Browse JAK2

Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Endomembrane system Peripheral membrane protein Cytoplasm Nucleus
Domain PF07714 Protein tyrosine kinase
PF00017 SH2 domain
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).

> Gene Ontology
 
Biological Process GO:0000060 protein import into nucleus, translocation
GO:0000186 activation of MAPKK activity
GO:0001819 positive regulation of cytokine production
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0002237 response to molecule of bacterial origin
GO:0002250 adaptive immune response
GO:0002262 myeloid cell homeostasis
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002793 positive regulation of peptide secretion
GO:0003013 circulatory system process
GO:0003015 heart process
GO:0006470 protein dephosphorylation
GO:0006606 protein import into nucleus
GO:0006809 nitric oxide biosynthetic process
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0006913 nucleocytoplasmic transport
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006979 response to oxidative stress
GO:0007015 actin filament organization
GO:0007162 negative regulation of cell adhesion
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0007262 STAT protein import into nucleus
GO:0007498 mesoderm development
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008015 blood circulation
GO:0008016 regulation of heart contraction
GO:0008154 actin polymerization or depolymerization
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009306 protein secretion
GO:0009755 hormone-mediated signaling pathway
GO:0009914 hormone transport
GO:0010656 negative regulation of muscle cell apoptotic process
GO:0010657 muscle cell apoptotic process
GO:0010658 striated muscle cell apoptotic process
GO:0010659 cardiac muscle cell apoptotic process
GO:0010660 regulation of muscle cell apoptotic process
GO:0010662 regulation of striated muscle cell apoptotic process
GO:0010664 negative regulation of striated muscle cell apoptotic process
GO:0010665 regulation of cardiac muscle cell apoptotic process
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
GO:0010810 regulation of cell-substrate adhesion
GO:0010811 positive regulation of cell-substrate adhesion
GO:0010817 regulation of hormone levels
GO:0010921 regulation of phosphatase activity
GO:0010922 positive regulation of phosphatase activity
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0015833 peptide transport
GO:0016311 dephosphorylation
GO:0016570 histone modification
GO:0016572 histone phosphorylation
GO:0017038 protein import
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0022407 regulation of cell-cell adhesion
GO:0022408 negative regulation of cell-cell adhesion
GO:0023061 signal release
GO:0030041 actin filament polymerization
GO:0030072 peptide hormone secretion
GO:0030073 insulin secretion
GO:0030099 myeloid cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030335 positive regulation of cell migration
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0030879 mammary gland development
GO:0031099 regeneration
GO:0031102 neuron projection regeneration
GO:0031103 axon regeneration
GO:0031349 positive regulation of defense response
GO:0031589 cell-substrate adhesion
GO:0031958 corticosteroid receptor signaling pathway
GO:0031959 mineralocorticoid receptor signaling pathway
GO:0032024 positive regulation of insulin secretion
GO:0032103 positive regulation of response to external stimulus
GO:0032147 activation of protein kinase activity
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032496 response to lipopolysaccharide
GO:0032516 positive regulation of phosphoprotein phosphatase activity
GO:0032611 interleukin-1 beta production
GO:0032612 interleukin-1 production
GO:0032640 tumor necrosis factor production
GO:0032651 regulation of interleukin-1 beta production
GO:0032652 regulation of interleukin-1 production
GO:0032680 regulation of tumor necrosis factor production
GO:0032731 positive regulation of interleukin-1 beta production
GO:0032732 positive regulation of interleukin-1 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0033002 muscle cell proliferation
GO:0033157 regulation of intracellular protein transport
GO:0033158 regulation of protein import into nucleus, translocation
GO:0033160 positive regulation of protein import into nucleus, translocation
GO:0033194 response to hydroperoxide
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033674 positive regulation of kinase activity
GO:0034101 erythrocyte homeostasis
GO:0034341 response to interferon-gamma
GO:0034504 protein localization to nucleus
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0035303 regulation of dephosphorylation
GO:0035304 regulation of protein dephosphorylation
GO:0035306 positive regulation of dephosphorylation
GO:0035307 positive regulation of protein dephosphorylation
GO:0035406 histone-tyrosine phosphorylation
GO:0035409 histone H3-Y41 phosphorylation
GO:0035722 interleukin-12-mediated signaling pathway
GO:0036473 cell death in response to oxidative stress
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0040017 positive regulation of locomotion
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042506 tyrosine phosphorylation of Stat5 protein
GO:0042508 tyrosine phosphorylation of Stat1 protein
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042522 regulation of tyrosine phosphorylation of Stat5 protein
GO:0042523 positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0042886 amide transport
GO:0042976 activation of Janus kinase activity
GO:0042977 activation of JAK2 kinase activity
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043388 positive regulation of DNA binding
GO:0043392 negative regulation of DNA binding
GO:0043401 steroid hormone mediated signaling pathway
GO:0043405 regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043434 response to peptide hormone
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0044057 regulation of system process
GO:0044744 protein targeting to nucleus
GO:0045088 regulation of innate immune response
GO:0045428 regulation of nitric oxide biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045785 positive regulation of cell adhesion
GO:0045822 negative regulation of heart contraction
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0046209 nitric oxide metabolic process
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046677 response to antibiotic
GO:0046777 protein autophosphorylation
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0046879 hormone secretion
GO:0046883 regulation of hormone secretion
GO:0046887 positive regulation of hormone secretion
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048545 response to steroid hormone
GO:0048659 smooth muscle cell proliferation
GO:0048660 regulation of smooth muscle cell proliferation
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0048678 response to axon injury
GO:0048732 gland development
GO:0048872 homeostasis of number of cells
GO:0050708 regulation of protein secretion
GO:0050714 positive regulation of protein secretion
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050796 regulation of insulin secretion
GO:0050817 coagulation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050878 regulation of body fluid levels
GO:0051047 positive regulation of secretion
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051100 negative regulation of binding
GO:0051101 regulation of DNA binding
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051258 protein polymerization
GO:0051272 positive regulation of cellular component movement
GO:0051402 neuron apoptotic process
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051767 nitric-oxide synthase biosynthetic process
GO:0051769 regulation of nitric-oxide synthase biosynthetic process
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0055074 calcium ion homeostasis
GO:0060047 heart contraction
GO:0060330 regulation of response to interferon-gamma
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060334 regulation of interferon-gamma-mediated signaling pathway
GO:0060396 growth hormone receptor signaling pathway
GO:0060397 JAK-STAT cascade involved in growth hormone signaling pathway
GO:0060398 regulation of growth hormone receptor signaling pathway
GO:0060399 positive regulation of growth hormone receptor signaling pathway
GO:0060416 response to growth hormone
GO:0060759 regulation of response to cytokine stimulus
GO:0061180 mammary gland epithelium development
GO:0061564 axon development
GO:0070671 response to interleukin-12
GO:0070997 neuron death
GO:0071346 cellular response to interferon-gamma
GO:0071349 cellular response to interleukin-12
GO:0071356 cellular response to tumor necrosis factor
GO:0071375 cellular response to peptide hormone stimulus
GO:0071378 cellular response to growth hormone stimulus
GO:0071383 cellular response to steroid hormone stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071706 tumor necrosis factor superfamily cytokine production
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072593 reactive oxygen species metabolic process
GO:0090087 regulation of peptide transport
GO:0090276 regulation of peptide hormone secretion
GO:0090277 positive regulation of peptide hormone secretion
GO:0090316 positive regulation of intracellular protein transport
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:0097696 STAT cascade
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1902593 single-organism nuclear import
GO:1902728 positive regulation of growth factor dependent skeletal muscle satellite cell proliferation
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903522 regulation of blood circulation
GO:1903523 negative regulation of blood circulation
GO:1903532 positive regulation of secretion by cell
GO:1903533 regulation of protein targeting
GO:1903555 regulation of tumor necrosis factor superfamily cytokine production
GO:1903557 positive regulation of tumor necrosis factor superfamily cytokine production
GO:1903829 positive regulation of cellular protein localization
GO:1904019 epithelial cell apoptotic process
GO:1904035 regulation of epithelial cell apoptotic process
GO:1904037 positive regulation of epithelial cell apoptotic process
GO:1904407 positive regulation of nitric oxide metabolic process
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904705 regulation of vascular smooth muscle cell proliferation
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
GO:1904951 positive regulation of establishment of protein localization
GO:1990874 vascular smooth muscle cell proliferation
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2000147 positive regulation of cell motility
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001057 reactive nitrogen species metabolic process
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001267 regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005126 cytokine receptor binding
GO:0005131 growth hormone receptor binding
GO:0005143 interleukin-12 receptor binding
GO:0008022 protein C-terminus binding
GO:0020037 heme binding
GO:0031701 angiotensin receptor binding
GO:0031702 type 1 angiotensin receptor binding
GO:0033130 acetylcholine receptor binding
GO:0035173 histone kinase activity
GO:0035400 histone tyrosine kinase activity
GO:0035401 histone kinase activity (H3-Y41 specific)
GO:0042169 SH2 domain binding
GO:0042393 histone binding
GO:0043548 phosphatidylinositol 3-kinase binding
GO:0043560 insulin receptor substrate binding
GO:0046906 tetrapyrrole binding
GO:0051427 hormone receptor binding
GO:0051428 peptide hormone receptor binding
GO:0070851 growth factor receptor binding
Cellular Component GO:0005775 vacuolar lumen
GO:0005901 caveola
GO:0009898 cytoplasmic side of plasma membrane
GO:0016363 nuclear matrix
GO:0019897 extrinsic component of plasma membrane
GO:0019898 extrinsic component of membrane
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0031904 endosome lumen
GO:0034399 nuclear periphery
GO:0044440 endosomal part
GO:0044853 plasma membrane raft
GO:0045121 membrane raft
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG hsa04062 Chemokine signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa04630 Jak-STAT signaling pathway
hsa04725 Cholinergic synapse
hsa04917 Prolactin signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-170984: ARMS-mediated activation
R-HSA-422475: Axon guidance
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-983231: Factors involved in megakaryocyte development and platelet production
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-392451: G beta
R-HSA-397795: G-protein beta
R-HSA-388396: GPCR downstream signaling
R-HSA-114604: GPVI-mediated activation cascade
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-982772: Growth hormone receptor signaling
R-HSA-109582: Hemostasis
R-HSA-2428924: IGF1R signaling cascade
R-HSA-6788467: IL-6-type cytokine receptor ligand interactions
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-913531: Interferon Signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-6783589: Interleukin-6 family signaling
R-HSA-1059683: Interleukin-6 signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-112411: MAPK1 (ERK2) activation
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-110056: MAPK3 (ERK1) activation
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-6802957: Oncogenic MAPK signaling
R-HSA-6802955: Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-1170546: Prolactin receptor signaling
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673000: RAF activation
R-HSA-112409: RAF-independent MAPK1/3 activation
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-3214858: RMTs methylate histone arginines
R-HSA-877312: Regulation of IFNG signaling
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-162582: Signal Transduction
R-HSA-6802952: Signaling by BRAF and RAF fusions
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-6802949: Signaling by RAS mutants
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-6802946: Signaling by moderate kinase activity BRAF mutants
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between JAK2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between JAK2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26762740Non-Small Cell Lung CarcinomaInhibit immunity (T cell function)PD-L1 Is Upregulated by Simultaneous Amplification of?the PD-L1 and JAK2 Genes in Non-Small Cell Lung?Cancer.
26676749Head and Neck Squamous Cell CarcinomaInhibit immunity (T cell function)Interferon gamma (IFNγ) and the epidermal growth factor receptor (EGFR) utilize Janus kinase 2 (JAK2) as a common signaling node to transmit tumor cell-mediated extrinsic or intrinsic signals, respectively. Collectively, our findings suggest a novel role for JAK2/STAT1 in EGFR-mediated immune evasion, and therapies targeting this signaling axis may be beneficial to block PD-L1 upregulation found in a large subset of HNC tumors.
28783722MelanomaPromote immunity (T cell function); essential for immunotherapyFor example, loss-of-function mutations in β -2-microglobulin (B2M) and Janus kinases (JAK1 and JAK2) have been reported in patients unresponsive to immunotherapies.; Loss of expression of these 19 genes within tumours could diminish or extinguish the presentation of tumour antigens (including HLA-A, HLA-F, B2M, TAP1 and TAP2); T cell co- stimulation (ICAM1, CLECL1, LILRA1 and LILRA3); or cytokine production and signalling (JAK2 and STAT1) in the tumour microenvironment that drive infiltration and activation of T cells, and thus serve as a principal mechanism in immune evasion.
27433843MelanomaPromote immunityWhole-exome sequencing detected clonal selection and outgrowth of the acquired resistant tumors and, in two of the four patients, revealed resistance-associated loss-of-function mutations in the genes encoding interferon-receptor-associated Janus kinase 1 (JAK1) or Janus kinase 2 (JAK2), concurrent with deletion of the wild-type allele. JAK1 and JAK2 truncating mutations resulted in a lack of response to interferon gamma, including insensitivity to its antiproliferative effects on cancer cells.
24963042Essential ThrombocythemiaPromote immunitySurvival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status.
29662190Ovarian CarcinomaInhibit immunity immunotherapy targetThese findings not only identify a novel ROS-IL-11-JAK2-mediated platinum resistance mechanism but also provide a new strategy for using LY2784544- or IL-11-mediated immunotherapy to treat platinum-resistant ovarian cancer.
29215754Head and Neck Squamous Cell CarcinomaInhibit immunityInhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived suppressor cells in head and neck cancer. Moreover, in HNSCC transgenic mouse model, inhibiting JAK2/STAT3 not only suppressed angiogenesis but also reduced MDSCs in the tumor microenvironment through suppressing VEGFA and CK2. Our findings demonstrated the close relationship between angiogenesis and MDSCs in HNSCC, and inhibition of JAK2/STAT3 could reduce tumor-induced angiogenesis and decrease MDSCs.
29467301Myeloproliferative NeoplasmInhibit immunityWe show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2V617F-myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition.
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of JAK2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: 3.10; FDR: 0.000150 Sensitive to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: 3.10; FDR: 0.000381 Sensitive to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.62 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of JAK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.250.495
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.6690.544
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0530.949
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1170.732
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1750.921
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.040.986
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1250.75
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2820.842
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.050.975
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.8170.366
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2860.319
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1020.336
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of JAK2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.15.91.21
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1031033.3-23.30.423
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.3014.30.238
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of JAK2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of JAK2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by JAK2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of JAK2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of JAK2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between JAK2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolJAK2
NameJanus kinase 2
Aliases JTK10; THCYT3; JAK-2; Janus kinase 2 (a protein tyrosine kinase); Tyrosine-protein kinase JAK2
Chromosomal Location9p24
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting JAK2 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting JAK2.
ID Name Drug Type Targets #Targets
DB047162-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONESmall MoleculeDAPK3, JAK1, JAK2, JAK3, TYK25
DB05243XL019Small MoleculeJAK21
DB071615-phenyl-1H-indazol-3-amineSmall MoleculeJAK21
DB071624-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamideSmall MoleculeJAK21
DB080674-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUMSmall MoleculeJAK21
DB08877RuxolitinibSmall MoleculeJAK1, JAK22
DB08895TofacitinibSmall MoleculeJAK1, JAK2, JAK3, TYK24
DB11817BaricitinibSmall MoleculeJAK1, JAK2, JAK3, PTK2B4