The following text describes a protein:
Function:
Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (By similarity). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (By similarity). In contrast to mTORC1, mTORC2 is nutrient-insensitive (By similarity). Within the mTORC2 complex, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR (By similarity). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (By similarity). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (By similarity). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (By similarity). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (By similarity). Inhibits HRAS and KRAS independently of mTORC2 complex (By similarity). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (By similarity). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (By similarity).
Subcellular Localization:
Cell membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Early endosome membrane; Peripheral membrane protein. Late endosome membrane; Peripheral membrane protein. Lysosome membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein. Mitochondrion outer membrane; Peripheral membrane protein. Cytoplasm, perinuclear region. Nucleus. Note=The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane, lysosomes and perinuclear region. Iin lysosomal membrane, mTORC2 is sensitive to lysosomal positioning in the cell (By similarity). Following phosphorylation by PKC, localizes to the perinuclear region, where the mTORC2 complexe specifically phosphorylates SGK1, but not AKT (By similarity).
Domain:
The CRIM domain forms a ubiquitin-like fold with a characteristic acidic loop, which recognizes and binds AGC protein kinase family members substrates; The SIN1-type PH binds phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). It plays a dual role in mTORC2: in absence of PI(3,4,5)P3, it binds and inactivates MTOR. PI(3,4,5)P3-binding relieves the inhibition, leading to mTORC2 activation.
Sequence:
MAFLDNPTIILAHIRQSHVTSDDTGMCEMVLIDHDVDLEKTHPPSVPGDSGSEVQGSSGETQGYIYAQSVDITSSWDFGIRRRSNTAQRLERLRKERQNQIKCKNIQWKERNSKQSAQELKSLFEKKSLKEKPPSSGKQSILSVRLEQCPLQLNNPFNEYSKFDGKGHVGTTATKKIDVYLPLHSSQDRLLPMTVVTMASARVQDLIGLICWQYTSEGREPKLNDNVSAYCLHIAEDDGEVDTDFPPLDSNEPIHKFGFSTLALVEKYSSPGLTSKESLFVRINAAHGFSLIQVDNTKVTMKEILLKALKRRKGSQKISGPQYRLEKQSEPNIGVDLESTLESQNAWEFCLVRENSSRADGVFEEDSQIDIATVQDMLSSHHYKSFKVSMIHRLRFTTDVQLGISGDKVEIDPVTNQKASTKFWIKQKPISIDCDLLCACDLAEEKSPSHAVFKLTYLSSHDYKHLYFESDAATVSEIVLKVNYILESRASTARADYFAQKQRKLNRRTSFSFQKEKKSGQQ