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Details on Person UniProt:Q8N122-1 RPTOR
| Class:Id | ReferenceIsoform:153287 |
|---|---|
| _chainChangeLog | chain:1-1335 added on Sat February 7 2015 |
| _displayName | UniProt:Q8N122-1 RPTOR |
| _timestamp | 2024-11-03 20:07:27 |
| chain | chain:1-1335 |
| checksum | 688ED1943F45045A |
| comment | 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).SUBUNIT Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:12408816, PubMed:24403073, PubMed:25940091, PubMed:27909983, PubMed:29236692, PubMed:31601708, PubMed:31601764, PubMed:36697823). mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity (PubMed:17386266, PubMed:31601764). mTORC1 associates with DEPTOR, which regulates its activity (PubMed:34519268, PubMed:34519269). mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:12408816, PubMed:15066126). Forms a complex with MTOR under both leucine-rich and -poor conditions (PubMed:12408816, PubMed:25940091, PubMed:31601708, PubMed:31601764). Interacts with (via TOS motifs) EIF4EBP1 and RPS6KB1; interaction is independent of its association with MTOR (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073). Binds preferentially to poorly or non-phosphorylated forms of EIF4EBP1, and this binding is critical to the ability of MTOR to catalyze phosphorylation (PubMed:12747827, PubMed:24403073). Interacts with ULK1 in a nutrient-dependent manner; the interaction is reduced during starvation (PubMed:19211835). Interacts with GTP-bound form of RagA/RRAGA or RagB/RRAGB and GDP-bound form of RagC/RRAGC or RagD/RRAGD, promoting recruitment of mTORC1 to the lysosomes (PubMed:31601708, PubMed:31601764). Interacts (when phosphorylated by AMPK) with 14-3-3 protein, leading to inhibition of its activity (PubMed:18439900). Interacts with SPAG5; SPAG5 competes with MTOR for RPTOR-binding, resulting in decreased mTORC1 formation (PubMed:23953116). Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). Interacts with G3BP1 (PubMed:23953116). The complex formed with G3BP1 and SPAG5 is increased by oxidative stress (PubMed:23953116). Interacts with HTR6 (PubMed:23027611). Interacts with PIH1D1 (PubMed:24036451). Interacts with LARP1 (PubMed:25940091). Interacts with BRAT1 (PubMed:25657994). Interacts with SIK3 (PubMed:30232230). Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation (PubMed:35561222).SUBUNIT (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates mTOR.INTERACTION 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).ALTERNATIVE PRODUCTS Highly expressed in skeletal muscle, and in a lesser extent in brain, lung, small intestine, kidney and placenta.TISSUE SPECIFICITY Widely expressed, with highest levels in nasal mucosa and pituitary and lowest in spleen.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).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).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).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).SIMILARITY Belongs to the WD repeat RAPTOR family. |
| created | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 |
| description | recommendedName: fullName evidence="46"Regulatory-associated protein of mTOR shortName evidence="42 43"Raptor alternativeName: fullName evidence="43"p150 target of rapamycin (TOR)-scaffold protein |
| geneName | RPTOR KIAA1303 RAPTOR |
| identifier | Q8N122 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Cytoplasm Glycoprotein Host-virus interaction Isopeptide bond Lysosome Membrane Phosphoprotein Proteomics identification Reference proteome Repeat Ubl conjugation WD repeat |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | RPTOR |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8994478] ENSEMBL:ENSG00000141564 RPTOR [Homo sapiens] |
| secondaryIdentifier | RPTOR_HUMAN B2RN36 C6KEF2 F5H7J5 Q8N4V9 Q8TB32 Q9P2P3 |
| sequenceLength | 1335 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q8N122-1 |
| (referenceEntity) | [EntityWithAccessionedSequence:447067] p-S722,S792-RPTOR-1 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:447064] O-phospho-L-serine at 722 [ModifiedResidue:447065] O-phospho-L-serine at 792 |
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No pathways have been reviewed or authored by UniProt:Q8N122-1 RPTOR (153287)
