DegronMD - O60674(JAK2)

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. 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}. View more >>

GO - Biological processes (BP): actin filament polymerization [GO:0030041]; activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919]; activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097296]; activation of Janus kinase activity [GO:0042976]; adaptive immune response [GO:0002250]; apoptotic process [GO:0006915]; axon regeneration [GO:0031103]; cell differentiation [GO:0030154]; cellular response to dexamethasone stimulus [GO:0071549]; cellular response to interleukin-3 [GO:0036016]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to virus [GO:0098586]; chromatin organization [GO:0006325]; collagen-activated signaling pathway [GO:0038065]; cytokine-mediated signaling pathway [GO:0019221]; enzyme linked receptor protein signaling pathway [GO:0007167]; erythrocyte differentiation [GO:0030218]; extrinsic apoptotic signaling pathway [GO:0097191]; G protein-coupled receptor signaling pathway [GO:0007186]; granulocyte-macrophage colony-stimulating factor signaling pathway [GO:0038157]; growth hormone receptor signaling pathway [GO:0060396]; growth hormone receptor signaling pathway via JAK-STAT [GO:0060397]; histone H3-Y41 phosphorylation [GO:0035409]; immune response [GO:0006955]; interferon-gamma-mediated signaling pathway [GO:0060333]; interleukin-12-mediated signaling pathway [GO:0035722]; interleukin-35-mediated signaling pathway [GO:0070757]; interleukin-6-mediated signaling pathway [GO:0070102]; intracellular signal transduction [GO:0035556]; intrinsic apoptotic signaling pathway in response to oxidative stress [GO:0008631]; mammary gland epithelium development [GO:0061180]; mesoderm development [GO:0007498]; microglial cell activation [GO:0001774]; mineralocorticoid receptor signaling pathway [GO:0031959]; modulation of chemical synaptic transmission [GO:0050804]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of cell-cell adhesion [GO:0022408]; negative regulation of cell population proliferation [GO:0008285]; negative regulation of DNA binding [GO:0043392]; negative regulation of heart contraction [GO:0045822]; negative regulation of neuron apoptotic process [GO:0043524]; peptidyl-tyrosine phosphorylation [GO:0018108]; platelet-derived growth factor receptor signaling pathway [GO:0048008]; positive regulation of apoptotic signaling pathway [GO:2001235]; positive regulation of cell differentiation [GO:0045597]; positive regulation of cell migration [GO:0030335]; positive regulation of cell-substrate adhesion [GO:0010811]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of DNA binding [GO:0043388]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; 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 inflammatory response [GO:0050729]; positive regulation of insulin secretion [GO:0032024]; positive regulation of interferon-gamma production [GO:0032729]; positive regulation of interleukin-17 production [GO:0032740]; positive regulation of interleukin-1 beta production [GO:0032731]; positive regulation of leukocyte proliferation [GO:0070665]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of MHC class II biosynthetic process [GO:0045348]; positive regulation of natural killer cell proliferation [GO:0032819]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of nitric-oxide synthase biosynthetic process [GO:0051770]; positive regulation of NK T cell proliferation [GO:0051142]; positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731]; positive regulation of phosphatidylinositol 3-kinase signaling [GO:0014068]; positive regulation of phosphoprotein phosphatase activity [GO:0032516]; 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 receptor signaling pathway via JAK-STAT [GO:0046427]; positive regulation of signaling receptor activity [GO:2000273]; positive regulation of SMAD protein signal transduction [GO:0060391]; positive regulation of T cell proliferation [GO:0042102]; positive regulation of T-helper 17 type immune response [GO:2000318]; positive regulation of transcription by RNA polymerase II [GO:0045944]; 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]; postsynapse to nucleus signaling pathway [GO:0099527]; programmed cell death induced by symbiont [GO:0034050]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; receptor signaling pathway via JAK-STAT [GO:0007259]; regulation of apoptotic process [GO:0042981]; regulation of inflammatory response [GO:0050727]; regulation of nitric oxide biosynthetic process [GO:0045428]; regulation of receptor signaling pathway via JAK-STAT [GO:0046425]; response to amine [GO:0014075]; response to antibiotic [GO:0046677]; response to hydroperoxide [GO:0033194]; response to interleukin-12 [GO:0070671]; response to lipopolysaccharide [GO:0032496]; response to tumor necrosis factor [GO:0034612]; signal transduction [GO:0007165]; tumor necrosis factor-mediated signaling pathway [GO:0033209]; tyrosine phosphorylation of STAT protein [GO:0007260] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.V911A	TCGA-AP-A051	UCEC	TCGA	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation rewiring degron network	0.0556
p.R922W	TCGA-EA-A410	CESC	TCGA	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.8634
p.R922W	DO49929	CESC	ICGC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.8634
p.D919G	DO23002	LIHC	ICGC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation rewiring degron network	0.2778
p.K926R	SIDM00845	Burkitt's Lymphoma	GDSC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.6126
p.Y934N	SIDM00112	Kidney Carcinoma	GDSC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation blocking phosphorylation signal	0.6389
p.Y934N	ACH-000428	Kidney Cancer	CCLE	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation blocking phosphorylation signal	0.6389
p.Y934N	U031	kidney	COSMIC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation blocking phosphorylation signal	0.6389
p.K912T	SIDM00118	Colorectal Carcinoma	GDSC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation substituting flanking lysine	0.1944
p.K912T	ACH-001081	Colon/Colorectal Cancer	CCLE	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation substituting flanking lysine	0.1944
p.K912T	HCC2998	large intestine	COSMIC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation substituting flanking lysine	0.1944
p.R923H	SIDM01617	Endometrial Carcinoma	GDSC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.7133
p.R923H	ACH-000994	Endometrial/Uterine Cancer	CCLE	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.7133
p.R923C	SIDM01409	Bladder Carcinoma	GDSC	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.719
p.R923C	ACH-000834	Bladder Cancer	CCLE	GRRNLKLIM	DEG_APCC_DBOX_1	921:929	Mutation altering degron motif	0.719

DegronMD: protein-targeted degradation, mutation and drug response to degrons

JAK2

UniProt ID: O60674

Entrez ID: 3717

Protein name: Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for JAK2 in