regulation of multicellular organismal process|
|cellular response to endogenous stimulus|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|response to other organism|
|response to external biotic stimulus|
|G protein-coupled receptor signaling pathway|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|homeostatic process|
|cell development|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp271|CCT251545 0.2μM R06 exp271]]|-1.97|
|[[:results:exp531|THZ1 0.06μM R08 exp531]]|-1.93|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|-1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18623
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 3.42 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='JAK2 Expression in NALM6 Cells: 3.42'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>