Homo sapiens Gene: JAK2
Summary
InnateDB Gene IDBG-47039.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol JAK2
Gene Name Janus kinase 2
Synonyms JTK10; THCYT3;
Species Homo sapiens
Ensembl Gene ENSG00000096968
Encoded Proteins
Janus kinase 2
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
JAK2 binds to the majority of the known members of the cytokine family of receptors and ligand-receptor binding leads to activation of the associated JAK2 molecules, resulting in rapid autophosphorylation of multiple tyrosines within JAK2. Tyrosine 813 is a site of autophosphorylation in JAK2 and is the SH2-B beta-binding site within JAK2 that is required for SH2-B beta to enhance activation of JAK2.
JAK2 and JAK1 tyrosine kinases physically associate with the gamma chain and beta chain of the interleukin 2 (IL-2) receptor , respectively, suggesting that regulation of the kinases may be linked to IL-2-induced signal transduction.
JAK2 inhibition prevents innate immune responses and rescues animals from sepsis by specifically preventing LPS-induced STAT3 tyrosine phosphorylation without affecting serine phosphorylation in macrophages and by preventing the activation of the canonical p65RelA/p50NF-kappaB1 pathway but not the other NF-kappaB proteins.
JAK2 functions downstream of TLR2-stimulation to induce the expression of the monocyte chemoattractant protein 1, CCL2. (Demonstrated in mice)
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Jak2 inhibition prevents innate immune responses and rescues animals from sepsis by specifically preventing LPS-induced STAT3 tyrosine phosphorylation without affecting serine phosphorylation in macrophages and by preventing the activation of the canonical p65RelA/p50NF-kappaB1 pathway but not the other NF-kappaB proteins.
[Mus musculus] Jak2 functions downstream of Tlr2-stimulation to induce the expression of the monocyte chemoattractant protein 1, Ccl2.
Entrez Gene
Summary 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]
Gene Information
Type Protein coding
Genomic Location Chromosome 9:4985033-5128183
Strand Forward strand
Band p24.1
Transcripts
ENST00000381652 ENSP00000371067
ENST00000476574
ENST00000487310
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 141 experimentally validated interaction(s) in this database.
They are also associated with 44 interaction(s) predicted by orthology.
Experimentally validated
Total 141 [view]
Protein-Protein 140 [view]
Protein-DNA 1 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 44 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005102 receptor binding
GO:0005131 growth hormone receptor binding
GO:0005143 interleukin-12 receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008022 protein C-terminus binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0019901 protein kinase binding
GO:0020037 heme binding
GO:0031702 type 1 angiotensin receptor binding
GO:0033130 acetylcholine receptor binding
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:0051428 peptide hormone receptor binding
Biological Process
GO:0000186 activation of MAPKK activity
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006928 cellular component movement
GO:0006979 response to oxidative stress
GO:0007165 signal transduction
GO:0007167 enzyme linked receptor protein signaling pathway
GO:0007186 G-protein coupled receptor signaling pathway
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:0008284 positive regulation of cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009755 hormone-mediated signaling pathway
GO:0010811 positive regulation of cell-substrate adhesion
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0022408 negative regulation of cell-cell adhesion
GO:0030041 actin filament polymerization
GO:0030099 myeloid cell differentiation
GO:0030154 cell differentiation
GO:0030218 erythrocyte differentiation
GO:0030335 positive regulation of cell migration
GO:0031103 axon regeneration
GO:0031959 mineralocorticoid receptor signaling pathway
GO:0032024 positive regulation of insulin secretion
GO:0032496 response to lipopolysaccharide
GO:0032516 positive regulation of phosphoprotein phosphatase activity
GO:0032731 positive regulation of interleukin-1 beta production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0033160 positive regulation of protein import into nucleus, translocation
GO:0033194 response to hydroperoxide
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0034050 host programmed cell death induced by symbiont
GO:0034612 response to tumor necrosis factor
GO:0035409 histone H3-Y41 phosphorylation
GO:0035556 intracellular signal transduction
GO:0035722 interleukin-12-mediated signaling pathway
GO:0042503 tyrosine phosphorylation of Stat3 protein
GO:0042506 tyrosine phosphorylation of Stat5 protein
GO:0042508 tyrosine phosphorylation of Stat1 protein
GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0042523 positive regulation of tyrosine phosphorylation of Stat5 protein
GO:0042977 activation of JAK2 kinase activity
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043388 positive regulation of DNA binding
GO:0043392 negative regulation of DNA binding
GO:0043524 negative regulation of neuron apoptotic process
GO:0045087 innate immune response (InnateDB)
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045597 positive regulation of cell differentiation
GO:0045822 negative regulation of heart contraction
GO:0046677 response to antibiotic
GO:0046777 protein autophosphorylation
GO:0048008 platelet-derived growth factor receptor signaling pathway
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050867 positive regulation of cell activation
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
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:0060399 positive regulation of growth hormone receptor signaling pathway
GO:0061180 mammary gland epithelium development
GO:0070671 response to interleukin-12
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005901 caveola
GO:0016020 membrane
GO:0016363 nuclear matrix
GO:0031904 endosome lumen
GO:0045121 membrane raft
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
Notch pathway
EGFR1 pathway
KitReceptor pathway
IL2 pathway
IL3 pathway
IL4 pathway
IL5 pathway
IL6 pathway
Leptin pathway
TSH pathway
TSLP pathway
Prolactin pathway
IL11 pathway
Oncostatin_M pathway
REACTOME
Signaling by FGFR in disease pathway
SHC-related events pathway
MyD88 dependent cascade initiated on endosome pathway
Developmental Biology pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Signaling by EGFR in Cancer pathway
Downstream signaling of activated FGFR pathway
Signalling to p38 via RIT and RIN pathway
FRS2-mediated cascade pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Gastrin-CREB signalling pathway via PKC and MAPK pathway
SOS-mediated signalling pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
ERK2 activation pathway
SHC1 events in ERBB4 signaling pathway
DAP12 signaling pathway
NCAM signaling for neurite out-growth pathway
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) pathway
GRB2 events in ERBB2 signaling pathway
Interleukin-3, 5 and GM-CSF signaling pathway
MyD88 cascade initiated on plasma membrane pathway
Signaling by VEGF pathway
Signaling by EGFR pathway
Cytokine Signaling in Immune system pathway
Signaling by GPCR pathway
Innate Immune System pathway
Signaling by ERBB4 pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
SHC-related events triggered by IGF1R pathway
Platelet activation, signaling and aggregation pathway
Signaling by SCF-KIT pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
G-protein beta:gamma signalling pathway
Frs2-mediated activation pathway
Toll-Like Receptors Cascades pathway
Axon guidance pathway
RAF/MAP kinase cascade pathway
Fc epsilon receptor (FCERI) signaling pathway
Interleukin-6 signaling pathway
Signal Transduction pathway
GPCR downstream signaling pathway
Interferon Signaling pathway
MAP kinase activation in TLR cascade pathway
IRS-mediated signalling pathway
ERK1 activation pathway
SHC1 events in EGFR signaling pathway
Prolactin receptor signaling pathway
SHC-mediated signalling pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Downstream signal transduction pathway
GRB2 events in EGFR signaling pathway
VEGFR2 mediated cell proliferation pathway
Insulin receptor signalling cascade pathway
GPVI-mediated activation cascade pathway
Interleukin-2 signaling pathway
Growth hormone receptor signaling pathway
Interleukin receptor SHC signaling pathway
Signaling by Interleukins pathway
VEGFA-VEGFR2 Pathway pathway
Signalling to ERKs pathway
NGF signalling via TRKA from the plasma membrane pathway
IRS-related events triggered by IGF1R pathway
Chromatin organization pathway
IRS-related events pathway
RMTs methylate histone arginines pathway
Interferon gamma signaling pathway
SHC1 events in ERBB2 signaling pathway
Factors involved in megakaryocyte development and platelet production pathway
IGF1R signaling cascade pathway
Chromatin modifying enzymes pathway
ARMS-mediated activation pathway
Prolonged ERK activation events pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
Signaling by FGFR pathway
Regulation of IFNG signaling pathway
Signalling to RAS pathway
Signaling by PDGF pathway
Signaling by Insulin receptor pathway
Signaling by ERBB2 pathway
TRIF-mediated TLR3/TLR4 signaling pathway
G beta:gamma signalling through PI3Kgamma pathway
ERK activation pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Nuclear signaling by ERBB4 pathway
Disease pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
Signaling by Leptin pathway
FCERI mediated MAPK activation pathway
Hemostasis pathway
DAP12 interactions pathway
KEGG
Chemokine signaling pathway pathway
Jak-STAT signaling pathway pathway
Adipocytokine signaling pathway pathway
Leishmaniasis pathway
Toxoplasmosis pathway
INOH
IFN gamma signaling pathway
IL-23 signaling pathway
IL-7 signaling pathway
IL-3 signaling pathway
JAK STAT pathway and regulation pathway
IL-12 signaling pathway
Growth hormone signaling pathway
EPO signaling pathway pathway
IL-6 signaling pathway
IL-5 signaling pathway
LIF signaling pathway
TPO signaling pathway
VEGF signaling pathway pathway
PID BIOCARTA
No2-dependent il-12 pathway in nk cells [Biocarta view]
Inhibition of cellular proliferation by gleevec [Biocarta view]
Chaperones modulate interferon signaling pathway [Biocarta view]
Il 3 signaling pathway [Biocarta view]
Il 6 signaling pathway [Biocarta view]
Role of erbb2 in signal transduction and oncology [Biocarta view]
Epo signaling pathway [Biocarta view]
Il12 and stat4 dependent signaling pathway in th1 development [Biocarta view]
Stat3 signaling pathway [Biocarta view]
Growth hormone signaling pathway [Biocarta view]
Tpo signaling pathway [Biocarta view]
Bioactive peptide induced signaling pathway [Biocarta view]
Erythropoietin mediated neuroprotection through nf-kb [Biocarta view]
Ifn gamma signaling pathway [Biocarta view]
PID NCI
CXCR4-mediated signaling events
ErbB4 signaling events
IL27-mediated signaling events
IL12-mediated signaling events
Signaling events mediated by PTP1B
Notch-mediated HES/HEY network
EPO signaling pathway
Endothelins
Signaling events mediated by Stem cell factor receptor (c-Kit)
IL23-mediated signaling events
IL4-mediated signaling events
ErbB2/ErbB3 signaling events
S1P3 pathway
IL3-mediated signaling events
SHP2 signaling
GMCSF-mediated signaling events
PDGFR-beta signaling pathway
IL6-mediated signaling events
IFN-gamma pathway
IL5-mediated signaling events
Cross-References
SwissProt O60674
TrEMBL F5H5U8 Q8IXP2
UniProt Splice Variant
Entrez Gene 3717
UniGene Hs.656213
RefSeq NM_004972 XM_005251455
HUGO HGNC:6192
OMIM 147796
CCDS CCDS6457
HPRD
IMGT
EMBL AF001362 AF005216 AF058925 AL158147 AL161450 AL513350 BC039695
GenPept AAB82092 AAC23653 AAC23982 AAH39695 CAD13329
RNA Seq Atlas 3717