IRS1 and JAK2

Data Source:
HPRD (in vivo)

		IRS1	JAK2
Description		insulin receptor substrate 1	Janus kinase 2
Image
GO Annotations	Cellular Component	Nucleus Nucleoplasm Cytoplasm Cytosol Plasma Membrane Insulin Receptor Complex Caveola Intracellular Membrane-bounded Organelle	Euchromatin Nucleus Nucleoplasm Nucleolus Cytoplasm Cytosol Cytoskeleton Plasma Membrane Caveola Focal Adhesion Endosome Lumen Membrane Raft Postsynapse Glutamatergic Synapse
	Molecular Function	Phosphotyrosine Residue Binding Transmembrane Receptor Protein Tyrosine Kinase Adaptor Activity Protein Kinase C Binding Insulin Receptor Binding Insulin-like Growth Factor Receptor Binding Protein Binding Signaling Receptor Complex Adaptor Activity SH2 Domain Binding Phosphatidylinositol 3-kinase Binding	Protein Kinase Activity Protein Tyrosine Kinase Activity Non-membrane Spanning Protein Tyrosine Kinase Activity Signaling Receptor Binding Growth Hormone Receptor Binding Interleukin-12 Receptor Binding Protein Binding ATP Binding Protein C-terminus Binding Protein Kinase Binding Heme Binding Type 1 Angiotensin Receptor Binding Acetylcholine Receptor Binding Histone Kinase Activity (H3-Y41 Specific) SH2 Domain Binding Histone Binding Identical Protein Binding Phosphatidylinositol 3-kinase Binding Insulin Receptor Substrate Binding Metal Ion Binding Peptide Hormone Receptor Binding
	Biological Process	MAPK Cascade Signal Transduction Positive Regulation Of Cell Population Proliferation Insulin Receptor Signaling Pathway Positive Regulation Of Glucose Metabolic Process Phosphatidylinositol 3-kinase Signaling Positive Regulation Of Fatty Acid Beta-oxidation Response To Insulin Cellular Response To Insulin Stimulus Interleukin-7-mediated Signaling Pathway Glucose Homeostasis Response To Peptide Hormone Positive Regulation Of Phosphatidylinositol 3-kinase Activity Positive Regulation Of Glycogen Biosynthetic Process Positive Regulation Of Glucose Import Negative Regulation Of Insulin Receptor Signaling Pathway Positive Regulation Of Insulin Receptor Signaling Pathway Negative Regulation Of Insulin Secretion Insulin-like Growth Factor Receptor Signaling Pathway Phosphatidylinositol-mediated Signaling Positive Regulation Of Protein Kinase B Signaling Cellular Response To Fatty Acid	MAPK Cascade Activation Of MAPKK Activity Microglial Cell Activation Adaptive Immune Response Protein Phosphorylation Apoptotic Process Activation Of Cysteine-type Endopeptidase Activity Involved In Apoptotic Process Signal Transduction Enzyme Linked Receptor Protein Signaling Pathway G Protein-coupled Receptor Signaling Pathway Positive Regulation Of Cytosolic Calcium Ion Concentration Receptor Signaling Pathway Via JAK-STAT Tyrosine Phosphorylation Of STAT Protein Mesoderm Development Blood Coagulation Negative Regulation Of Cell Population Proliferation Intrinsic Apoptotic Signaling Pathway In Response To Oxidative Stress Negative Regulation Of Cardiac Muscle Cell Apoptotic Process Positive Regulation Of Cell-substrate Adhesion Positive Regulation Of Phosphatidylinositol 3-kinase Signaling Peptidyl-tyrosine Phosphorylation Cytokine-mediated Signaling Pathway Negative Regulation Of Cell-cell Adhesion Actin Filament Polymerization Cell Differentiation Erythrocyte Differentiation Positive Regulation Of Cell Migration Axon Regeneration Mineralocorticoid Receptor Signaling Pathway Positive Regulation Of Insulin Secretion Response To Lipopolysaccharide Positive Regulation Of Phosphoprotein Phosphatase Activity Positive Regulation Of Interleukin-1 Beta Production Positive Regulation Of Tumor Necrosis Factor Production Response To Hydroperoxide Tumor Necrosis Factor-mediated Signaling Pathway Response To Tumor Necrosis Factor Histone H3-Y41 Phosphorylation Intracellular Signal Transduction Interleukin-12-mediated Signaling Pathway Interleukin-23-mediated Signaling Pathway Positive Regulation Of Protein Import Into Nucleus Positive Regulation Of Tyrosine Phosphorylation Of STAT Protein Activation Of Janus Kinase Activity Regulation Of Apoptotic Process Positive Regulation Of DNA Binding Negative Regulation Of DNA Binding Negative Regulation Of Neuron Apoptotic Process Positive Regulation Of MHC Class II Biosynthetic Process Regulation Of Nitric Oxide Biosynthetic Process Positive Regulation Of Nitric Oxide Biosynthetic Process Positive Regulation Of Cell Differentiation Negative Regulation Of Heart Contraction Regulation Of Receptor Signaling Pathway Via JAK-STAT Positive Regulation Of Ras Protein Signal Transduction Response To Antibiotic Protein Autophosphorylation Platelet-derived Growth Factor Receptor Signaling Pathway Regulation Of Inflammatory Response Positive Regulation Of Inflammatory Response Positive Regulation Of Peptidyl-tyrosine Phosphorylation Modulation Of Chemical Synaptic Transmission Positive Regulation Of Cell Activation Positive Regulation Of DNA-binding Transcription Factor Activity Positive Regulation Of Nitric-oxide Synthase Biosynthetic Process Interferon-gamma-mediated Signaling Pathway Regulation Of Interferon-gamma-mediated Signaling Pathway Positive Regulation Of SMAD Protein Signal Transduction Growth Hormone Receptor Signaling Pathway Growth Hormone Receptor Signaling Pathway Via JAK-STAT Positive Regulation Of Growth Hormone Receptor Signaling Pathway Mammary Gland Epithelium Development Interleukin-6-mediated Signaling Pathway Interleukin-27-mediated Signaling Pathway Response To Interleukin-12 Interleukin-35-mediated Signaling Pathway Extrinsic Apoptotic Signaling Pathway Activation Of Cysteine-type Endopeptidase Activity Involved In Apoptotic Signaling Pathway Postsynapse To Nucleus Signaling Pathway Positive Regulation Of Cold-induced Thermogenesis Positive Regulation Of Growth Factor Dependent Skeletal Muscle Satellite Cell Proliferation Positive Regulation Of Epithelial Cell Apoptotic Process Positive Regulation Of Vascular Associated Smooth Muscle Cell Proliferation Positive Regulation Of Signaling Receptor Activity
Pathways		PI3K Cascade IRS-mediated signalling SOS-mediated signalling SOS-mediated signalling PIP3 activates AKT signaling Interleukin-7 signaling PI3K/AKT activation PI3K/AKT activation Constitutive Signaling by Aberrant PI3K in Cancer IRS-related events triggered by IGF1R Signaling by Leptin RAF/MAP kinase cascade PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling IRS activation Signal attenuation Activated NTRK3 signals through PI3K Growth hormone receptor signaling	Interleukin-6 signaling Interleukin-6 signaling MAPK3 (ERK1) activation MAPK1 (ERK2) activation Prolactin receptor signaling Prolactin receptor signaling Signaling by SCF-KIT Signaling by Leptin RMTs methylate histone arginines Interleukin-3, Interleukin-5 and GM-CSF signaling Interleukin-3, Interleukin-5 and GM-CSF signaling RAF activation RAF/MAP kinase cascade Interleukin-4 and Interleukin-13 signaling IL-6-type cytokine receptor ligand interactions Signaling by moderate kinase activity BRAF mutants Signaling by BRAF and RAF fusions Paradoxical activation of RAF signaling by kinase inactive BRAF Cyclin D associated events in G1 Interferon gamma signaling Regulation of IFNG signaling Regulation of IFNG signaling Interleukin-20 family signaling Interleukin-35 Signalling Signaling by Erythropoietin Interleukin-12 signaling Interleukin-12 signaling Interleukin-23 signaling Interleukin-23 signaling Interleukin-27 signaling Interleukin-27 signaling Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Erythropoietin activates Phospholipase C gamma (PLCG) Erythropoietin activates STAT5 Erythropoietin activates RAS Erythropoietin activates RAS Interleukin receptor SHC signaling Signaling downstream of RAS mutants Signaling by RAF1 mutants Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants Potential therapeutics for SARS Growth hormone receptor signaling Growth hormone receptor signaling Factors involved in megakaryocyte development and platelet production
Drugs		[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID	2-tert-butyl-9-fluoro-1,6-dihydrobenzo[h]imidazo[4,5-f]isoquinolin-7-one XL019 5-phenyl-1H-indazol-3-amine 4-(3-amino-1H-indazol-5-yl)-N-tert-butylbenzenesulfonamide 4-[(2-{4-[(CYCLOPROPYLCARBAMOYL)AMINO]-1H-PYRAZOL-3-YL}-1H-BENZIMIDAZOL-6-YL)METHYL]MORPHOLIN-4-IUM Ruxolitinib Tofacitinib Baricitinib Entrectinib Fostamatinib Fedratinib Zanubrutinib Pralsetinib
Diseases			Polycythemia vera
GWAS		Adiponectin levels ( 22479202 31178129) Adiposity ( 21706003) Apolipoprotein A1 levels ( 32203549) Appendicular lean mass ( 33097823 28724990) Birth weight ( 31043758) BMI (adjusted for smoking behaviour) ( 28443625) BMI in non-smokers ( 28443625) Body fat percentage ( 26833246 28270201) Body mass index (joint analysis main effects and smoking interaction) ( 28443625) Circulating leptin levels or type 2 diabetes ( 32341051) Fasting blood insulin ( 25631608 22581228) Fasting blood insulin (BMI interaction) ( 22581228) Glucose homeostasis traits ( 25524916) HDL cholesterol ( 24097068 25961943 20686565) HDL cholesterol levels ( 32203549 28334899) Heel bone mineral density ( 30598549) High light scatter reticulocyte count ( 32888494) High light scatter reticulocyte percentage of red cells ( 32888494) Immature fraction of reticulocytes ( 32888494) Insulin levels in response to oral glucose tolerance test (fasting) ( 29093273) Lean body mass ( 28724990) Metabolite levels ( 23823483) Modified Stumvoll Insulin Sensitivity Index (model adjusted for BMI) ( 27416945) Problematic alcohol use ( 32451486) Sexual dimorphism in anthropometric traits ( 23754948) Triglyceride levels ( 32203549 28334899) Triglycerides ( 24097068 25961943 20686565) Type 2 diabetes ( 22885922 24509480 29358691 30297969 19734900 31118516 20581827) Visceral adipose tissue/subcutaneous adipose tissue ratio ( 22589738) Waist circumference ( 25673412) Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction) ( 28448500) Waist circumference adjusted for BMI in active individuals ( 28448500) Waist circumference adjusted for body mass index ( 28448500) Waist-hip ratio ( 25673412) Waist-to-hip ratio adjusted for BMI x sex interaction ( 26426971)	Allergic disease (asthma, hay fever or eczema) ( 29083406) Chronic inflammatory diseases (ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy) ( 26974007) Crohn's disease ( 18587394 21102463 23266558) Eosinophil counts ( 32888494 27863252) Eosinophil percentage of white cells ( 32888494) HDL cholesterol ( 30275531) Height ( 31562340) Inflammatory bowel disease ( 23128233) LDL cholesterol ( 30275531) Mean corpuscular hemoglobin ( 32888494) Mean corpuscular volume ( 32888494) Mean reticulocyte volume ( 32888494) Mean spheric corpuscular volume ( 32888494) Monocyte percentage of white cells ( 32888494) Myeloproliferative neoplasms ( 19287384 25849990 33057200) Neutrophil count ( 32888494) Pediatric autoimmune diseases ( 26301688) Platelet count ( 32888494 27863252 24777453 28031487) Plateletcrit ( 32888494 27863252) Psoriatic arthritis ( 26626624) Red blood cell count ( 32888494) Sum eosinophil basophil counts ( 27863252) Systemic lupus erythematosus ( 27399966) Total cholesterol levels ( 30275531) Ulcerative colitis ( 19915573 26398853 20228799 21297633) White blood cell count ( 32888494)
Interacting Genes		79 interacting genes: AKT1 ALK AP3S1 APP ATP2A1 ATP2A2 ATP2A3 BCL2L1 BCR CAV1 CDH1 CHUK CRK CSNK2A1 CSNK2B EGFR ERBB2 FBXO25 FBXW8 FER FES FYN GHR GRB10 GRB14 GRB2 IGF1R IKBKB IL4R INSR JAK1 JAK2 JAK3 MAPK1 MAPK3 MAPK8 MAPK9 MTOR NCK2 NEDD4 NPM1 NTRK1 NUMB PASK PDPK1 PELI1 PHIP PIK3R1 PIK3R2 PIK3R3 PLCG2 PRKCD PRKCG PRKCQ PRKCZ PTK2 PTPN1 PTPN11 PTPRC PTPRD PTPRF PTPRU RAD51 ROCK1 RPS6KB1 RPTOR SHC1 SIK2 SOCS1 SOCS3 TRIM72 TUB TYK2 UBC UBTF YWHAB YWHAE YWHAG YWHAZ	97 interacting genes: ABL1 AGTR1 ARL11 ASS1 BCR BRCA1 CBL CCR5 CRLF2 CSF2RB CSF3R CTLA4 CXCR4 DNAJA3 EGFR ELP2 EPOR ERBB2 ERBB3 EZH2 FES FYN GHR GRB10 GRB2 GTF2I H3-4 HES1 HES5 HSFY1 HSPA8 HTR2A IFNGR1 IFNGR2 IGF1R IKBKG IL12RB2 IL23R IL3RA IL4R IL5RA INSR IRS1 IRS2 JAK3 KIT LEPR LYN MAP3K5 MDK MPL MST1R NFKBIA OSMR PDGFRB PIK3R1 PKD1 PLCG2 PPIA PPP1CC PPP2CA PPP2R1B PPP2R5A PRLR PRMT5 PTK2 PTK2B PTPN1 PTPN11 PTPN12 PTPN6 PTPRC RAF1 RBMX SH2B1 SH2B2 SHC1 SIRPA SOCS1 SOCS3 STAM STAM2 STAP2 STAT1 STAT2 STAT3 STAT5A STAT5B TEC TNFRSF1A TRAF6 TSHR TUB UBASH3B VAV1 VCP YES1
Entrez ID		3667	3717
HPRD ID		00943	00993
Ensembl ID		ENSG00000169047	ENSG00000096968
Uniprot IDs		P35568	A8K910 B4DYV1 O60674
PDB IDs		1IRS 1K3A 1QQG 2Z8C 5U1M 6BNT	2B7A 2W1I 2XA4 3E62 3E63 3E64 3FUP 3IO7 3IOK 3JY9 3KCK 3KRR 3LPB 3Q32 3RVG 3TJC 3TJD 3UGC 3ZMM 4AQC 4BBE 4BBF 4C61 4C62 4D0W 4D0X 4D1S 4E4M 4E6D 4E6Q 4F08 4F09 4FVP 4FVQ 4FVR 4GFM 4GMY 4HGE 4IVA 4JI9 4JIA 4P7E 4YTC 4YTF 4YTH 4YTI 4Z32 4ZIM 5AEP 5CF4 5CF5 5CF6 5CF8 5HEZ 5I4N 5L3A 5TQ3 5TQ4 5TQ5 5TQ6 5TQ7 5TQ8 5USY 5USZ 5UT0 5UT1 5UT2 5UT3 5UT4 5UT5 5UT6 5WEV 5WIJ 5WIK 5WIL 5WIM 5WIN 6AAJ 6BBV 6BRW 6BS0 6BSS 6D2I 6DRW 6E2P 6E2Q 6G3C 6M9H 6OAV 6OBB 6OBF 6OBL 6OCC 6TPD
Enriched GO Terms of Interacting Partners?
Tagcloud ?
Tagcloud (Difference) ?
Tagcloud (Intersection) ?