Protein: Regulatory-associated protein of mTOR (Raptor) (p150 target of rapamycin (TOR)-scaffold protein) (Q8N122)
Organism: Homo sapiens (Human)
Function: Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis. mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD) (By similarity).
Subcellular location: Lysosome membrane {ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764}. Cytoplasm {ECO:0000269|PubMed:20381137}. Cytoplasmic granule {ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:25940091}. Note=Targeting to lysosomes depends on amino acid availability: recruited to lysosome membranes via interaction with GTP-bound form of RagA/RRAGA (or RagB/RRAGB) in complex with the GDP-bound form of RagC/RRAGC (or RagD/RRAGD), promoting recruitment of mTORC1 to the lysosomes (PubMed:31601708, PubMed:31601764). In arsenite-stressed cells, accumulates in stress granules when associated with SPAG5 and association with lysosomes is drastically decreased (PubMed:23953116). {ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764}.
Sequence: MESEMLQSPLLGLGEEDEADLTDWNLPLAFMKKRHCEKIEGSKSLAQSWRMKDRMKTVSVALVLCLNVGVDPPDVVKTTPCARLECWIDPLSMGPQKALETIGANLQKQYENWQPRARYKQSLDPTVDEVKKLCTSLRRNAKEERVLFHYNGHGVPRPTVNGEVWVFNKNYTQYIPLSIYDLQTWMGSPSIFVYDCSNAGLIVKSFKQFALQREQELEVAAINPNHPLAQMPLPPSMKNCIQLAACEATELLPMIPDLPADLFTSCLTTPIKIALRWFCMQKCVSLVPGVTLDLIEKIPGRLNDRRTPLGELNWIFTAITDTIAWNVLPRDLFQKLFRQDLLVASLFRNFLLAERIMRSYNCTPVSSPRLPPTYMHAMWQAWDLAVDICLSQLPTIIEEGTAFRHSPFFAEQLTAFQVWLTMGVENRNPPEQLPIVLQVLLSQVHRLRALDLLGRFLDLGPWAVSLALSVGIFPYVLKLLQSSARELRPLLVFIWAKILAVDSSCQADLVKDNGHKYFLSVLADPYMPAEHRTMTAFILAVIVNSYHTGQEACLQGNLIAICLEQLNDPHPLLRQWVAICLGRIWQNFDSARWCGVRDSAHEKLYSLLSDPIPEVRCAAVFALGTFVGNSAERTDHSTTIDHNVAMMLAQLVSDGSPMVRKELVVALSHLVVQYESNFCTVALQFIEEEKNYALPSPATTEGGSLTPVRDSPCTPRLRSVSSYGNIRAVATARSLNKSLQNLSLTEESGGAVAFSPGNLSTSSSASSTLGSPENEEHILSFETIDKMRRASSYSSLNSLIGVSFNSVYTQIWRVLLHLAADPYPEVSDVAMKVLNSIAYKATVNARPQRVLDTSSLTQSAPASPTNKGVHIHQAGGSPPASSTSSSSLTNDVAKQPVSRDLPSGRPGTTGPAGAQYTPHSHQFPRTRKMFDKGPEQTADDADDAAGHKSFISATVQTGFCDWSARYFAQPVMKIPEEHDLESQIRKEREWRFLRNSRVRRQAQQVIQKGITRLDDQIFLNRNPGVPSVVKFHPFTPCIAVADKDSICFWDWEKGEKLDYFHNGNPRYTRVTAMEYLNGQDCSLLLTATDDGAIRVWKNFADLEKNPEMVTAWQGLSDMLPTTRGAGMVVDWEQETGLLMSSGDVRIVRIWDTDREMKVQDIPTGADSCVTSLSCDSHRSLIVAGLGDGSIRVYDRRMALSECRVMTYREHTAWVVKASLQKRPDGHIVSVSVNGDVRIFDPRMPESVNVLQIVKGLTALDIHPQADLIACGSVNQFTAIYNSSGELINNIKYYDGFMGQRVGAISCLAFHPHWPHLAVGSNDYYISVYSVEKRVR
InterPro domains: - IPR016024: Armadillo-type fold (homologous_superfamily) [391-847]
- IPR001680: WD40 repeat (repeat) [1012-1329]
- IPR000357: HEAT repeat (repeat) [558-627]
- IPR015943: WD40/YVTN repeat-like-containing domain superfamily (homologous_superfamily) [1006-1334]
- IPR004083: Regulatory associated protein of TOR (family) [16-1329]
- IPR011989: Armadillo-like helical (homologous_superfamily) [442-693]
- IPR029347: Raptor, N-terminal CASPase-like domain (domain) [54-207]
- IPR036322: WD40-repeat-containing domain superfamily (homologous_superfamily) [1018-1331]
Interaction partners: - Ragulator complex protein LAMTOR4
- Proline-rich AKT1 substrate 1
- Ras-related GTP-binding protein A
- Ras-related GTP-binding protein B
- GTP-binding protein Rheb
- Ribosomal protein S6 kinase beta-1
- Serine/threonine-protein kinase mTOR
- Peptidyl-prolyl cis-trans isomerase FKBP1A
- Ras-related GTP-binding protein C
- DEP domain-containing mTOR-interacting protein
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0051703 (biological process involved in intraspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065008 (regulation of biological quality), GO:0023057 (negative regulation of signaling), GO:0051051 (negative regulation of transport), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0035176 (social behavior), GO:0050794 (regulation of cellular process), GO:0023051 (regulation of signaling), GO:0048523 (negative regulation of cellular process), GO:0007610 (behavior), GO:0046888 (negative regulation of hormone secretion), GO:0010648 (negative regulation of cell communication), GO:1903530 (regulation of secretion by cell), GO:0051049 (regulation of transport), GO:0046883 (regulation of hormone secretion), GO:0009410 (response to xenobiotic stimulus), GO:0010646 (regulation of cell communication), GO:1903828 (negative regulation of protein localization), GO:0060341 (regulation of cellular localization), GO:0051224 (negative regulation of protein transport), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0010817 (regulation of hormone levels), GO:0051048 (negative regulation of secretion), GO:1903531 (negative regulation of secretion by cell), GO:0051223 (regulation of protein transport), GO:0090276 (regulation of peptide hormone secretion), GO:0090087 (regulation of peptide transport), GO:0051246 (regulation of protein metabolic process), GO:0070201 (regulation of establishment of protein localization), GO:0002792 (negative regulation of peptide secretion), GO:0050709 (negative regulation of protein secretion), GO:0051046 (regulation of secretion), GO:0032880 (regulation of protein localization), GO:0050708 (regulation of protein secretion), GO:1904950 (negative regulation of establishment of protein localization), GO:0090278 (negative regulation of peptide hormone secretion), GO:0051174 (regulation of phosphorus metabolic process), GO:0046676 (negative regulation of insulin secretion), GO:0002791 (regulation of peptide secretion), GO:0031399 (regulation of protein modification process), GO:0050796 (regulation of insulin secretion), GO:0019220 (regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0001932 (regulation of protein phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure)