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Details on Person UniProt:Q6R327 RICTOR

Class:Id	ReferenceGeneProduct:245693
_chainChangeLog	chain:1-1708 added on Fri February 6 2015
_displayName	UniProt:Q6R327 RICTOR
_timestamp	2025-02-21 18:51:01
chain	chain:1-1708
checksum	DB7B1E4A45DAE2AB
comment	FUNCTION Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718).SUBUNIT Component of the mechanistic target of rapamycin complex 2 (mTORC2), consisting in two heterotretramers composed of MTOR, MLST8, RICTOR and MAPKAP1/SIN1 (PubMed:15268862, PubMed:15467718, PubMed:17461779, PubMed:17599906, PubMed:29424687, PubMed:29567957, PubMed:33158864, PubMed:34519268, PubMed:35926713). The mTORC2 core complex associates with PRR5/PROTOR1 and/or PRR5L/PROTOR2 (PubMed:17461779, PubMed:21964062, PubMed:29424687). Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin (PubMed:15467718, PubMed:33158864). Binds directly to MTOR and PRR5 within the TORC2 complex; interaction with MTOR is enhanced by deubiquitination of RICTOR by USP9X (PubMed:15268862, PubMed:17461779, PubMed:17599906, PubMed:33378666). Interaction with MAPKAP1 is not enhanced by RICTOR deubiquitination by USP9X (PubMed:33378666). Interacts with CCDC28B (PubMed:23727834). Interacts with NBN (PubMed:23762398). Interacts with SIK3 (PubMed:30232230). Interacts with NCKAP1L (PubMed:32647003). Interacts with kinases GSK3A and GSK3B; the interactions lead to phosphorylation of RICTOR at Thr-1695 which facilitates its FBXW7-mediated ubiquitination and subsequent degradation (PubMed:25897075). Interacts with FBXW7; the interaction is enhanced by GSK3-mediated phosphorylation of Thr-1695 and results in RICTOR ubiquitination and degradation (PubMed:25897075). Interacts with ARMH4 (via cytoplasmic tail); this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity (By similarity). Interacts with UBXN2A (PubMed:37037900). Interacts with TSPAN8 (PubMed:25761241, PubMed:35904232).SUBUNIT (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates MTOR.INTERACTION The mTORC2 complex localizes to membranes: mTORC2 is active at the plasma membrane, endoplasmic reticulum membrane and lysosomes (PubMed:21867682). Iin lysosomal membrane, mTORC2 is sensitive to lysosomal positioning in the cell (PubMed:31130364).ALTERNATIVE PRODUCTS Phosphorylated by MTOR; when part of mTORC2 (PubMed:15467718). Phosphorylated at Thr-1135 by RPS6KB1 downstream of the mTORC1 complex: phosphorylation of RICTOR inhibits mTORC2 signaling by creating a binding site for 14-3-3 proteins (PubMed:19720745, PubMed:19935711, PubMed:19995915). Phosphorylated at Thr-1695 by GSK3A and GSK3B which facilitates RICTOR ubiquitination and subsequent degradation (PubMed:25897075). Phosphorylated at Ser-1235 by GSK3B in response to endoplasmic stress, inhibiting mTORC2 signaling (PubMed:21343617).PTM Ubiquitinated by the SCF(FBXW7) complex, leading to its degradation by the proteasome (PubMed:25897075). Deubiquitinated by USP9X; deubiquitination stabilizes RICTOR and enhances its binding to MTOR, thus promoting mTORC2 complex assembly (PubMed:33378666).PTM Acetylated by EP300/p300 in response to glucose, leading to activate the mTORC2 complex (PubMed:22084251, PubMed:26170313). Acetylation by BLOC1S1/GCN5L1 in response to hypotoxic stress protects RICTOR against ubiquitination and subsequent degradation by the proteasome (PubMed:38281616).MISCELLANEOUS May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.SIMILARITY Belongs to the RICTOR family.SEQUENCE CAUTION Wrong choice of CDS.
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
description	recommendedName: fullName evidence="40"Rapamycin-insensitive companion of mTOR alternativeName: fullName evidence="37"AVO3 homolog shortName: hAVO3
geneName	RICTOR KIAA1999
identifier	Q6R327
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing ATP-binding Cell membrane Developmental protein Endoplasmic reticulum Host-virus interaction Isopeptide bond Lysosome Membrane Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Ubl conjugation Zinc
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 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
name	RICTOR
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9004365] ENSEMBL:ENSG00000164327 RICTOR [Homo sapiens]
secondaryIdentifier	RICTR_HUMAN B2RNX0 B7ZMF7 Q68DT5 Q86UB7 Q8N3A0 Q8NCM6
sequenceLength	1708
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:245695] UniProt:Q6R327-3 RICTOR [Homo sapiens] [ReferenceIsoform:408635] UniProt:Q6R327-1 RICTOR [Homo sapiens] [ReferenceIsoform:8969842] UniProt:Q6R327-4 RICTOR [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:198632] RICTOR [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q6R327 RICTOR (245693)