RPTOR
entrez
57521
canonical
uniprot
Q8N122
canonical
ensembl
ENSG00000141564
resolver
ensp
ENSP00000307272
resolver
ensp
ENSP00000442479
resolver
genesymbol
RPTOR
resolver
genesymbol_syn
KIAA1303
resolver
genesymbol_syn
RAPTOR
resolver
hgnc
HGNC:30287
resolver
uniprot
B2RN36
resolver
uniprot
C6KEF2
resolver
uniprot
F5H7J5
resolver
uniprot
Q8N4V9
resolver
uniprot
Q8TB32
resolver
uniprot
Q9P2P3
resolver
uniprot_entry
RPTOR_HUMAN
resolver
uniprot_sec
B2RN36
resolver
uniprot_sec
C6KEF2
resolver
uniprot_sec
F5H7J5
resolver
uniprot_sec
Q8N4V9
resolver
uniprot_sec
Q8TB32
resolver
uniprot_sec
Q9P2P3
resolver
amino_acid_sequence
MESEMLQSPLLGLGEEDEADLTDWNLPLAFMKKRHCEKIEGSKSLAQSWRMKDRMKTVSVALVLCLNVGVDPPDVVKTTPCARLECWIDPLSMGPQKALETIGANLQKQYENWQPRARYKQSLDPTVDEVKKLCTSLRRNAKEERVLFHYNGHGVPRPTVNGEVWVFNKNYTQYIPLSIYDLQTWMGSPSIFVYDCSNAGLIVKSFKQFALQREQELEVAAINPNHPLAQMPLPPSMKNCIQLAACEATELLPMIPDLPADLFTSCLTTPIKIALRWFCMQKCVSLVPGVTLDLIEKIPGRLNDRRTPLGELNWIFTAITDTIAWNVLPRDLFQKLFRQDLLVASLFRNFLLAERIMRSYNCTPVSSPRLPPTYMHAMWQAWDLAVDICLSQLPTIIEEGTAFRHSPFFAEQLTAFQVWLTMGVENRNPPEQLPIVLQVLLSQVHRLRALDLLGRFLDLGPWAVSLALSVGIFPYVLKLLQSSARELRPLLVFIWAKILAVDSSCQADLVKDNGHKYFLSVLADPYMPAEHRTMTAFILAVIVNSYHTGQEACLQGNLIAICLEQLNDPHPLLRQWVAICLGRIWQNFDSARWCGVRDSAHEKLYSLLSDPIPEVRCAAVFALGTFVGNSAERTDHSTTIDHNVAMMLAQLVSDGSPMVRKELVVALSHLVVQYESNFCTVALQFIEEEKNYALPSPATTEGGSLTPVRDSPCTPRLRSVSSYGNIRAVATARSLNKSLQNLSLTEESGGAVAFSPGNLSTSSSASSTLGSPENEEHILSFETIDKMRRASSYSSLNSLIGVSFNSVYTQIWRVLLHLAADPYPEVSDVAMKVLNSIAYKATVNARPQRVLDTSSLTQSAPASPTNKGVHIHQAGGSPPASSTSSSSLTNDVAKQPVSRDLPSGRPGTTGPAGAQYTPHSHQFPRTRKMFDKGPEQTADDADDAAGHKSFISATVQTGFCDWSARYFAQPVMKIPEEHDLESQIRKEREWRFLRNSRVRRQAQQVIQKGITRLDDQIFLNRNPGVPSVVKFHPFTPCIAVADKDSICFWDWEKGEKLDYFHNGNPRYTRVTAMEYLNGQDCSLLLTATDDGAIRVWKNFADLEKNPEMVTAWQGLSDMLPTTRGAGMVVDWEQETGLLMSSGDVRIVRIWDTDREMKVQDIPTGADSCVTSLSCDSHRSLIVAGLGDGSIRVYDRRMALSECRVMTYREHTAWVVKASLQKRPDGHIVSVSVNGDVRIFDPRMPESVNVLQIVKGLTALDIHPQADLIACGSVNQFTAIYNSSGELINNIKYYDGFMGQRVGAISCLAFHPHWPHLAVGSNDYYISVYSVEKRVR
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:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:26588989, PubMed:32561715, PubMed:37541260). 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:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:26588989, PubMed:37541260). 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 (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:32561715, PubMed:37541260). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:37541260). 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 (PubMed:12747827, PubMed:24403073, PubMed:26588989, PubMed:37541260). mTORC1 complex regulates many cellular processes, such as odontoblast and osteoclast differentiation or neuronal transmission (By similarity). mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD) (By similarity). {ECO:0000250|UniProtKB:Q8K4Q0, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:26588989, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:37541260}.
uniprot
proteins
mass_dalton
149038
uniprot
proteins
mutagenesis
MUTAGEN 557..564; /note="NLIAICLE->ALIFICLA: In alpha24 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 560; /note="A->F: In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with E-597 and A-635."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 594..598; /note="CGVRD->AGVYA: In alpha26 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 597; /note="R->E: In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with F-560 and A-635."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 634..636; /note="TDH->ARE: In alpha29 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 635; /note="D->A: In alphax3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes; when associated with F-560 and E-597."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 699; /note="T->A: Does not affect O-GlcNAcylation in response to glucose sufficiency."; /evidence="ECO:0000269|PubMed:37541260"; MUTAGEN 700; /note="T->A: Abolished O-GlcNAcylation in response to glucose sufficiency, leading to decreased mTORC1 activation."; /evidence="ECO:0000269|PubMed:37541260"; MUTAGEN 722; /note="S->A: Abolishes AMPK-mediated phosphorylation; when associated with A-792. Increased O-GlcNAcylation; when associated with A-792."; /evidence="ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:37541260"; MUTAGEN 737; /note="K->R: Does not affect ubiquitination."; /evidence="ECO:0000269|PubMed:35927303"; MUTAGEN 791; /note="S->A,D: Abolished phosphorylation after forskolin treatment."; /evidence="ECO:0000269|PubMed:31112131"; MUTAGEN 792; /note="S->A: Abolishes AMPK-mediated phosphorylation; when associated with A-722. Increased O-GlcNAcylation; when associated with A-722. Does not affect phosphorylation after forskolin treatment."; /evidence="ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:37541260"; 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"; MUTAGEN 863; /note="S->D: Mimics phosphorylation, leading to impaired interaction with small GTPases Rag and activation of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:26588989"; MUTAGEN 877; /note="S->A: Decreased phosphorylation, leading to increased activity of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31530866"; MUTAGEN 894; /note="K->R: Does not affect ubiquitination."; /evidence="ECO:0000269|PubMed:35927303"; MUTAGEN 916..936; /note="Missing: In Clw1 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 919..921; /note="HSH->AAA: In Clw2 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 925..928; /note="RTRK->ATAA: In Clw3 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 932; /note="K->R: Decreased ubiquitination."; /evidence="ECO:0000269|PubMed:35927303"; MUTAGEN 933..935; /note="GPE->RGR: In Clw4 mutant; abolished interaction with GTP-bound RRAGA and recruitment to lysosomes without affecting the composition of the mTORC1 complex."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 948; /note="K->R: Decreased ubiquitination."; /evidence="ECO:0000269|PubMed:35927303"; MUTAGEN 1097; /note="K->R: Reduced acetylation, leading to decreased activation of the mTORC complex."; /evidence="ECO:0000269|PubMed:30197302
uniprot
proteins
post_translational_modification
PTM: Insulin-stimulated phosphorylation at Ser-863 by MTOR and MAPK8 regulates mTORC1 activity (PubMed:19864431). 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 (PubMed:19864431, PubMed:22493283). Ser-863 phosphorylation is required for phosphorylation at Ser-855 and Ser-859 (PubMed:19864431). 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). Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation by OGT and subsequent activation of mTORC1 (PubMed:37541260). In response to growth factors, phosphorylated at Ser-719, Ser-721 and Ser-722 by RPS6KA1, which stimulates mTORC1 activity (PubMed:18439900, PubMed:18722121). Phosphorylation at Ser-791 by PKA downstream of cAMP inhibits the mTORC1 complex (PubMed:31112131). Phosphorylated at Ser-877 by TBK1, leading to negative regulation of the mTORC1 complex (PubMed:31530866). {ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:19864431, ECO:0000269|PubMed:22493283, ECO:0000269|PubMed:26588989, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:37541260}.; 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 (PubMed:37541260). Phosphorylation at Ser-722 and Ser-792 by AMPK in response to glucose starvation inhibits O-GlcNAcylation (PubMed:37541260). {ECO:0000269|PubMed:37541260}.; 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 (PubMed:30197302, PubMed:32561715). Acetylation is decreased in response to fasting (By similarity). {ECO:0000250|UniProtKB:Q8K4Q0, ECO:0000269|PubMed:30197302, ECO:0000269|PubMed:32561715}.; PTM: Ubiquitinated, leading to its degradation by the proteasome (PubMed:34290272, PubMed:35927303). Deubiquitinated by OTUB1 via a non-catalytic mechanism (PubMed:35927303). Ubiquitinated by an E3 ubiquitin ligase complex containing VHL (PubMed:34290272). {ECO:0000269|PubMed:34290272, ECO:0000269|PubMed:35927303}.
uniprot
proteins
protein_family
WD repeat RAPTOR family
uniprot
proteins
pubmed
10718198
uniprot
proteins
pubmed
12150925
uniprot
proteins
pubmed
12150926
uniprot
proteins
pubmed
12408816
uniprot
proteins
pubmed
12747827
uniprot
proteins
pubmed
15066126
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17386266
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18439900
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18722121
uniprot
proteins
pubmed
19211835
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19388141
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19864431
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20381137
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22493283
uniprot
proteins
pubmed
23027611
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23953116
uniprot
proteins
pubmed
24036451
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24403073
uniprot
proteins
pubmed
25657994
uniprot
proteins
pubmed
25940091
uniprot
proteins
pubmed
26588989
uniprot
proteins
pubmed
26812014
uniprot
proteins
pubmed
27909983
uniprot
proteins
pubmed
29236692
uniprot
proteins
pubmed
30078703
uniprot
proteins
pubmed
30197302
uniprot
proteins
pubmed
30232230
uniprot
proteins
pubmed
31112131
uniprot
proteins
pubmed
31530866
uniprot
proteins
pubmed
31601708
uniprot
proteins
pubmed
31601764
uniprot
proteins
pubmed
32561715
uniprot
proteins
pubmed
34290272
uniprot
proteins
pubmed
34519268
uniprot
proteins
pubmed
34519269
uniprot
proteins
pubmed
35561222
uniprot
proteins
pubmed
35927303
uniprot
proteins
pubmed
36697823
uniprot
proteins
pubmed
36735494
uniprot
proteins
pubmed
37541260
uniprot
proteins
sequence_length
1335
uniprot
proteins
subcellular_location
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}.
uniprot
proteins