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Protein

Ras-related GTP-binding protein A

Gene

RRAGA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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: CAFA
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processApoptosis, Host-virus interaction
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

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
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8943724 Regulation of PTEN gene transcription
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

EuPathDBiHostDB:ENSG00000155876.5
HGNCiHGNC:16963 RRAGA
MIMi612194 gene
neXtProtiNX_Q7L523

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi68791

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 Expressed in 233 organ(s), highest expression level in central nervous system
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 SESN1, SESN2 AND SESN3 (PubMed:25259925).10 Publications
(Microbial infection) Interacts with adenovirus E3 14.7 kDa protein.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115912, 22 interactors
DIPiDIP-37516N
IntActiQ7L523, 13 interactors
STRINGi9606.ENSP00000369899

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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
OMAiIRINIRM
OrthoDBiEOG091G050Q
PhylomeDBiQ7L523
TreeFamiTF300616

Family and domain databases

CDDicd11384 RagA_like, 1 hit
InterProiView protein in InterPro
IPR006762 Gtr1_RagA
IPR027417 P-loop_NTPase
IPR039397 RagA/B
PANTHERiPTHR11259 PTHR11259, 2 hits
PfamiView protein in Pfam
PF04670 Gtr1_RagA, 1 hit
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 No translation available.
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

Similar proteinsi

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 No translation available.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5X6VX-ray2.02F183-313[»]
6CESelectron microscopy4.00A1-313[»]
6EHRX-ray2.90F183-313[»]
ProteinModelPortaliQ7L523
SMRiQ7L523
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115912, 22 interactors
DIPiDIP-37516N
IntActiQ7L523, 13 interactors
STRINGi9606.ENSP00000369899

PTM databases

iPTMnetiQ7L523
PhosphoSitePlusiQ7L523

Polymorphism and mutation databases

BioMutaiRRAGA
DMDMi74759007

Proteomic databases

EPDiQ7L523
MaxQBiQ7L523
PaxDbiQ7L523
PeptideAtlasiQ7L523
PRIDEiQ7L523
ProteomicsDBi68791

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
EuPathDBiHostDB:ENSG00000155876.5
GeneCardsiRRAGA
HGNCiHGNC:16963 RRAGA
HPAiHPA003734
MIMi612194 gene
neXtProtiNX_Q7L523
OpenTargetsiENSG00000155876
PharmGKBiPA134980509
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-8943724 Regulation of PTEN gene transcription
SIGNORiQ7L523

Miscellaneous databases

ChiTaRSiRRAGA human
GeneWikiiRRAGA
GenomeRNAii10670
PROiPR:Q7L523
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155876 Expressed in 233 organ(s), highest expression level in central nervous system
CleanExiHS_RRAGA
GenevisibleiQ7L523 HS

Family and domain databases

CDDicd11384 RagA_like, 1 hit
InterProiView protein in InterPro
IPR006762 Gtr1_RagA
IPR027417 P-loop_NTPase
IPR039397 RagA/B
PANTHERiPTHR11259 PTHR11259, 2 hits
PfamiView protein in Pfam
PF04670 Gtr1_RagA, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRRAGA_HUMAN
AccessioniPrimary (citable) accession number: Q7L523
Secondary accession number(s): B2R7L1, O00290, Q15347
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 143 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

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