Protein: Target of rapamycin complex 2 subunit MAPKAP1 (TORC2 subunit MAPKAP1) (Mitogen-activated protein kinase 2-associated protein 1) (Stress-activated map kinase-interacting protein 1) (SAPK-interacting protein 1) (mSIN1) (Q9BPZ7)
Organism: Homo sapiens (Human)
Function: Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. 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 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex.
Subcellular location: Cell membrane {ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:21867682}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Early endosome membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Late endosome membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Lysosome membrane {ECO:0000269|PubMed:31130364}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Golgi apparatus membrane {ECO:0000269|PubMed:17303383}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Mitochondrion outer membrane {ECO:0000269|PubMed:28143890}; Peripheral membrane protein {ECO:0000269|PubMed:17303383}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:30837283}. Nucleus {ECO:0000269|PubMed:26263164}. Note=The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane, lysosomes and perinuclear region (PubMed:17303383, PubMed:21867682, PubMed:30837283). Iin lysosomal membrane, mTORC2 is sensitive to lysosomal positioning in the cell (PubMed:31130364). Following phosphorylation by PKC, localizes to the perinuclear region, where the mTORC2 complexe specifically phosphorylates SGK1, but not AKT (PubMed:30837283). {ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21867682, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:31130364}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane {ECO:0000269|PubMed:26263164}. Cytoplasm, cytosol {ECO:0000269|PubMed:26263164}.; SUBCELLULAR LOCATION: [Isoform 6]: Cytoplasm {ECO:0000269|PubMed:26263164}. Nucleus {ECO:0000269|PubMed:26263164}.
Interaction partners:
- Proline-rich protein 5
- Target of rapamycin complex subunit LST8
- DEP domain-containing mTOR-interacting protein
- Rapamycin-insensitive companion of mTOR
- Serine/threonine-protein kinase mTOR
- Proline-rich protein 5-like
- Proline-rich AKT1 substrate 1
- TELO2-interacting protein 1 homolog
- Regulatory-associated protein of mTOR
- RAC-alpha serine/threonine-protein kinase
Sequence:
MAFLDNPTIILAHIRQSHVTSDDTGMCEMVLIDHDVDLEKIHPPSMPGDSGSEIQGSNGETQGYVYAQSVDITSSWDFGIRRRSNTAQRLERLRKERQNQIKCKNIQWKERNSKQSAQELKSLFEKKSLKEKPPISGKQSILSVRLEQCPLQLNNPFNEYSKFDGKGHVGTTATKKIDVYLPLHSSQDRLLPMTVVTMASARVQDLIGLICWQYTSEGREPKLNDNVSAYCLHIAEDDGEVDTDFPPLDSNEPIHKFGFSTLALVEKYSSPGLTSKESLFVRINAAHGFSLIQVDNTKVTMKEILLKAVKRRKGSQKVSGPQYRLEKQSEPNVAVDLDSTLESQSAWEFCLVRENSSRADGVFEEDSQIDIATVQDMLSSHHYKSFKVSMIHRLRFTTDVQLGISGDKVEIDPVTNQKASTKFWIKQKPISIDSDLLCACDLAEEKSPSHAIFKLTYLSNHDYKHLYFESDAATVNEIVLKVNYILESRASTARADYFAQKQRKLNRRTSFSFQKEKKSGQQ