PIK3R1 and IRS1

Data Source:
HPRD (in vivo, in vitro)

		PIK3R1	IRS1
Description		phosphoinositide-3-kinase regulatory subunit 1	insulin receptor substrate 1
Image
GO Annotations	Cellular Component	Nucleus Cytoplasm Cis-Golgi Network Cytosol Plasma Membrane Cell-cell Junction Phosphatidylinositol 3-kinase Complex Phosphatidylinositol 3-kinase Complex, Class IA Membrane Perinuclear Region Of Cytoplasm Perinuclear Endoplasmic Reticulum Membrane	Nucleus Nucleoplasm Cytoplasm Cytosol Plasma Membrane Insulin Receptor Complex Caveola Intracellular Membrane-bounded Organelle
	Molecular Function	Phosphotyrosine Residue Binding Transmembrane Receptor Protein Tyrosine Kinase Adaptor Activity Insulin Receptor Binding Insulin-like Growth Factor Receptor Binding Neurotrophin TRKA Receptor Binding Protein Binding Transcription Factor Binding Protein Phosphatase Binding Phosphatidylinositol 3-kinase Regulator Activity Phosphatidylinositol 3-kinase Regulatory Subunit Binding ErbB-3 Class Receptor Binding Phosphatidylinositol 3-kinase Binding Insulin Binding Insulin Receptor Substrate Binding 1-phosphatidylinositol-3-kinase Regulator Activity Protein Heterodimerization Activity	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
	Biological Process	Cellular Glucose Homeostasis Negative Regulation Of Cell-matrix Adhesion Protein Phosphorylation Protein Import Into Nucleus Phosphatidylinositol Biosynthetic Process Epidermal Growth Factor Receptor Signaling Pathway G Protein-coupled Receptor Signaling Pathway Axon Guidance Insulin Receptor Signaling Pathway Extrinsic Apoptotic Signaling Pathway Via Death Domain Receptors Intrinsic Apoptotic Signaling Pathway In Response To DNA Damage Positive Regulation Of Lamellipodium Assembly Phosphatidylinositol 3-kinase Signaling Positive Regulation Of Phosphatidylinositol 3-kinase Signaling Viral Process Cytokine-mediated Signaling Pathway Platelet Activation B Cell Differentiation Positive Regulation Of Cell Migration T Cell Costimulation Positive Regulation Of Tumor Necrosis Factor Production Cellular Response To Insulin Stimulus Positive Regulation Of RNA Splicing Substrate Adhesion-dependent Cell Spreading Cellular Response To UV Response To Endoplasmic Reticulum Stress Fc-epsilon Receptor Signaling Pathway Fc-gamma Receptor Signaling Pathway Involved In Phagocytosis ERBB2 Signaling Pathway Positive Regulation Of Protein Import Into Nucleus Negative Regulation Of Apoptotic Process Regulation Of Phosphatidylinositol 3-kinase Activity Negative Regulation Of Osteoclast Differentiation Positive Regulation Of Transcription By RNA Polymerase II Positive Regulation Of Glucose Import Regulation Of Insulin Receptor Signaling Pathway Phosphatidylinositol Phosphorylation Insulin-like Growth Factor Receptor Signaling Pathway Vascular Endothelial Growth Factor Receptor Signaling Pathway Phosphatidylinositol-mediated Signaling Protein Stabilization T Cell Receptor Signaling Pathway Leukocyte Migration Positive Regulation Of Filopodium Assembly Negative Regulation Of Stress Fiber Assembly Positive Regulation Of Protein Kinase B Signaling Growth Hormone Receptor Signaling Pathway Positive Regulation Of Focal Adhesion Disassembly Positive Regulation Of Endoplasmic Reticulum Unfolded Protein Response Positive Regulation Of Protein Localization To Plasma Membrane	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
Pathways		PI3K Cascade IRS-mediated signalling GPVI-mediated activation cascade Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants PI3K events in ERBB4 signaling PIP3 activates AKT signaling Interleukin-7 signaling Interleukin-7 signaling Signaling by SCF-KIT Synthesis of PIPs at the plasma membrane GAB1 signalosome Signaling by cytosolic FGFR1 fusion mutants Downstream signal transduction PI3K events in ERBB2 signaling PI3K/AKT activation Downstream TCR signaling Role of phospholipids in phagocytosis Tie2 Signaling Constitutive Signaling by Aberrant PI3K in Cancer DAP12 signaling Role of LAT2/NTAL/LAB on calcium mobilization Nephrin family interactions Costimulation by the CD28 family CD28 dependent PI3K/Akt signaling G alpha (q) signalling events GP1b-IX-V activation signalling VEGFA-VEGFR2 Pathway VEGFA-VEGFR2 Pathway Interleukin-3, Interleukin-5 and GM-CSF signaling Constitutive Signaling by EGFRvIII PI-3K cascade:FGFR1 PI-3K cascade:FGFR2 PI-3K cascade:FGFR3 PI-3K cascade:FGFR4 Signaling by FGFR2 in disease Signaling by FGFR4 in disease Signaling by FGFR1 in disease RAF/MAP kinase cascade Interleukin-4 and Interleukin-13 signaling PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling MET activates PI3K/AKT signaling Signaling by FGFR3 fusions in cancer Signaling by FGFR3 point mutants in cancer RET signaling Extra-nuclear estrogen signaling Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Activated NTRK2 signals through PI3K Interleukin receptor SHC signaling Regulation of signaling by CBL Regulation of signaling by CBL Activated NTRK3 signals through PI3K FLT3 Signaling FLT3 Signaling Signaling by ERBB2 KD Mutants Signaling by ERBB2 ECD mutants Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants Signaling by PDGFRA extracellular domain mutants Signaling by FLT3 fusion proteins Signaling by FLT3 fusion proteins Signaling by FLT3 ITD and TKD mutants Signaling by FLT3 ITD and TKD mutants Antigen activates B Cell Receptor (BCR) leading to generation of second messengers Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	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
Drugs		Isoprenaline SF1126 Enzastaurin Wortmannin	[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID
Diseases
GWAS		Alzheimer's disease biomarkers ( 23419831) Anthropometric traits (multi-trait analysis) ( 30166351) Birth weight ( 31043758) Bone mineral density (hip) ( 26911590) Cleft lip with or without cleft palate ( 28054174) Corneal astigmatism ( 30306274) Crohn's disease ( 32581322) Estimated glomerular filtration rate ( 31152163 30604766) Glomerular filtration rate (creatinine) ( 28452372 26831199) HDL cholesterol levels ( 32203549) Height ( 31562340) Hip minimal joint space width ( 27701424) Intelligence (MTAG) ( 29326435) Mean corpuscular hemoglobin ( 32888494 27863252) Mean corpuscular volume ( 32888494 27863252) Mean reticulocyte volume ( 32888494) Menarche (age at onset) ( 23599027) Offspring birth weight ( 31043758) Red cell distribution width ( 32888494 27863252) Rosacea symptom severity ( 29771307) Triglyceride levels ( 29083408 32203549) Type 2 diabetes (adjusted for BMI) ( 30297969)	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)
Interacting Genes		175 interacting genes: ABL1 ADAM12 ADAMTS2 AGAP2 AKT1 ALK ANK3 APPL1 AR ARAF ARHGAP1 ARHGAP17 ARHGAP32 AXL BCAR1 BLK BRCA1 CBL CBLB CCL14 CD19 CD22 CD28 CD2AP CD3E CD4 CD40 CD5 CD7 CDC42 CDH2 CHRNA7 CLNK CRK CRKL CSF1R CSF2RA CTLA4 CTNNB1 CXCL2 CYP4A11 DLX2 DNM1 DOK1 EGF EGFR ENKUR EPHA2 EPOR ERAS ERBB2 ERBB3 ERBB4 ESR1 EZR FASLG FCGR2A FER FES FGFR1 FLT1 FYN GAB1 GAB2 GAB3 GHR GP1BA GRB2 GSPT1 GTF2H1 HCK HCST HGS HOXA1 HRAS HTT IFNAR1 IGF1R IKZF3 IL13 IL1R1 IL1RAP IL2RB IL7R INPP4A INSR IRS1 IRS2 IRS4 ITSN1 JAK1 JAK2 JAK3 KBTBD2 KHDRBS1 KIT LAT LCK LNX2 LRRK2 MAPK8 MAPT MET MME MST1R MYO16 NFKBIA NTRK1 NTRK2 NUP85 NYAP1 NYAP2 PASK PDE4D PDGFB PDGFRA PDGFRB PECAM1 PFN1 PIK3AP1 PIK3CA PIK3CB PIK3CD PPM1A PRMT8 PROM1 PSEN1 PSMB5 PTK2 PTK2B PTPN11 PTPN6 RAC1 RASA1 RASD2 RB1 RET RRAS2 SH3KBP1 SHB SHC1 SLC9A2 SOCS1 SOCS6 SOCS7 SQSTM1 SRC SSTR2 STAT3 SYK SYN1 TEC TEK TGFBR1 TGFBR2 TIE1 TLR2 TNS4 TOM1L1 TRAT1 TSHR TTR TUB TUBA1B TUBG1 TXK TYK2 TYRO3 VAV1 VAV3 WAS WASF3 WBP11 YWHAG YWHAZ	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
Entrez ID		5295	3667
HPRD ID		01381	00943
Ensembl ID		ENSG00000145675	ENSG00000169047
Uniprot IDs		A0A2X0SFG1 P27986	P35568
PDB IDs		1A0N 1AZG 1H9O 1PBW 1PHT 1PIC 1PKS 1PKT 2IUG 2IUH 2IUI 2RD0 2V1Y 3HHM 3HIZ 3I5R 3I5S 4A55 4JPS 4L1B 4L23 4L2Y 4OVU 4OVV 4WAF 4YKN 4ZOP 5AUL 5FI4 5GJI 5ITD 5M6U 5SW8 5SWG 5SWO 5SWP 5SWR 5SWT 5SX8 5SX9 5SXA 5SXB 5SXC 5SXD 5SXE 5SXF 5SXI 5SXJ 5SXK 5UBT 5UK8 5UKJ 5UL1 5VLR 5XGH 5XGI 5XGJ 6NCT 6PYR 6PYU	1IRS 1K3A 1QQG 2Z8C 5U1M 6BNT
Enriched GO Terms of Interacting Partners?
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