Sin1: a member of a conserved family of proteins that have an essential roles in signal transduction from yeast to mammals. An essential component of the mTORC2 complex, which consists of mTOR, LST8, Sin1, Protor (PRR5), and RICTOR, the Rapamycin Insensitive Companion of mTOR. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 regulates the phosphorylation of SGK1 S422 and PKCA S657. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Contains a Ras-binding (RBD) and a pleckstrin homology (PH) domains. Plays an important role in the SAPK signaling pathway by binding directly to both ATF-2 and p38. A genetic knockout of Sin1 abolished Akt-S473 phosphorylation and disrupts the RICTOR-mTOR interaction, but Akt-Thr308 phosphorylation is maintained. Six alternatively-spliced isoforms of the human protein have been reported. All isoforms except 4 can be incorporated into the the mTORC2 complex.
Protein type: Adaptor/scaffold
Chromosomal Location of Human Ortholog: 9q33.3
Cellular Component: nucleoplasm; Golgi apparatus; cytoplasm; cytoplasmic membrane-bound vesicle; plasma membrane; nucleus; cytosol
Molecular Function: protein binding; phosphatidylinositol-4,5-bisphosphate binding; Ras GTPase binding; phosphatidylinositol-3,4,5-triphosphate binding; phosphatidylinositol-3,4-bisphosphate binding; protein kinase binding
Biological Process: epidermal growth factor receptor signaling pathway; substantia nigra development; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; nerve growth factor receptor signaling pathway; T cell costimulation; negative regulation of Ras protein signal transduction; innate immune response; vascular endothelial growth factor receptor signaling pathway
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