Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Electronic Gene Ontology annotations created by ARBA machine learning models
Integral and associated lysosomal membrane proteins.
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
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Human HEK293T co-IP separates DEPDC5/NPRL2/NPRL3 GATOR1 from GATOR2; tagged DEPDC5 associates with RagA/C and localizes to the lysosomal surface. DEPDC5 depletion prevents amino-acid-dependent mTORC1 shutoff. Purified GATOR1 accelerates RagA/B GTP hydrolysis, without GDP-release stimulation in the tested assay. These experiments establish complex-level GAP activity, not autonomous DEPDC5 catalysis. Fly perturbations are distinguished from human-cell data.
The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1.
Sestrins inhibit mTORC1 kinase activation through the GATOR complex.
KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1.
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Endogenous-level FLAG-DEPDC5 identifies KICSTOR. Endogenous complex co-IP, imaging of tagged GATOR1 components and purified lysosomes show that KICSTOR recruits GATOR1 to lysosomes. KICSTOR loss disperses GATOR1 and weakens Rag/GATOR2 association. Several localization assays use NPRL2 as the GATOR1 marker rather than imaging DEPDC5 directly; whole-complex inference and the independent2013 DEPDC5 localization support the location. Amino-acid-insensitive recruitment does not imply inactive GATOR1 in all conditions.
Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.
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Human GATOR1 structures and biochemical assays identify DEPDC5 interfaces for NPRL2 and RagA. DEPDC5 alone has no measured GAP activity; NPRL2/NPRL3 performs it at higher concentrations. Mutating the RagA-contacting critical strip increases GAP kinetics, showing that this binding state restrains the catalytic module. DEPDC5 assembly mutants fail to restore amino-acid regulation in knockout cells. Engineered 1–720 truncations and point mutants are not natural short isoforms.
KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.
A reference map of the human binary protein interactome.
Cryo-EM structures of the human GATOR1-Rag-Ragulator complex reveal a spatial-constraint regulated GAP mechanism.
SESN1,2 binds L-leucine and dissociates from GATOR2
CASTOR1 in CASTOR1:CASTOR2 binds L-arginine and dissociates from GATOR2
BMT2 (SAMTOR) binds S-adenosylmethionine and dissociates from KICSTOR:GATOR1
CASTOR1 homodimer binds L-arginine and dissociates from GATOR2
Mutations in DEPDC5 cause familial focal epilepsy with variable foci.
Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation.
Reply to: Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation.
Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3 inactivates TORC1 and induces autophagy.
Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase.
Amino acid deprivation inhibits TORC1 through a GTPase-activating protein complex for the Rag family GTPase Gtr1.
Selective regulation of autophagy by the Iml1-Npr2-Npr3 complex in the absence of nitrogen starvation.
Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases.
Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells.
SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway.