UniProtKB - Q9NQL2 (RRAGD_HUMAN)
Ras-related GTP-binding protein D
RRAGD
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 (PubMed:20381137, PubMed:24095279).
Forms heterodimeric Rag complexes with RRAGA or RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form (PubMed:24095279).
In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279).
This is a crucial step in the activation of the TOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279).
2 PublicationsCatalytic activityi
- This reaction proceeds in the forward1 Publication direction.
Activity regulationi
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 69 – 77 | GTP1 Publication | 9 | |
Nucleotide bindingi | 117 – 121 | GTP1 Publication | 5 | |
Nucleotide bindingi | 179 – 182 | GTP1 Publication | 4 |
GO - Molecular functioni
- GDP binding Source: CAFA
- GTPase activity Source: CAFA
- GTPase binding Source: CAFA
- GTP binding Source: CAFA
- protein heterodimerization activity Source: UniProtKB
GO - Biological processi
- cellular protein localization Source: UniProtKB
- cellular response to amino acid stimulus Source: UniProtKB
- cellular response to leucine Source: CAFA
- cellular response to leucine starvation Source: CAFA
- cellular response to starvation Source: GO_Central
- positive regulation of TORC1 signaling Source: CAFA
- positive regulation of TOR signaling Source: GO_Central
- regulation of autophagy Source: GO_Central
Keywordsi
Molecular function | Hydrolase |
Ligand | GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9NQL2 |
Reactomei | R-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-8943724, Regulation of PTEN gene transcription R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q9NQL2 |
SIGNORi | Q9NQL2 |
Names & Taxonomyi
Protein namesi | Recommended name: Ras-related GTP-binding protein D (EC:3.6.5.-1 Publication)Short name: Rag D Short name: RagD |
Gene namesi | Name:RRAGDImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:19903, RRAGD |
MIMi | 608268, gene |
neXtProti | NX_Q9NQL2 |
VEuPathDBi | HostDB:ENSG00000025039 |
Subcellular locationi
Cytoskeleton
- centrosome Source: HPA
Cytosol
- cytosol Source: Reactome
Lysosome
- lysosome Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: HGNC-UCL
Other locations
- cytoplasm Source: HGNC-UCL
- Gtr1-Gtr2 GTPase complex Source: GO_Central
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
Cytoplasm, Lysosome, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 76 | S → L: Increased RPTOR-binding. 1 Publication | 1 | |
Mutagenesisi | 121 | Q → L: Decreased RPTOR-binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 58528 |
OpenTargetsi | ENSG00000025039 |
PharmGKBi | PA134957148 |
Miscellaneous databases
Pharosi | Q9NQL2, Tbio |
Genetic variation databases
BioMutai | RRAGD |
DMDMi | 74752904 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000239953 | 1 – 400 | Ras-related GTP-binding protein DAdd BLAST | 400 |
Proteomic databases
EPDi | Q9NQL2 |
jPOSTi | Q9NQL2 |
MassIVEi | Q9NQL2 |
MaxQBi | Q9NQL2 |
PaxDbi | Q9NQL2 |
PeptideAtlasi | Q9NQL2 |
PRIDEi | Q9NQL2 |
ProteomicsDBi | 82161 [Q9NQL2-1] 82162 [Q9NQL2-2] |
PTM databases
GlyGeni | Q9NQL2, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9NQL2 |
PhosphoSitePlusi | Q9NQL2 |
Expressioni
Gene expression databases
Bgeei | ENSG00000025039, Expressed in saliva-secreting gland and 253 other tissues |
Genevisiblei | Q9NQL2, HS |
Organism-specific databases
HPAi | ENSG00000025039, Tissue enhanced (skeletal) |
Interactioni
Subunit structurei
Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization stabilizes RRAG proteins (PubMed:11073942, PubMed:14660641, PubMed:25561175, PubMed:25567906). In complex with RRAGB, interacts with RPTOR; this interaction is particularly efficient with GTP-loaded RRAGB and GDP-loaded RRAGC (PubMed:18497260).
Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (By similarity).
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 RRAGD 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 with SESN1, SESN2 and SESN3 (PubMed:25259925).
By similarity7 PublicationsBinary interactionsi
Q9NQL2
With | #Exp. | IntAct |
---|---|---|
LARS1 [Q9P2J5] | 13 | EBI-992949,EBI-356077 |
RRAGA [Q7L523] | 9 | EBI-992949,EBI-752376 |
RRAGB [Q5VZM2] | 7 | EBI-992949,EBI-993049 |
GO - Molecular functioni
- GTPase binding Source: CAFA
- protein heterodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121848, 25 interactors |
IntActi | Q9NQL2, 11 interactors |
STRINGi | 9606.ENSP00000358423 |
Miscellaneous databases
RNActi | Q9NQL2, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9NQL2 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9NQL2 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 54 | DisorderedSequence analysisAdd BLAST | 54 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 12 – 29 | Acidic residuesSequence analysisAdd BLAST | 18 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3887, Eukaryota |
GeneTreei | ENSGT00950000183031 |
HOGENOMi | CLU_047421_1_1_1 |
InParanoidi | Q9NQL2 |
OMAi | EYNVVFF |
OrthoDBi | 1216811at2759 |
PhylomeDBi | Q9NQL2 |
TreeFami | TF300659 |
Family and domain databases
CDDi | cd11385, RagC_like, 1 hit |
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR006762, Gtr1_RagA IPR027417, P-loop_NTPase IPR039400, RagC/D |
PANTHERi | PTHR11259, PTHR11259, 1 hit |
Pfami | View protein in Pfam PF04670, Gtr1_RagA, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSQVLGKPQP QDEDDAEEEE EEDELVGLAD YGDGPDSSDA DPDSGTEEGV
60 70 80 90 100
LDFSDPFSTE VKPRILLMGL RRSGKSSIQK VVFHKMSPNE TLFLESTNKI
110 120 130 140 150
CREDVSNSSF VNFQIWDFPG QIDFFDPTFD YEMIFRGTGA LIFVIDSQDD
160 170 180 190 200
YMEALARLHL TVTRAYKVNT DINFEVFIHK VDGLSDDHKI ETQRDIHQRA
210 220 230 240 250
NDDLADAGLE KIHLSFYLTS IYDHSIFEAF SKVVQKLIPQ LPTLENLLNI
260 270 280 290 300
FISNSGIEKA FLFDVVSKIY IATDSTPVDM QTYELCCDMI DVVIDISCIY
310 320 330 340 350
GLKEDGAGTP YDKESTAIIK LNNTTVLYLK EVTKFLALVC FVREESFERK
360 370 380 390 400
GLIDYNFHCF RKAIHEVFEV RMKVVKSRKV QNRLQKKKRA TPNGTPRVLL
Sequence cautioni
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052078 | 1 – 151 | Missing in isoform 2. 1 PublicationAdd BLAST | 151 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF272036 mRNA Translation: AAG32663.1 AK289799 mRNA Translation: BAF82488.1 AL138717 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48554.1 AL137502 mRNA Translation: CAB70775.2 BC003088 mRNA Translation: AAH03088.1 Different initiation. |
CCDSi | CCDS5022.1 [Q9NQL2-1] |
PIRi | T46254 |
RefSeqi | NP_067067.1, NM_021244.4 [Q9NQL2-1] |
Genome annotation databases
Ensembli | ENST00000359203; ENSP00000352131; ENSG00000025039 [Q9NQL2-2] ENST00000369415; ENSP00000358423; ENSG00000025039 |
GeneIDi | 58528 |
KEGGi | hsa:58528 |
MANE-Selecti | ENST00000369415.9; ENSP00000358423.4; NM_021244.5; NP_067067.1 |
UCSCi | uc003pnd.5, human [Q9NQL2-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF272036 mRNA Translation: AAG32663.1 AK289799 mRNA Translation: BAF82488.1 AL138717 Genomic DNA No translation available. CH471051 Genomic DNA Translation: EAW48554.1 AL137502 mRNA Translation: CAB70775.2 BC003088 mRNA Translation: AAH03088.1 Different initiation. |
CCDSi | CCDS5022.1 [Q9NQL2-1] |
PIRi | T46254 |
RefSeqi | NP_067067.1, NM_021244.4 [Q9NQL2-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2Q3F | X-ray | 2.10 | A/B | 60-239 | [»] | |
SMRi | Q9NQL2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121848, 25 interactors |
IntActi | Q9NQL2, 11 interactors |
STRINGi | 9606.ENSP00000358423 |
PTM databases
GlyGeni | Q9NQL2, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9NQL2 |
PhosphoSitePlusi | Q9NQL2 |
Genetic variation databases
BioMutai | RRAGD |
DMDMi | 74752904 |
Proteomic databases
EPDi | Q9NQL2 |
jPOSTi | Q9NQL2 |
MassIVEi | Q9NQL2 |
MaxQBi | Q9NQL2 |
PaxDbi | Q9NQL2 |
PeptideAtlasi | Q9NQL2 |
PRIDEi | Q9NQL2 |
ProteomicsDBi | 82161 [Q9NQL2-1] 82162 [Q9NQL2-2] |
Protocols and materials databases
Antibodypediai | 31866, 130 antibodies from 26 providers |
DNASUi | 58528 |
Genome annotation databases
Ensembli | ENST00000359203; ENSP00000352131; ENSG00000025039 [Q9NQL2-2] ENST00000369415; ENSP00000358423; ENSG00000025039 |
GeneIDi | 58528 |
KEGGi | hsa:58528 |
MANE-Selecti | ENST00000369415.9; ENSP00000358423.4; NM_021244.5; NP_067067.1 |
UCSCi | uc003pnd.5, human [Q9NQL2-1] |
Organism-specific databases
CTDi | 58528 |
DisGeNETi | 58528 |
GeneCardsi | RRAGD |
HGNCi | HGNC:19903, RRAGD |
HPAi | ENSG00000025039, Tissue enhanced (skeletal) |
MIMi | 608268, gene |
neXtProti | NX_Q9NQL2 |
OpenTargetsi | ENSG00000025039 |
PharmGKBi | PA134957148 |
VEuPathDBi | HostDB:ENSG00000025039 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3887, Eukaryota |
GeneTreei | ENSGT00950000183031 |
HOGENOMi | CLU_047421_1_1_1 |
InParanoidi | Q9NQL2 |
OMAi | EYNVVFF |
OrthoDBi | 1216811at2759 |
PhylomeDBi | Q9NQL2 |
TreeFami | TF300659 |
Enzyme and pathway databases
PathwayCommonsi | Q9NQL2 |
Reactomei | R-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-8943724, Regulation of PTEN gene transcription R-HSA-9639288, Amino acids regulate mTORC1 |
SignaLinki | Q9NQL2 |
SIGNORi | Q9NQL2 |
Miscellaneous databases
BioGRID-ORCSi | 58528, 20 hits in 1041 CRISPR screens |
ChiTaRSi | RRAGD, human |
EvolutionaryTracei | Q9NQL2 |
GenomeRNAii | 58528 |
Pharosi | Q9NQL2, Tbio |
PROi | PR:Q9NQL2 |
RNActi | Q9NQL2, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000025039, Expressed in saliva-secreting gland and 253 other tissues |
Genevisiblei | Q9NQL2, HS |
Family and domain databases
CDDi | cd11385, RagC_like, 1 hit |
Gene3Di | 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR006762, Gtr1_RagA IPR027417, P-loop_NTPase IPR039400, RagC/D |
PANTHERi | PTHR11259, PTHR11259, 1 hit |
Pfami | View protein in Pfam PF04670, Gtr1_RagA, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RRAGD_HUMAN | |
Accessioni | Q9NQL2Primary (citable) accession number: Q9NQL2 Secondary accession number(s): A8K184, Q7L8F9, Q9NPG0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 13, 2006 |
Last sequence update: | October 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 147 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families