FBXW8 and IRS1

Data Source:
BioGRID (enzymatic study)

		FBXW8	IRS1
Description		F-box and WD repeat domain containing 8	insulin receptor substrate 1
Image		No pdb structure
GO Annotations	Cellular Component	Golgi Apparatus Cytosol SCF Ubiquitin Ligase Complex Cul7-RING Ubiquitin Ligase Complex Perinuclear Region Of Cytoplasm 3M Complex	Nucleus Nucleoplasm Cytoplasm Cytosol Plasma Membrane Insulin Receptor Complex Caveola Intracellular Membrane-bounded Organelle
	Molecular Function	Ubiquitin-protein Transferase Activity Protein Binding	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	Protein Polyubiquitination Golgi Organization Cell Population Proliferation Protein Ubiquitination Post-translational Protein Modification Positive Regulation Of Dendrite Morphogenesis Labyrinthine Layer Blood Vessel Development Positive Regulation Of Transcription Factor Catabolic 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
Pathways		Neddylation Antigen processing: Ubiquitination & Proteasome degradation	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			[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID
Diseases
GWAS		Brain morphology (MOSTest) ( 32665545) Brain structure ( 22504417) Dentate gyrus granule cell layer volume ( 30279459) Dentate gyrus molecular layer volume ( 30279459) HATA volume ( 30279459) Hippocampal subfield CA1 volume ( 30279459) Hippocampal subfield CA3 volume ( 30279459) Hippocampal subfield CA4 volume ( 30279459) Hippocampal tail volume ( 30279459) Marginal zone lymphoma or rheumatoid arthritis ( 31407831) Subiculum volume ( 30279459) Total hippocampal volume ( 30279459)	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		6 interacting genes: CUL7 IRS1 MYC RBX1 SKP1 UBE2D3	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		26259	3667
HPRD ID		16427	00943
Ensembl ID		ENSG00000174989	ENSG00000169047
Uniprot IDs		Q8N3Y1	P35568
PDB IDs			1IRS 1K3A 1QQG 2Z8C 5U1M 6BNT
Enriched GO Terms of Interacting Partners?
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