Q80X95 · RRAGA_MOUSE
- ProteinRas-related GTP-binding protein A
- GeneRraga
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids313 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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:23263183).
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:23263183).
In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:23263183).
Involved in the RCC1/Ran-GTPase pathway (By similarity).
May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death (By similarity).
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:23263183).
In its GTP-bound active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:23263183).
Involved in the RCC1/Ran-GTPase pathway (By similarity).
May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death (By similarity).
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
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) (By similarity).
The Ragulator complex functions as a GEF and promotes the active GTP-bound form (By similarity).
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 (By similarity).
The Ragulator complex functions as a GEF and promotes the active GTP-bound form (By similarity).
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 (By similarity).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 16 | GTP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 17 | GDP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 17 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 19 | GDP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 19 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 20 | GDP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 20 | GTP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 21 | GDP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 21 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 22 | GDP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 22 | GTP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 36 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 42 | GTP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 65 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 127 | GDP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 127 | GTP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 130 | GDP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 148 | GDP (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 164 | GDP (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 164 | GTP (UniProtKB | ChEBI) | ||||
Sequence: I |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-related GTP-binding protein A
- EC number
- Short namesRag A ; RagA
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ80X95
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly cytoplasmic. Recruited to the lysosome surface by the Ragulator complex. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 66 | Maintains GTP-bound state, leading to activate mTORC1. Knockin mice develop normally, but die within 1 day postpartum because of constitutive activation of mTORC1 that prevents response to fasting. Inhibition of mTORC1 is required for neonatal autophagy and thus nutrient homeostasis. | ||||
Sequence: Q → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 9 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, cross-link, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000239946 | 1-313 | Ras-related GTP-binding protein A | |||
Sequence: MPNTAMKKKVLLMGKSGSGKTSMRSIIFANYIARDTRRLGATIDVEHSHVRFLGNLVLNLWDCGGQDTFMENYFTSQRDNIFRNVEVLIYVFDVESRELEKDMHYYQSCLEAILQNSPDAKIFCLVHKMDLVQEDQRDLIFKEREEDLRRLSRPLECACFRTSIWDETLYKAWSSIVYQLIPNVQQLEMNLRNFAQIIEADEVLLFERATFLVISHYQCKEQRDVHRFEKISNIIKQFKLSCSKLAASFQSMEVRNSNFAAFIDIFTSNTYVMVVMSDPSIPSAATLINIRNARKHFEKLERVDGPKHSLLMR | ||||||
Cross-link | 142 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 220 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 230 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Cross-link | 244 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 309 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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. This does not affect RRAGA degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Can occur as a homodimer or as a heterodimer with RRAGC or RRAGD in a sequence-independent manner; heterodimerization stabilizes proteins of the heterodimer (By similarity).
The GTP-bound form of RRAGA (in complex with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity).
The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (By similarity).
The Rag heterodimer interacts with the Ragulator complex (By similarity).
The GTP-bound form of RRAGA interacts with NOL8 (By similarity).
Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity).
Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGA and is negatively regulated by amino acids (By similarity).
Interacts (polyubiquitinated) with TSC2 (By similarity).
Interacts with SESN1, SESN2 and SESN3 (By similarity).
Interacts with PIP4P1 (PubMed:29644770).
Interacts with GPR137B (By similarity).
Interacts with WDR83; this interaction regulates the spatiotemporal localization of mTORC1 to the lysosomal surface (By similarity).
The GTP-bound form of RRAGA (in complex with the GDP-bound form of RRAGC or RRAGD) interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (By similarity).
The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (By similarity).
The Rag heterodimer interacts with the Ragulator complex (By similarity).
The GTP-bound form of RRAGA interacts with NOL8 (By similarity).
Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity).
Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGA and is negatively regulated by amino acids (By similarity).
Interacts (polyubiquitinated) with TSC2 (By similarity).
Interacts with SESN1, SESN2 and SESN3 (By similarity).
Interacts with PIP4P1 (PubMed:29644770).
Interacts with GPR137B (By similarity).
Interacts with WDR83; this interaction regulates the spatiotemporal localization of mTORC1 to the lysosomal surface (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length313
- Mass (Da)36,566
- Last updated2003-06-01 v1
- ChecksumB0DA1FC8FA6B766A
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK004955 EMBL· GenBank· DDBJ | BAC25103.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AK144591 EMBL· GenBank· DDBJ | BAE25953.1 EMBL· GenBank· DDBJ | mRNA | ||
AL824707 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC037615 EMBL· GenBank· DDBJ | AAH37615.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC048245 EMBL· GenBank· DDBJ | AAH48245.1 EMBL· GenBank· DDBJ | mRNA |