Aliases for RRAGA Gene

Aliases for RRAGA Gene

  • Ras Related GTP Binding A 2 3 5
  • FIP-1 2 3 4
  • Adenovirus E3 14.7 KDa-Interacting Protein 1 3 4
  • Ras-Related GTP-Binding Protein A 3 4
  • Rag A 3 4
  • RAGA 2 3
  • Adenovirus E3-14.7K Interacting Protein 1 3
  • Ras-Related GTP Binding A 2
  • EC 3.6.5.- 4
  • RRAGA 5
  • FIP1 3
  • RagA 4

External Ids for RRAGA Gene

Previous GeneCards Identifiers for RRAGA Gene

  • GC09P019039
  • GC09P019010

Summaries for RRAGA Gene

GeneCards Summary for RRAGA Gene

RRAGA (Ras Related GTP Binding A) is a Protein Coding gene. Diseases associated with RRAGA include Birt-Hogg-Dube Syndrome and Cone-Rod Dystrophy 2. Among its related pathways are Macroautophagy and TP53 Regulates Metabolic Genes. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and GTP binding. An important paralog of this gene is RRAGB.

UniProtKB/Swiss-Prot Summary for RRAGA Gene

  • 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). Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form (PubMed:20381137, PubMed:24095279, PubMed:25936802). In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:25936802). Involved in the RCC1/Ran-GTPase pathway (PubMed:9394008). May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death (PubMed:8995684).
  • (Microbial infection) May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.

Gene Wiki entry for RRAGA Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RRAGA Gene

Genomics for RRAGA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RRAGA Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RRAGA on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RRAGA

Top Transcription factor binding sites by QIAGEN in the RRAGA gene promoter:
  • AML1a
  • Arnt
  • Brachyury
  • CUTL1
  • IRF-7A
  • Pax-4a
  • RORalpha1
  • STAT1
  • TFIID
  • Zic3

Genomic Locations for RRAGA Gene

Latest Assembly
chr9:19,049,427-19,051,025
(GRCh38/hg38)
Size:
1,599 bases
Orientation:
Plus strand

Previous Assembly
chr9:19,049,425-19,051,023
(GRCh37/hg19 by Entrez Gene)
Size:
1,599 bases
Orientation:
Plus strand

chr9:19,049,372-19,051,019
(GRCh37/hg19 by Ensembl)
Size:
1,648 bases
Orientation:
Plus strand

Genomic View for RRAGA Gene

Genes around RRAGA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RRAGA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RRAGA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RRAGA Gene

Proteins for RRAGA Gene

  • Protein details for RRAGA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q7L523-RRAGA_HUMAN
    Recommended name:
    Ras-related GTP-binding protein A
    Protein Accession:
    Q7L523
    Secondary Accessions:
    • B2R7L1
    • O00290
    • Q15347

    Protein attributes for RRAGA Gene

    Size:
    313 amino acids
    Molecular mass:
    36566 Da
    Quaternary structure:
    • 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). 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 (PubMed:31704029, PubMed:31672913). 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). Interacts with PIP4P1 (By similarity). Interacts with GPR137B (PubMed:31036939).
    • (Microbial infection) Interacts with adenovirus E3 14.7 kDa protein.

    Three dimensional structures from OCA and Proteopedia for RRAGA Gene

neXtProt entry for RRAGA Gene

Post-translational modifications for RRAGA Gene

  • 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.
  • Ubiquitination at Lys142, Lys220, Lys230, and Lys244
  • Modification sites at PhosphoSitePlus

Other Protein References for RRAGA Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for RRAGA Gene

Domains & Families for RRAGA Gene

Gene Families for RRAGA Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for RRAGA Gene

Suggested Antigen Peptide Sequences for RRAGA Gene

GenScript: Design optimal peptide antigens:
  • FIP-1 (RRAGA_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q7L523

UniProtKB/Swiss-Prot:

RRAGA_HUMAN :
  • Belongs to the GTR/RAG GTP-binding protein family.
Family:
  • Belongs to the GTR/RAG GTP-binding protein family.
genes like me logo Genes that share domains with RRAGA: view

Function for RRAGA Gene

Molecular function for RRAGA Gene

UniProtKB/Swiss-Prot 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). Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form (PubMed:20381137, PubMed:24095279, PubMed:25936802). In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:25936802). Involved in the RCC1/Ran-GTPase pathway (PubMed:9394008). May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death (PubMed:8995684).
UniProtKB/Swiss-Prot Function:
(Microbial infection) May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000305|PubMed:24095279};.
UniProtKB/Swiss-Prot EnzymeRegulation:
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).

Enzyme Numbers (IUBMB) for RRAGA Gene

Phenotypes From GWAS Catalog for RRAGA Gene

Gene Ontology (GO) - Molecular Function for RRAGA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003924 GTPase activity IDA 23723238
GO:0005515 protein binding IPI 8995684
GO:0005525 GTP binding IDA 7499430
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with RRAGA: view
genes like me logo Genes that share phenotypes with RRAGA: view

Animal Models for RRAGA Gene

MGI Knock Outs for RRAGA:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RRAGA

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RRAGA Gene

Localization for RRAGA Gene

Subcellular locations from UniProtKB/Swiss-Prot for RRAGA Gene

Cytoplasm. Nucleus. Lysosome. 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). {ECO:0000269 PubMed:20381137, ECO:0000269 PubMed:8995684, ECO:0000269 PubMed:9394008}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RRAGA gene
Compartment Confidence
nucleus 5
lysosome 5
endosome 4
cytosol 4
mitochondrion 3
golgi apparatus 3
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RRAGA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 8995684
GO:0005737 cytoplasm IEA,IDA 9394008
GO:0005764 lysosome IBA,IDA 20381137
GO:0005765 lysosomal membrane HDA 17897319
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with RRAGA: view

Pathways & Interactions for RRAGA Gene

genes like me logo Genes that share pathways with RRAGA: view

Pathways by source for RRAGA Gene

Gene Ontology (GO) - Biological Process for RRAGA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006915 apoptotic process IEA --
GO:0007050 cell cycle arrest TAS --
GO:0008219 cell death TAS,IDA 8995684
GO:0009267 cellular response to starvation IBA 21873635
GO:0010506 regulation of autophagy IBA 21873635
genes like me logo Genes that share ontologies with RRAGA: view

No data available for SIGNOR curated interactions for RRAGA Gene

Drugs & Compounds for RRAGA Gene

(3) Drugs for RRAGA Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0
genes like me logo Genes that share compounds with RRAGA: view

Transcripts for RRAGA Gene

mRNA/cDNA for RRAGA Gene

1 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RRAGA

Alternative Splicing Database (ASD) splice patterns (SP) for RRAGA Gene

No ASD Table

Relevant External Links for RRAGA Gene

GeneLoc Exon Structure for
RRAGA

Expression for RRAGA Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RRAGA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RRAGA Gene

This gene is overexpressed in Heart (15.4) and Peripheral blood mononuclear cells (10.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RRAGA Gene



Protein tissue co-expression partners for RRAGA Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RRAGA

SOURCE GeneReport for Unigene cluster for RRAGA Gene:

Hs.743260

mRNA Expression by UniProt/SwissProt for RRAGA Gene:

Q7L523-RRAGA_HUMAN
Tissue specificity: Ubiquitously expressed with highest levels of expression in skeletal muscle, heart, and brain.

Evidence on tissue expression from TISSUES for RRAGA Gene

  • Nervous system(4.9)
  • Muscle(3.3)
  • Heart(3)
  • Kidney(2.9)
  • Liver(2.9)
  • Intestine(2.6)
  • Pancreas(2.5)
  • Skin(2.4)
  • Spleen(2.3)
  • Blood(2.2)
  • Lymph node(2.1)
  • Stomach(2)
genes like me logo Genes that share expression patterns with RRAGA: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RRAGA Gene

Orthologs for RRAGA Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for RRAGA Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RRAGA 29 30
  • 99.89 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia -- 30
  • 99 (a)
OneToMany
-- 30
  • 97 (a)
OneToMany
RRAGA 29 30
  • 93.61 (n)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 95 (a)
ManyToMany
-- 30
  • 88 (a)
ManyToMany
Mouse
(Mus musculus)
Mammalia Rraga 29 16 30
  • 92.76 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rraga 29
  • 92.55 (n)
Dog
(Canis familiaris)
Mammalia RRAGA 29
  • 92.44 (n)
Chicken
(Gallus gallus)
Aves -- 30
  • 87 (a)
OneToMany
RRAGB 29
  • 84.13 (n)
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 91 (a)
OneToMany
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rraga 29
  • 82.75 (n)
Str.4849 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.3758 29
Zebrafish
(Danio rerio)
Actinopterygii rraga 29 30
  • 79.23 (n)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta RagA 30
  • 77 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea raga-1 30
  • 63 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GTR1 30
  • 52 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.6548 30
  • 73 (a)
OneToMany
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gtr1 29
  • 58.7 (n)
Species where no ortholog for RRAGA was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for RRAGA Gene

ENSEMBL:
Gene Tree for RRAGA (if available)
TreeFam:
Gene Tree for RRAGA (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RRAGA: view image
Alliance of Genome Resources:
Additional Orthologs for RRAGA

Paralogs for RRAGA Gene

Paralogs for RRAGA Gene

(1) SIMAP similar genes for RRAGA Gene using alignment to 1 proteins:

  • RRAGA_HUMAN

Pseudogenes.org Pseudogenes for RRAGA Gene

genes like me logo Genes that share paralogs with RRAGA: view

Variants for RRAGA Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RRAGA Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
rs144684784 Likely Benign: not provided 19,050,568(+) G/C
NM_006570.5(RRAGA):c.909G>C (p.Val303=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RRAGA Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RRAGA Gene

Variant ID Type Subtype PubMed ID
nsv1161845 CNV duplication 26073780

Variation tolerance for RRAGA Gene

Residual Variation Intolerance Score: 24.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.35; 7.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RRAGA Gene

Human Gene Mutation Database (HGMD)
RRAGA
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RRAGA
Leiden Open Variation Database (LOVD)
RRAGA

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RRAGA Gene

Disorders for RRAGA Gene

MalaCards: The human disease database

(2) MalaCards diseases for RRAGA Gene - From: COP

Disorder Aliases PubMed IDs
birt-hogg-dube syndrome
  • bhd
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards
Search RRAGA in MalaCards View complete list of genes associated with diseases

Additional Disease Information for RRAGA

genes like me logo Genes that share disorders with RRAGA: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RRAGA Gene

Publications for RRAGA Gene

  1. Interaction of an adenovirus 14.7-kilodalton protein inhibitor of tumor necrosis factor alpha cytolysis with a new member of the GTPase superfamily of signal transducers. (PMID: 8995684) Li Y … Horwitz MS (Journal of virology 1997) 2 3 4 22
  2. Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. (PMID: 7499430) Schürmann A … Joost HG (The Journal of biological chemistry 1995) 2 3 4
  3. The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity. (PMID: 31036939) Gan L … Meyer T (Nature cell biology 2019) 3 4
  4. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. (PMID: 25567906) Wang S … Sabatini DM (Science (New York, N.Y.) 2015) 3 4
  5. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. (PMID: 25561175) Rebsamen M … Superti-Furga G (Nature 2015) 3 4

Products for RRAGA Gene

Sources for RRAGA Gene