IRS1

Insulin receptor substrate 1 ;
IRS-1 ;

disease:Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853].,function:May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit.,polymorphism:The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.,PTM:Phosphorylation of Tyr-896 is required for GRB2-binding.,PTM:Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor.,similarity:Contains 1 IRS-type PTB domain.,similarity:Contains 1 PH domain.,subunit:Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR via the PTB domain. Binds to phosphatidylinositol 3-kinase p85 subunit via the phosphorylated YXXM motifs. Binds ROCK1. Binds to UBTF and PIK3CA in nuclear extracts (By similarity). Interacts with SOCS7.,

positive regulation of mesenchymal cell proliferation, regulation of glycogen biosynthetic process, regulation of carbohydrate metabolic process, protein complex assembly, cell surface receptor linked signal transduction, enzyme linked receptor protein signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway,intracellular signaling cascade, protein kinase cascade, positive regulation of cell proliferation, insulin receptor signaling pathway, response to endogenous stimulus, response to hormone stimulus, positive regulation of biosynthetic process, regulation of catabolic process, positive regulation of catabolic process, positive regulation of signal transduction, negative regulation of signal transduction, response to organic substance, regulation of mesenchymal cell proliferation, positive regulation of macromolecule biosynthetic process, regulation of cellular ketone metabolic process, positive regulation of macromolecule metabolic process, positive regulation of cell communication,negative regulation of cell communication, regulation of cellular carbohydrate metabolic process, positive regulation of cellular carbohydrate metabolic process, regulation of glucose transport, positive regulation of glucose transport,regulation of glucose metabolic process, positive regulation of glucose metabolic process, regulation of glucan biosynthetic process, phosphoinositide 3-kinase cascade, regulation of lipid metabolic process, regulation of fatty acid metabolic process, regulation of phosphate metabolic process, regulation of cell migration, positive regulation of cell migration, mammary gland development, positive regulation of cellular biosynthetic process, regulation of cellular catabolic process, positive regulation of cellular catabolic process, regulation of fatty acid beta-oxidation, positive regulation of fatty acid beta-oxidation, response to insulin stimulus, cellular response to insulin stimulus, cellular response to hormone stimulus, regulation of polysaccharide metabolic process, regulation of polysaccharide biosynthetic process, carbohydrate homeostasis, positive regulation of kinase activity, regulation of locomotion,positive regulation of locomotion, regulation of cell proliferation, regulation of phosphorylation, homeostatic process,glucose homeostasis, positive regulation of catalytic activity, regulation of carbohydrate biosynthetic process,response to peptide hormone stimulus, regulation of generation of precursor metabolites and energy, protein kinase B signaling cascade, regulation of kinase activity, regulation of lipid kinase activity, regulation of phosphoinositide 3-kinase activity, positive regulation of phosphoinositide 3-kinase activity, macromolecular complex subunit organization,positive regulation of molecular function, positive regulation of glycogen biosynthetic process, positive regulation of lipid metabolic process, positive regulation of carbohydrate metabolic process, positive regulation of fatty acid metabolic process, regulation of fatty acid oxidation, positive regulation of fatty acid oxidation, regulation of glucose import, positive regulation of glucose import, regulation of insulin receptor signaling pathway, negative regulation of insulin receptor signaling pathway, positive regulation of insulin receptor signaling pathway, insulin-like growth factor receptor signaling pathway, positive regulation of response to stimulus, negative regulation of response to stimulus,gland development, chemical homeostasis, regulation of lipid catabolic process, positive regulation of lipid catabolic process, positive regulation of transport, regulation of phosphorus metabolic process, protein oligomerization,regulation of cell motion, positive regulation of cell motion, protein heterooligomerization, regulation of transferase activity, positive regulation of transferase activity, macromolecular complex assembly, protein complex biogenesis,