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Protein

Ras-related GTP-binding protein A

Gene

RRAGA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.4 Publications

Enzyme regulationi

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:25936802). The GATOR1 complex functions as a GAP and stimulates RRAGA GTPase activity to turn it into its inactive GDP-bound form (PubMed:25936802, PubMed:23723238).1 Publication1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi14 – 21GTPBy similarity8
Nucleotide bindingi62 – 66GTPBy similarity5
Nucleotide bindingi127 – 130GTPBy similarity4

GO - Molecular functioni

  • GTPase activity Source: SGD
  • GTP binding Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle arrest Source: Reactome
  • cell death Source: UniProtKB
  • cellular protein localization Source: UniProtKB
  • cellular response to amino acid starvation Source: UniProtKB
  • cellular response to amino acid stimulus Source: UniProtKB
  • macroautophagy Source: Reactome
  • modulation by virus of host morphology or physiology Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • positive regulation of cytolysis Source: UniProtKB
  • positive regulation of TORC1 signaling Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Host-virus interaction

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155876-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SIGNORiQ7L523.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-related GTP-binding protein ACurated
Short name:
Rag A1 Publication
Short name:
RagA1 Publication
Alternative name(s):
Adenovirus E3 14.7 kDa-interacting protein 11 Publication
FIP-11 Publication
Gene namesi
Name:RRAGAImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:16963. RRAGA.

Subcellular locationi

  • Cytoplasm 2 Publications
  • Nucleus 2 Publications
  • Lysosome 1 Publication

  • Note: Predominantly cytoplasmic. 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).3 Publications

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • EGO complex Source: GO_Central
  • Golgi apparatus Source: HPA
  • Gtr1-Gtr2 GTPase complex Source: GO_Central
  • intracellular membrane-bounded organelle Source: HPA
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lysosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi142K → R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-220, R-230 and R-244. 1 Publication1
Mutagenesisi220K → R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with R-142, R-230 and R-244. 1 Publication1
Mutagenesisi230K → R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-244. 1 Publication1
Mutagenesisi244K → R: Prevents RRAGA ubiquitination and alters interaction and regulation by GATOR1; when associated with RR-142, R-220 and R-230. 1 Publication1

Organism-specific databases

DisGeNETi10670.
OpenTargetsiENSG00000155876.
PharmGKBiPA134980509.

Polymorphism and mutation databases

BioMutaiRRAGA.
DMDMi74759007.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002399451 – 313Ras-related GTP-binding protein AAdd BLAST313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki220Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki230Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei309PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated. 'Lys-68'-linked polyubiquitination of the GDP-bound inactive form of RRAGA by RNF152 is increased in response to amino acid starvation. Polyubiquitination promotes interaction with the GATOR1 complex. This does not affect RRAGA degradation.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ7L523.
MaxQBiQ7L523.
PaxDbiQ7L523.
PeptideAtlasiQ7L523.
PRIDEiQ7L523.

PTM databases

iPTMnetiQ7L523.
PhosphoSitePlusiQ7L523.

Expressioni

Tissue specificityi

Ubiquitously expressed with highest levels of expression in skeletal muscle, heart, and brain.1 Publication

Gene expression databases

BgeeiENSG00000155876.
CleanExiHS_RRAGA.
GenevisibleiQ7L523. HS.

Organism-specific databases

HPAiHPA003734.

Interactioni

Subunit structurei

Can occur as a homodimer or as a heterodimer with RRAGC or RRAGD in a sequence-independent manner; heterodimerization stabilizes proteins of the heterodimer (PubMed:11073942, PubMed:20381137). In complex with RRAGC, but not with RRAGB, interacts with RPTOR (PubMed:18497260). The GTP-bound form of RRAGA interacts with NOL8 (PubMed:14660641). 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 (PubMed:22575674). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts (inactive GDP-bound form) with RNF152; stimulated by amino acid starvation (PubMed:25936802). Interacts (polyubiquitinated) with the GATOR1 complex; inactivates RRAGA (PubMed:25936802). Interacts (polyubiquitinated) with TSC2 (PubMed:25936802). Interacts with adenovirus E3 14.7 kDa protein (PubMed:8995684). Interacts with SESN1, SESN2 AND SESN3 (PubMed:25259925).11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LAMTOR1Q6IAA810EBI-752376,EBI-715385
RRAGCQ9HB9018EBI-752376,EBI-752390
RRAGDQ9NQL28EBI-752376,EBI-992949
SLC38A9Q8NBW411EBI-752376,EBI-9978316

GO - Molecular functioni

  • phosphoprotein binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115912. 20 interactors.
DIPiDIP-37516N.
IntActiQ7L523. 11 interactors.
MINTiMINT-155844.
STRINGi9606.ENSP00000369899.

Structurei

3D structure databases

ProteinModelPortaliQ7L523.
SMRiQ7L523.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the GTR/RAG GTP-binding protein family.Curated

Phylogenomic databases

eggNOGiKOG3886. Eukaryota.
ENOG410XQ0R. LUCA.
GeneTreeiENSGT00550000074769.
HOGENOMiHOG000173258.
HOVERGENiHBG052715.
InParanoidiQ7L523.
KOiK16185.
OMAiVHYYQSC.
OrthoDBiEOG091G050Q.
PhylomeDBiQ7L523.
TreeFamiTF300616.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR006762. Gtr1_RagA.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11259. PTHR11259. 1 hit.
PfamiPF04670. Gtr1_RagA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.

Sequencei

Sequence statusi: Complete.

Q7L523-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPNTAMKKKV LLMGKSGSGK TSMRSIIFAN YIARDTRRLG ATIDVEHSHV
60 70 80 90 100
RFLGNLVLNL WDCGGQDTFM ENYFTSQRDN IFRNVEVLIY VFDVESRELE
110 120 130 140 150
KDMHYYQSCL EAILQNSPDA KIFCLVHKMD LVQEDQRDLI FKEREEDLRR
160 170 180 190 200
LSRPLECACF RTSIWDETLY KAWSSIVYQL IPNVQQLEMN LRNFAQIIEA
210 220 230 240 250
DEVLLFERAT FLVISHYQCK EQRDVHRFEK ISNIIKQFKL SCSKLAASFQ
260 270 280 290 300
SMEVRNSNFA AFIDIFTSNT YVMVVMSDPS IPSAATLINI RNARKHFEKL
310
ERVDGPKHSL LMR
Length:313
Mass (Da):36,566
Last modified:July 5, 2004 - v1
Checksum:iB0DA1FC8FA6B766A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti229E → G in AAB63255 (PubMed:8995684).Curated1
Sequence conflicti246A → P in AAB63255 (PubMed:8995684).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X90529 mRNA. Translation: CAA62131.1.
U41654 mRNA. Translation: AAB63255.1.
AL356000 Genomic DNA. Translation: CAH72136.1.
AK313023 mRNA. Translation: BAG35858.1.
CH471071 Genomic DNA. Translation: EAW58653.1.
BC006433 mRNA. Translation: AAH06433.1.
BC009990 mRNA. Translation: AAH09990.1.
CCDSiCCDS6488.1.
PIRiI38176.
RefSeqiNP_006561.1. NM_006570.4.
UniGeneiHs.743260.

Genome annotation databases

EnsembliENST00000380527; ENSP00000369899; ENSG00000155876.
GeneIDi10670.
KEGGihsa:10670.
UCSCiuc003znj.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X90529 mRNA. Translation: CAA62131.1.
U41654 mRNA. Translation: AAB63255.1.
AL356000 Genomic DNA. Translation: CAH72136.1.
AK313023 mRNA. Translation: BAG35858.1.
CH471071 Genomic DNA. Translation: EAW58653.1.
BC006433 mRNA. Translation: AAH06433.1.
BC009990 mRNA. Translation: AAH09990.1.
CCDSiCCDS6488.1.
PIRiI38176.
RefSeqiNP_006561.1. NM_006570.4.
UniGeneiHs.743260.

3D structure databases

ProteinModelPortaliQ7L523.
SMRiQ7L523.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115912. 20 interactors.
DIPiDIP-37516N.
IntActiQ7L523. 11 interactors.
MINTiMINT-155844.
STRINGi9606.ENSP00000369899.

PTM databases

iPTMnetiQ7L523.
PhosphoSitePlusiQ7L523.

Polymorphism and mutation databases

BioMutaiRRAGA.
DMDMi74759007.

Proteomic databases

EPDiQ7L523.
MaxQBiQ7L523.
PaxDbiQ7L523.
PeptideAtlasiQ7L523.
PRIDEiQ7L523.

Protocols and materials databases

DNASUi10670.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380527; ENSP00000369899; ENSG00000155876.
GeneIDi10670.
KEGGihsa:10670.
UCSCiuc003znj.4. human.

Organism-specific databases

CTDi10670.
DisGeNETi10670.
GeneCardsiRRAGA.
HGNCiHGNC:16963. RRAGA.
HPAiHPA003734.
MIMi612194. gene.
neXtProtiNX_Q7L523.
OpenTargetsiENSG00000155876.
PharmGKBiPA134980509.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3886. Eukaryota.
ENOG410XQ0R. LUCA.
GeneTreeiENSGT00550000074769.
HOGENOMiHOG000173258.
HOVERGENiHBG052715.
InParanoidiQ7L523.
KOiK16185.
OMAiVHYYQSC.
OrthoDBiEOG091G050Q.
PhylomeDBiQ7L523.
TreeFamiTF300616.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155876-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
SIGNORiQ7L523.

Miscellaneous databases

ChiTaRSiRRAGA. human.
GeneWikiiRRAGA.
GenomeRNAii10670.
PROiQ7L523.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155876.
CleanExiHS_RRAGA.
GenevisibleiQ7L523. HS.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR006762. Gtr1_RagA.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR11259. PTHR11259. 1 hit.
PfamiPF04670. Gtr1_RagA. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRRAGA_HUMAN
AccessioniPrimary (citable) accession number: Q7L523
Secondary accession number(s): B2R7L1, O00290, Q15347
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.