Phosphoinositide 3-Kinase P110 Alpha, P85 Alpha, Bovine (PIK3R1) Active Protein

Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

PIK3R1: regulatory subunit of phosphoinositide-3-kinase. Mediates binding to a subset of tyrosine-phosphorylated proteins through its SH2 domain. Acts as an adapter, mediating the association of the p110 catalytic unit of the alpha, beta and delta enzymes to the plasma membrane, where p110 phosphorylates inositol lipids. May play an additional role in the regulation of the actin cytoskeleton. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Its SH2 domains interacts with the YTHM motif of phosphorylated INSR in vitro. Defects in PIK3R1 are a cause of severe insulin resistance. Four alternatively spliced isoforms have been described.

Protein type: Motility/polarity/chemotaxis; Kinase, lipid; Enzyme, regulatory subunit

Chromosomal Location of Human Ortholog: 5q13.1

Cellular Component: membrane; cytoplasm; plasma membrane; intercellular junction; cytosol; nucleus; phosphoinositide 3-kinase complex

Molecular Function: insulin binding; insulin-like growth factor receptor binding; protein binding; ErbB-3 class receptor binding; neurotrophin TRKA receptor binding; insulin receptor substrate binding; phosphoinositide 3-kinase binding; phosphoinositide 3-kinase regulator activity; transcription factor binding; protein phosphatase binding; transmembrane receptor protein tyrosine kinase adaptor protein activity; insulin receptor binding

Biological Process: negative regulation of osteoclast differentiation; phosphoinositide 3-kinase cascade; nerve growth factor receptor signaling pathway; viral reproduction; positive regulation of RNA splicing; protein amino acid phosphorylation; regulation of phosphoinositide 3-kinase activity; NFAT protein import into nucleus; T cell receptor signaling pathway; positive regulation of glucose import; phosphoinositide phosphorylation; phospholipid metabolic process; positive regulation of transcription factor import into nucleus; epidermal growth factor receptor signaling pathway; platelet activation; fibroblast growth factor receptor signaling pathway; phosphoinositide-mediated signaling; protein stabilization; negative regulation of cell-matrix adhesion; positive regulation of tumor necrosis factor production; DNA damage response, signal transduction resulting in induction of apoptosis; insulin-like growth factor receptor signaling pathway; cellular response to insulin stimulus; induction of apoptosis via death domain receptors; B cell differentiation; T cell costimulation; insulin receptor signaling pathway; phosphatidylinositol biosynthetic process; cell glucose homeostasis; innate immune response; positive regulation of transcription from RNA polymerase II promoter; vascular endothelial growth factor receptor signaling pathway; blood coagulation; leukocyte migration; positive regulation of cell migration; negative regulation of apoptosis

Disease: Agammaglobulinemia 7, Autosomal Recessive; Short Syndrome; Immunodeficiency 36