IRS2 and PTPN11

Data Source:
HPRD (in vivo)

		IRS2	PTPN11
Description		insulin receptor substrate 2	protein tyrosine phosphatase non-receptor type 11
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GO Annotations	Cellular Component	Cytosol Plasma Membrane Protein-containing Complex	Nucleus Nucleoplasm Cytoplasm Mitochondrion Cytosol Protein-containing Complex
	Molecular Function	Insulin Receptor Binding Protein Binding Protein Kinase Binding Protein Phosphatase Binding Protein Domain Specific Binding Phosphatidylinositol 3-kinase Binding 14-3-3 Protein Binding	Phosphotyrosine Residue Binding Phosphoprotein Phosphatase Activity Protein Tyrosine Phosphatase Activity Non-membrane Spanning Protein Tyrosine Phosphatase Activity Insulin Receptor Binding Protein Binding Protein Kinase Binding Protein Domain Specific Binding Signaling Receptor Complex Adaptor Activity Receptor Tyrosine Kinase Binding D1 Dopamine Receptor Binding Phospholipase Binding Insulin Receptor Substrate Binding Cadherin Binding Cell Adhesion Molecule Binding Peptide Hormone Receptor Binding Protein Tyrosine Kinase Binding
	Biological Process	MAPK Cascade Positive Regulation Of Mesenchymal Cell Proliferation Negative Regulation Of B Cell Apoptotic Process Glucose Metabolic Process Signal Transduction Axon Guidance Brain Development Positive Regulation Of Cell Population Proliferation Insulin Receptor Signaling Pathway Response To Glucose Negative Regulation Of Long-chain Fatty Acid Import Across Plasma Membrane Positive Regulation Of Glucose Metabolic Process Positive Regulation Of Phosphatidylinositol 3-kinase Signaling Regulation Of Lipid Metabolic Process Positive Regulation Of Cell Migration Mammary Gland Development Positive Regulation Of B Cell Proliferation Positive Regulation Of Fatty Acid Beta-oxidation Positive Regulation Of Insulin Secretion Cellular Response To Insulin Stimulus Negative Regulation Of Kinase Activity Interleukin-7-mediated Signaling Pathway Positive Regulation Of Glycogen Biosynthetic Process Positive Regulation Of Glucose Import Positive Regulation Of Ras Protein Signal Transduction Phosphatidylinositol-mediated Signaling Positive Regulation Of Protein Kinase B Signaling Lipid Homeostasis Cellular Response To Glucose Stimulus	DNA Damage Checkpoint Activation Of MAPK Activity Triglyceride Metabolic Process Epidermal Growth Factor Receptor Signaling Pathway Integrin-mediated Signaling Pathway Axon Guidance Brain Development Heart Development Fibroblast Growth Factor Receptor Signaling Pathway Hormone-mediated Signaling Pathway Cytokine-mediated Signaling Pathway Cerebellar Cortex Formation Platelet Activation Platelet Formation T Cell Costimulation Negative Regulation Of Chondrocyte Differentiation Microvillus Organization Positive Regulation Of Interferon-beta Production Positive Regulation Of Interleukin-6 Production Positive Regulation Of Tumor Necrosis Factor Production Abortive Mitotic Cell Cycle Regulation Of Cell Adhesion Mediated By Integrin Negative Regulation Of Cell Adhesion Mediated By Integrin Multicellular Organism Growth Organ Growth Peptidyl-tyrosine Dephosphorylation Megakaryocyte Development Atrioventricular Canal Development ERBB Signaling Pathway Hormone Metabolic Process Glucose Homeostasis Regulation Of Protein-containing Complex Assembly Positive Regulation Of Ossification Positive Regulation Of Mitotic Cell Cycle Positive Regulation Of Glucose Import Positive Regulation Of Insulin Receptor Signaling Pathway Negative Regulation Of Insulin Secretion Regulation Of Protein Export From Nucleus Positive Regulation Of Hormone Secretion Platelet-derived Growth Factor Receptor Signaling Pathway Neurotrophin TRK Receptor Signaling Pathway Ephrin Receptor Signaling Pathway Multicellular Organismal Reproductive Process Genitalia Development Inner Ear Development Homeostasis Of Number Of Cells Within A Tissue Positive Regulation Of Peptidyl-tyrosine Phosphorylation Leukocyte Migration Negative Regulation Of Cortisol Secretion Positive Regulation Of Protein Kinase B Signaling Bergmann Glial Cell Differentiation Negative Regulation Of Growth Hormone Secretion Face Morphogenesis Regulation Of Type I Interferon-mediated Signaling Pathway Intestinal Epithelial Cell Migration Interleukin-6-mediated Signaling Pathway Positive Regulation Of ERK1 And ERK2 Cascade Cellular Response To Mechanical Stimulus Cellular Response To Cytokine Stimulus Cellular Response To Epidermal Growth Factor Stimulus
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 RET signaling Signaling by Erythropoietin 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 Growth hormone receptor signaling	Interleukin-6 signaling PI3K Cascade MAPK3 (ERK1) activation MAPK1 (ERK2) activation GPVI-mediated activation cascade Prolactin receptor signaling PIP3 activates AKT signaling Spry regulation of FGF signaling Signaling by SCF-KIT GAB1 signalosome Downstream signal transduction PECAM1 interactions Tie2 Signaling Constitutive Signaling by Aberrant PI3K in Cancer Signaling by Leptin Costimulation by the CD28 family CTLA4 inhibitory signaling PD-1 signaling Signal regulatory protein family interactions Netrin mediated repulsion signals Platelet sensitization by LDL Interleukin-3, Interleukin-5 and GM-CSF signaling Interleukin-3, Interleukin-5 and GM-CSF signaling PI-3K cascade:FGFR1 FRS-mediated FGFR1 signaling PI-3K cascade:FGFR2 FRS-mediated FGFR2 signaling FRS-mediated FGFR3 signaling PI-3K cascade:FGFR3 FRS-mediated FGFR4 signaling PI-3K cascade:FGFR4 Negative regulation of FGFR1 signaling Negative regulation of FGFR2 signaling Negative regulation of FGFR3 signaling Negative regulation of FGFR4 signaling PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling Regulation of IFNG signaling RET signaling Interleukin-20 family signaling MET activates PTPN11 Regulation of RUNX1 Expression and Activity Interleukin-37 signaling Activated NTRK2 signals through FRS2 and FRS3 Interferon alpha/beta signaling Regulation of IFNA signaling Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon FLT3 Signaling STAT5 Activation STAT5 activation downstream of FLT3 ITD mutants Signaling by FLT3 ITD and TKD mutants
Drugs			Dodecyltrimethylammonium
Diseases			Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noonan syndrome-like with loose anagen hair (NS/LAH); CBL-mutation associated syndrome (CBL); Neurofibromatosis type 1 (NF1); Neurofibromatosis type 2 (NF2); Neurofibromatosis-Noonan syndrome (NFNS); Legius syndrome; Cardiofaciocutaneous syndrome (CFCS); Costello syndrome (CS) Metachondromatosis
GWAS		Antipsychotic drug-induced weight gain in schizophrenia ( 31447353) Heel bone mineral density ( 30598549 28869591) Hematocrit ( 32888494) Hemoglobin ( 32888494) Hemoglobin levels ( 32327693) High light scatter reticulocyte count ( 32888494) Insulin-related traits (multivariate analysis) ( 32002517) Mean corpuscular hemoglobin ( 29403010 32888494 27863252) Mean corpuscular volume ( 29403010 32888494 27863252) Mean reticulocyte volume ( 32888494) Mean spheric corpuscular volume ( 32888494) Nose size ( 27182965) Paclitaxel disposition in epithelial ovarian cancer ( 29367611) Platelet count ( 29403010) Prostate cancer ( 29117387) Red cell distribution width ( 32888494) Reticulocyte count ( 32888494) Reticulocyte fraction of red cells ( 32888494 27863252) Type 2 diabetes ( 30297969) Vertical cup-disc ratio (multi-trait analysis) ( 31959993) White matter lesion progression ( 26451028) White matter lesion progression (adjusted for white matter lesion burden at baseline) ( 26451028)	Alcohol consumption (max-drinks) ( 29460428) Alcohol dependence symptom count ( 29460428) Apolipoprotein A1 levels ( 32203549) Blood pressure ( 21572416) Body mass index ( 26426971) Diastolic blood pressure ( 26390057) Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test) ( 29455858) Diastolic blood pressure x smoking status (ever vs never) interaction (2df test) ( 29455858) HDL cholesterol levels ( 32203549) Hematological parameters ( 19820697) Hypothyroidism ( 22493691) Low HDL-cholesterol levels ( 31006500) Mean arterial pressure ( 27618448) Medication use (agents acting on the renin-angiotensin system) ( 31015401) Medication use (beta blocking agents) ( 31015401) Medication use (diuretics) ( 31015401) Medication use (thyroid preparations) ( 31015401) Multiple sclerosis ( 31604244) Peripheral artery disease ( 31285632) Platelet count ( 22139419 32888494) Reaction time ( 29844566) Response to alcohol consumption (flushing response) ( 29460428) Retinal vascular caliber ( 21060863) Rheumatoid arthritis ( 30423114 24390342) Systemic seropositive rheumatic diseases (Systemic sclerosis or systemic lupus erythematosus or rheumatoid arthritis or idiopathic inflammatory myopathies) ( 30573655) Systolic blood pressure ( 26390057 30578418) Systolic blood pressure x smoking status (current vs non-current) interaction (2df test) ( 29455858) Systolic blood pressure x smoking status (ever vs never) interaction (2df test) ( 29455858) Tetralogy of Fallot ( 23297363) Type 1 diabetes ( 17554300) Urate levels ( 23263486)
Interacting Genes		40 interacting genes: ATP2A1 ATP2A2 BCL2L1 CRK EPOR FES GRB2 IGF1R IL4R INSR JAK1 JAK2 JAK3 MPL MTDH NEDD4 NTRK1 PIK3CA PIK3CD PIK3R1 PIK3R2 PIK3R3 PLCG1 PTPN11 PTPN6 PTPRF RPTOR SHC1 SOCS1 SOCS3 SOCS6 SOCS7 SRPK2 TYK2 UBTF YWHAB YWHAE YWHAG YWHAQ YWHAZ	166 interacting genes: AATK ACTN4 AKT1 AR ARHGAP1 AXL BCR BDKRB2 BEX1 BEX2 BLZF1 BTLA CALR CAT CAV1 CBL CCKBR CD33 CDH5 CEACAM1 CHUK CRKL CSF2RB CSF3R CTDSP1 CTLA4 CXCR4 DAB1 DDR1 DMRTC1 EGFR EPHA1 EPHA2 EPOR ERBB2 ERBB3 ERBB4 FAM71E1 FBXW7 FCGR1B FCGR2B FCRL3 FGFR2 FGFR4 FLT1 FLT3 FLT4 FRS2 FRS3 FYN GAB1 GAB2 GAB3 GHR GMNN GOLGA2 GRB2 GRIN2B GTF2A2 HNRNPU HSP90B1 HSPA5 HSPA9 HSPD1 IFNAR1 IFNGR1 IGF1R IL4R IL6ST ILK INPP5D INSR IRS1 IRS2 IRS4 JAK1 JAK2 KDR KIR2DL5A KIT KLRC1 LAIR1 LCK LEPR LIFR LILRB4 LINC01558 LINC02907 LNX1 LRP1 MAP3K4 MAP3K5 MAPK3 MAPT MET MPIG6B MPL MPZL1 MS4A2 MVP NEB NEDD9 NOX4 NSUN5 NSUN5P2 NTRK1 NTRK2 ORMDL3 PAG1 PDGFRA PDGFRB PECAM1 PIK3CA PIK3CG PIK3R1 PILRA PILRB PLCG1 PNCK POU2AF1 PRKCA PRKCB PRKCH PRLR PTK2 PTK2B PTK7 PTPN6 PXN RANGRF RET ROR2 ROS1 RPIA SELE SERF2 SERPINF1 SHC1 SIGLEC11 SIGLEC12 SIGLEC7 SIRPA SIT1 SLAMF1 SLAMF6 SLC38A1 SLN SOCS3 SOS1 SPRY2 SRC SRSF10 STAT1 STAT3 STAT5A STAT5B SYNCRIP TEK TIE1 TLK1 TNFRSF1A TREML1 TRIM32 TRMT2B TSC2 TXNIP
Entrez ID		8660	5781
HPRD ID		02878	01470
Ensembl ID		ENSG00000185950	ENSG00000179295
Uniprot IDs		Q9P084 Q9Y4H2	Q06124
PDB IDs		3FQW 3FQX	2SHP 3B7O 3MOW 3O5X 3TKZ 3TL0 3ZM0 3ZM1 3ZM2 3ZM3 4DGP 4DGX 4GWF 4H1O 4H34 4JE4 4JEG 4JMG 4NWF 4NWG 4OHD 4OHE 4OHH 4OHI 4OHL 4PVG 4QSY 4RDD 5BK8 5DF6 5EHP 5EHR 5I6V 5IBM 5IBS 5X7B 5X94 5XZR 6ATD 6BMR 6BMU 6BMV 6BMW 6BMX 6BMY 6BN5 6CMP 6CMQ 6CMR 6CMS 6CRF 6CRG 6IHZ 6MD7 6MD9 6MDA 6MDB 6MDC 6MDD 6R5G 7JVM 7JVN
Enriched GO Terms of Interacting Partners?
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