RRAGA
entrez
10670
canonical
uniprot
Q7L523
canonical
ensembl
ENSG00000155876
resolver
ensp
ENSP00000369899
resolver
enst
ENST00000380527
resolver
genesymbol
RRAGA
resolver
hgnc
HGNC:16963
resolver
uniprot
B2R7L1
resolver
uniprot
O00290
resolver
uniprot
Q15347
resolver
uniprot_entry
RRAGA_HUMAN
resolver
uniprot_sec
B2R7L1
resolver
uniprot_sec
O00290
resolver
uniprot_sec
Q15347
resolver
activity_regulation
ACTIVITY REGULATION: The activation of GTP-binding proteins is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (PubMed:22980980, PubMed:23723238). The Ragulator complex functions as a GEF and promotes the active GTP-bound form (PubMed:22980980). The GATOR1 complex functions as a GAP and stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound form, preventing mTORC1 recruitment and activation (PubMed:23723238, PubMed:29590090). {ECO:0000269|PubMed:22980980, ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:29590090}.
uniprot
proteins
amino_acid_sequence
MPNTAMKKKVLLMGKSGSGKTSMRSIIFANYIARDTRRLGATIDVEHSHVRFLGNLVLNLWDCGGQDTFMENYFTSQRDNIFRNVEVLIYVFDVESRELEKDMHYYQSCLEAILQNSPDAKIFCLVHKMDLVQEDQRDLIFKEREEDLRRLSRPLECACFRTSIWDETLYKAWSSIVYQLIPNVQQLEMNLRNFAQIIEADEVLLFERATFLVISHYQCKEQRDVHRFEKISNIIKQFKLSCSKLAASFQSMEVRNSNFAAFIDIFTSNTYVMVVMSDPSIPSAATLINIRNARKHFEKLERVDGPKHSLLMR
uniprot
proteins
ec_number
3.6.5.-
uniprot
proteins
function
FUNCTION: Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:25936802, PubMed:31601708, PubMed:31601764, PubMed:38103557). Forms heterodimeric Rag complexes with RagC/RRAGC or RagD/RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form: RagA/RRAGA is in its active form when GTP-bound RagA/RRAGA forms a complex with GDP-bound RagC/RRAGC (or RagD/RRAGD) and in an inactive form when GDP-bound RagA/RRAGA heterodimerizes with GTP-bound RagC/RRAGC (or RagD/RRAGD) (PubMed:20381137, PubMed:24095279, PubMed:25936802, PubMed:31601708, PubMed:31601764, PubMed:32868926). In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:25936802, PubMed:31601708, PubMed:31601764). Involved in the RCC1/Ran-GTPase pathway (PubMed:9394008). May play a direct role in a TNF signaling pathway leading to induction of cell death (PubMed:8995684). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:25936802, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31601764, ECO:0000269|PubMed:32868926, ECO:0000269|PubMed:38103557, ECO:0000269|PubMed:8995684, ECO:0000269|PubMed:9394008}.; FUNCTION: (Microbial infection) May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF functions, thereby affecting cell death. {ECO:0000269|PubMed:8995684}.
uniprot
proteins
mass_dalton
36566
uniprot
proteins
mutagenesis
MUTAGEN 21; /note="T->N: Reduced affinity for all nucleotides, but with preferential binding of GDP over GTP."; /evidence="ECO:0000269|PubMed:24095279, ECO:0000269|PubMed:31704029"; MUTAGEN 29; /note="A->F: In RA3 mutant; abolished interaction with RPTOR without affecting GTP-binding; when associated with Y-35 and A-46."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 31; /note="Y->A: In RA1 mutant; abolished interaction with RPTOR without affecting GTP-binding. Does not affect interaction with TFE3 and TFEB."; /evidence="ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:36608670"; MUTAGEN 35; /note="D->A: In RA2 mutant; abolished interaction with RPTOR without affecting GTP-binding; when associated with A-46. Does not affect interaction with TFE3 and TFEB; when associated with A-46."; /evidence="ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:36608670"; MUTAGEN 35; /note="D->Y: In RA3 mutant; abolished interaction with RPTOR without affecting GTP-binding; when associated with F-29 and A-46."; /evidence="ECO:0000269|PubMed:31601708"; MUTAGEN 46; /note="E->A: In RA2 mutant; abolished interaction with RPTOR without affecting GTP-binding; when associated with A-35. In RA3 mutant; abolished interaction with RPTOR without affecting GTP-binding; when associated with F-29 and Y-35. Abolished interaction with RPTOR without affecting interaction with TFE3 and TFEB. Does not affect interaction with TFE3 and TFEB; when associated with A-35."; /evidence="ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:36608670"; MUTAGEN 66; /note="Q->L: Maintains GTP-bound state, leading to activate mTORC1."; /evidence="ECO:0000269|PubMed:31601764"; MUTAGEN 71; /note="E->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 100; /note="E->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 104; /note="H->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 107; /note="Q->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 111; /note="E->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 142; /note="K->R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-220, R-230 and R-244."; /evidence="ECO:0000269|PubMed:25936802"; MUTAGEN 151; /note="L->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 153; /note="R->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 154; /note="P->A: Abolished interaction with TFE3 and TFEB without affecting interaction with RPTOR."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 220; /note="K->R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-142, R-230 and R-244."; /evidence="ECO:0000269|PubMed:25936802"; MUTAGEN 230; /note="K->R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-244."; /evidence="ECO:0000269|PubMed:25936802"; MUTAGEN 244; /note="K->R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-230."; /evidence="ECO:0000269|PubMed:25936802
uniprot
proteins
post_translational_modification
PTM: Polybiquitinated via 'Lys-63'-linked polyubiquitination by RNF152 in response to amino acid starvation: polyubiquitination of the GDP-bound inactive form by RNF152 promotes RRAGA inactivation and interaction with the GATOR1 complex (PubMed:25936802). This does not affect RRAGA degradation (PubMed:25936802). {ECO:0000269|PubMed:25936802}.
uniprot
proteins
protein_family
GTR/RAG GTP-binding protein family
uniprot
proteins
pubmed
11073942
uniprot
proteins
pubmed
14660641
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18497260
uniprot
proteins
pubmed
20381137
uniprot
proteins
pubmed
22575674
uniprot
proteins
pubmed
22980980
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23723238
uniprot
proteins
pubmed
24095279
uniprot
proteins
pubmed
25259925
uniprot
proteins
pubmed
25561175
uniprot
proteins
pubmed
25567906
uniprot
proteins
pubmed
25936802
uniprot
proteins
pubmed
28935770
uniprot
proteins
pubmed
29158492
uniprot
proteins
pubmed
29590090
uniprot
proteins
pubmed
31036939
uniprot
proteins
pubmed
31601708
uniprot
proteins
pubmed
31601764
uniprot
proteins
pubmed
31672913
uniprot
proteins
pubmed
31704029
uniprot
proteins
pubmed
32868926
uniprot
proteins
pubmed
35338845
uniprot
proteins
pubmed
36103527
uniprot
proteins
pubmed
36608670
uniprot
proteins
pubmed
36697823
uniprot
proteins
pubmed
38103557
uniprot
proteins
pubmed
7499430
uniprot
proteins
pubmed
8995684
uniprot
proteins
pubmed
9394008
uniprot
proteins
sequence_length
313
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:8995684, ECO:0000269|PubMed:9394008}. Nucleus {ECO:0000269|PubMed:8995684, ECO:0000269|PubMed:9394008}. Lysosome membrane {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:31036939}. Note=Predominantly cytoplasmic (PubMed:8995684, PubMed:9394008). Recruited to the lysosome surface by the Ragulator complex (PubMed:20381137, PubMed:28935770, PubMed:29158492). May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state (PubMed:8995684, PubMed:9394008). Colocalizes in vivo with adenovirus E3-14.7K mainly to the cytoplasm especially near the nuclear membrane and in discrete foci on or near the plasma membrane (PubMed:8995684). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:28935770, ECO:0000269|PubMed:29158492, ECO:0000269|PubMed:8995684, ECO:0000269|PubMed:9394008}.
uniprot
proteins