Q8K4Q0
uniprot
Q8K4Q0
canonical
amino_acid_sequence
MESEMLQSPLMGLGEEDEADLTDWNLPLAFMKKRHCEKIEGSKSLAQSWRMKDRMKTVSVALVLCLNVGVDPPDVVKTTPCARLECWIDPLSMGPQKALETIGANLQKQYENWQPRARYKQSLDPTVDEVKKLCTSLRRNAKEERVLFHYNGHGVPRPTVNGEVWVFNKNYTQYIPLSIYDLQTWMGSPSIFVYDCSNAGLIVKSFKQFALQREQELEVAAINPNHPLAQMPLPPSMKNCIQLAACEAHELLPMIPDLPADLFTSCLTTPIKIALRWFCMQKCVSLVPGVTLDLIEKIPGRLNDRRTPLGELNWIFTAITDTIAWNVLPRDLFQKLFRQDLLVASLFRNFLLAERIMRSYNCTPVSSPRLPPTYMHAMWQAWDLAVDICLSQLPTIIEEGTAFRHSPFFAEQLTAFQVWLTMGVENRSPPEQLPIVLQVLLSQVHRLRALDLLGRFLDLGPWAVSLALSVGIFPYVLKLLQSSARELRPLLVFIWAKILAVDSSCQADLVKDNGHKYFLSVLADPYMPAEHRTMTAFILAVIVNSYTTGQEACLQGNLIAICLEQLSDPHPLLRQWVAICLGRIWQNFDSARWCGVRDSAHEKLYSLLSDPIPEVRCAAVFALGTFVGNSAERTDHSTTIDHNVAMMLAQLINDGSPMVRKELVVALSHLVVQYESNFCTVALQFMEEEKNYPLPSPAATEGGSLTPVRDSPCTPRLRSVSSYGNIRAVTTARNLNKSLQNLSLTEESGSSVAFSPGNLSTSSSASSTLGSPENEEYILSFETIDKMRRVSSYSALNSLIGVSFNSVYTQIWRVLLHLAADPYPDVSDLAMKVLNSIAYKATVNARPQRILDTSSLTQSAPASPTNKGMHMHQVGGSPPASSTSSCSLTNDVAKQTVSRDLPSSRPGTAGPTGAQYTPHSHQFPRTRKMFDKGPDQTTDDADDAAGHKSFICASMQTGFCDWSARYFAQAVMKIPEEHDLESQIRKEREWRFLRNTRVRKQAQQVIQKGITRLDDQIFLNRNPGVPSVVKFHPFTPCIAVADKDSICFWDWEKGEKLDYFHNGNPRYTRVTAMEYLNGQDCSLLLTATDDGAIRVWKNFADLEKNPEMVTAWQGLSDMLPTTRGAGMVVDWEQETGLLMSSGDVRIVRIWDTDRETKVQDIPTGADSCVTSLSCDSHRSLIVAGLGDGSIRVYDRRMALSECRVMTYREHTAWVVKAYLQKHPEGHIVSVSVNGDVRFFDPRMPESVNVMQIVKGLTALDIHPQANLIACGSMNQFTAIYNGNGELINNIKYYDGFMGQRVGAISCLAFHPHWPHLAVGSNDYYISVYSVEKRVR
uniprot
proteins
function
FUNCTION: Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:27879318, PubMed:32912901). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (PubMed:27879318). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy (By similarity). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (By similarity). Within the mTORC1 complex, RPTOR acts both as a molecular adapter, which (1) mediates recruitment of mTORC1 to lysosomal membranes via interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), and a (2) substrate-specific adapter, which promotes substrate specificity by binding to TOS motif-containing proteins and direct them towards the active site of the MTOR kinase domain for phosphorylation (By similarity). mTORC1 complex regulates many cellular processes, such as odontoblast and osteoclast differentiation or neuronal transmission (PubMed:27879318, PubMed:30984011, PubMed:33495318). mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD) (PubMed:33495318). {ECO:0000250|UniProtKB:Q8N122, ECO:0000269|PubMed:27879318, ECO:0000269|PubMed:30984011, ECO:0000269|PubMed:32912901, ECO:0000269|PubMed:33495318}.
uniprot
proteins
mass_dalton
149471
uniprot
proteins
mutagenesis
MUTAGEN 722; /note="S->A: Abolishes AMPK-mediated phosphorylation; when associated with A-792. In Raptor(AA) mutant; knockin mice display higher mTORC1 activity; when associated with A-792."; /evidence="ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:32912901"; MUTAGEN 792; /note="S->A: Abolishes AMPK-mediated phosphorylation; when associated with A-722. In Raptor(AA) mutant; knockin mice display higher mTORC1 activity; when associated with A-722."; /evidence="ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:32912901"; MUTAGEN 863; /note="S->A: Abolished phosphorylation by NLK, leading to impaired inhibition of the mTORC1 complex in response to osmotic stress."; /evidence="ECO:0000269|PubMed:26588989
uniprot
proteins
post_translational_modification
PTM: Insulin-stimulated phosphorylation at Ser-863 by MTOR and MAPK8 regulates mTORC1 activity (PubMed:19346248). Phosphorylated at Ser-863 by NLK in response to stress, disrupting the interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), thereby preventing lysosome recruitment and activation of the mTORC1 complex (PubMed:26588989). Osmotic stress also induces phosphorylation at Ser-696, Thr-706 and Ser-863 by MAPK8 (By similarity). Ser-863 phosphorylation is required for phosphorylation at Ser-855 and Ser-859 (By similarity). In response to nutrient limitation, phosphorylated at Ser-722 and Ser-792 by AMPK; phosphorylation promotes interaction with 14-3-3 proteins, leading to negative regulation of the mTORC1 complex (PubMed:18439900, PubMed:32912901). Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation by OGT and subsequent activation of mTORC1 (By similarity). In response to growth factors, phosphorylated at Ser-719, Ser-721 and Ser-722 by RPS6KA1, which stimulates mTORC1 activity (By similarity). Phosphorylation at Ser-791 by PKA downstream of cAMP inhibits the mTORC1 complex (Probable) (PubMed:31112131). Phosphorylated at Ser-877 by TBK1, leading to negative regulation of the mTORC1 complex (By similarity). {ECO:0000250|UniProtKB:Q8N122, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:19346248, ECO:0000269|PubMed:26588989, ECO:0000269|PubMed:32912901, ECO:0000305|PubMed:31112131}.; PTM: O-GlcNAcylated by OGT upon glucose sufficiency, promoting interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) and subsequent recruitment of mTORC1 to lysosomal membranes, leading to activation of the mTORC1 complex (By similarity). Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation (By similarity). {ECO:0000250|UniProtKB:Q8N122}.; PTM: Acetylation at Lys-1097 by EP300/p300 in response to leucine metabolite acetyl-coA promotes its activity, leading to activation of the mTORC1 complex (By similarity). Acetylation is decreased in response to fasting (PubMed:30197302). Phosphorylated at Ser-877 by TBK1, leading to negative regulation of the mTORC1 complex (By similarity). {ECO:0000250|UniProtKB:Q8N122, ECO:0000269|PubMed:30197302}.; PTM: Ubiquitinated, leading to its degradation by the proteasome (By similarity). Deubiquitinated by OTUB1 via a non-catalytic mechanism (By similarity). Ubiquitinated by an E3 ubiquitin ligase complex containing VHL (By similarity). {ECO:0000250|UniProtKB:Q8N122}.
uniprot
proteins
protein_family
WD repeat RAPTOR family
uniprot
proteins
pubmed
12150926
uniprot
proteins
pubmed
15345747
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17141160
uniprot
proteins
pubmed
18439900
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19346248
uniprot
proteins
pubmed
20801936
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
26588989
uniprot
proteins
pubmed
27879318
uniprot
proteins
pubmed
30197302
uniprot
proteins
pubmed
30984011
uniprot
proteins
pubmed
31112131
uniprot
proteins
pubmed
32912901
uniprot
proteins
pubmed
33495318
uniprot
proteins
sequence_length
1335
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8N122}. Lysosome {ECO:0000250|UniProtKB:Q8N122}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q8N122}. Note=Targeting to lysosomes depends on amino acid availability: recruited to lysosomes via interaction with GTP-bound form of RRAGA (or RRAGB) in complex with the GDP-bound form of RRAGC (or RRAGD), promoting recruitment of mTORC1 to the lysosomes. In arsenite-stressed cells, accumulates in stress granules when associated with SPAG5 and association with lysosomes is drastically decreased. {ECO:0000250|UniProtKB:Q8N122}.
uniprot
proteins