Regulatory-associated protein of mTOR

UniProt Q8N122 Organism Homo sapiens Gene KIAA1303, RAPTOR, RPTOR

Also known as: KIAA1303, RAPTOR, RPTOR

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. 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). 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. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. 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. 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).

Classification

Family (Pfam): PF02985 HEAT, PF14538 Raptor_N, PF00400 WD40
InterPro: ARM-like, ARM-type_fold, HEAT, Raptor, Raptor_N, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf, WD40_rpt
Functional cluster: Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 22

5H64 EM 4.40A
6BCU EM 3.43A
6BCX EM 3.00A
6SB0 EM 5.50A
6SB2 EM 6.20A
6U62 EM 3.18A
7OWG EM 4.70A
7PEA EM 4.07A
7PEB EM 3.67A
7PEC EM 4.24A
7UX2 EM 2.90A
7UXC EM 3.20A
… and 10 more

A predicted model is available from AlphaFold.

Gene Ontology · 43

Drugs targeting this protein · 1

INDOXIMOD activator

Related proteins · sequence + function similarity

Regulatory-associated protein of mTOR 1.00
Dystrobrevin alpha 0.83
AP-2 complex subunit alpha-2 0.82
AP-2 complex subunit alpha-2 0.82
Dystrobrevin alpha 0.81
AP-2 complex subunit alpha-2 0.81
Ral GTPase-activating protein subunit beta 0.81
26S proteasome non-ATPase regulatory subunit 1 0.81
Metastasis-associated protein MTA1 0.81
AP-2 complex subunit alpha-2 0.80
26S proteasome non-ATPase regulatory subunit 1 0.80
Alpha-globin transcription factor CP2 0.80

Co-cited proteins · studied together in the literature

Regulatory-associated protein of mTOR 5 shared papers
Serine/threonine-protein kinase mTOR 19 shared papers
Target of rapamycin complex subunit LST8 10 shared papers
Eukaryotic translation initiation factor 4E-binding protein 1 4 shared papers
PIH1 domain-containing protein 1 1 shared papers
ADP-ribosylation factor 5 1 shared papers
Phosphoprotein OPG062 1 shared papers
Proline-rich AKT1 substrate 1 3 shared papers
Sodium-coupled neutral amino acid transporter 7 1 shared papers
von Hippel-Lindau disease tumor suppressor 1 shared papers
La-related protein 1 1 shared papers
DEP domain-containing mTOR-interacting protein 3 shared papers

Literature · 55 cited papers

O-GlcNAcylation of Raptor transduces glucose signals to mTORC1. Mol. Cell · 2023
Arf5-mediated regulation of mTORC1 at the plasma membrane. Mol. Biol. Cell · 2023
Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex. Nature · 2023
Phosphorylation of OTUB1 at Tyr 26 stabilizes the mTORC1 component, Raptor. Cell Death Differ. · 2023
SNAT7 regulates mTORC1 via macropinocytosis. Proc. Natl. Acad. Sci. U.S.A. · 2022
Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace. Elife · 2021
Regulation of human mTOR complexes by DEPTOR. Elife · 2021
VHL suppresses RAPTOR and inhibits mTORC1 signaling in clear cell renal cell carcinoma. Sci. Rep. · 2021
Leucine regulates autophagy via acetylation of the mTORC1 component raptor. Nat. Commun. · 2020
Architecture of human Rag GTPase heterodimers and their complex with mTORC1. Science · 2019
Structural basis for the docking of mTORC1 on the lysosomal surface. Science · 2019
TBK1 limits mTORC1 by promoting phosphorylation of Raptor Ser877. Sci. Rep. · 2019
… and 43 more in the literature graph

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