This gene encodes a member of the GTR/RAG GTP-binding protein family. The encoded protein is a monomeric guanine nucleotide-binding protein which forms a heterodimer with RRAGA and RRAGB and is primarily localized to the cytoplasm. The encoded protein promotes intracellular localization of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided... See more...

Aliases for RRAGC Gene

Aliases for RRAGC Gene

  • Ras Related GTP Binding C 2 3 5
  • Ras-Related GTP-Binding Protein C 3 4
  • GTPase-Interacting Protein 2 3 4
  • TIB929 3 4
  • GTR2 2 3
  • Ras-Related GTP Binding C 2
  • Rag C Protein 3
  • EC 3.6.5.- 4
  • FLJ13311 2
  • RRAGC 5
  • Rag C 4
  • RAGC 3
  • RagC 4

External Ids for RRAGC Gene

Previous GeneCards Identifiers for RRAGC Gene

  • GC01M038767
  • GC01M038718
  • GC01M038717
  • GC01M038974
  • GC01M039076
  • GC01M039303
  • GC01M037423
  • GC01M038841
  • GC01M038843
  • GC01M038844
  • GC01M038845

Summaries for RRAGC Gene

Entrez Gene Summary for RRAGC Gene

  • This gene encodes a member of the GTR/RAG GTP-binding protein family. The encoded protein is a monomeric guanine nucleotide-binding protein which forms a heterodimer with RRAGA and RRAGB and is primarily localized to the cytoplasm. The encoded protein promotes intracellular localization of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

GeneCards Summary for RRAGC Gene

RRAGC (Ras Related GTP Binding C) is a Protein Coding gene. Diseases associated with RRAGC include Familial Renal Oncocytoma and Birt-Hogg-Dube Syndrome. Among its related pathways are Macroautophagy and TP53 Regulates Metabolic Genes. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and GTPase activity. An important paralog of this gene is RRAGD.

UniProtKB/Swiss-Prot Summary for RRAGC 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:27234373, 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:27234373, PubMed:24095279). This is a crucial step in the activation of the TOR signaling cascade by amino acids (PubMed:20381137, PubMed:27234373, PubMed:24095279).

Gene Wiki entry for RRAGC Gene

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

Genomics for RRAGC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RRAGC 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 RRAGC on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the RRAGC gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • AP-2gamma
  • C/EBPalpha
  • E47
  • FOXO4
  • SRF
  • SRF (504 AA)
  • Tal-1beta

Genomic Locations for RRAGC Gene

Latest Assembly
chr1:38,838,198-38,859,772
(GRCh38/hg38)
Size:
21,575 bases
Orientation:
Minus strand

Previous Assembly
chr1:39,303,870-39,325,444
(GRCh37/hg19 by Entrez Gene)
Size:
21,575 bases
Orientation:
Minus strand

chr1:39,303,870-39,325,495
(GRCh37/hg19 by Ensembl)
Size:
21,626 bases
Orientation:
Minus strand

Genomic View for RRAGC Gene

Genes around RRAGC on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for RRAGC Gene

Proteins for RRAGC Gene

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

    Protein Symbol:
    Q9HB90-RRAGC_HUMAN
    Recommended name:
    Ras-related GTP-binding protein C
    Protein Accession:
    Q9HB90
    Secondary Accessions:
    • Q9H202
    • Q9H8Q8

    Protein attributes for RRAGC Gene

    Size:
    399 amino acids
    Molecular mass:
    44224 Da
    Quaternary structure:
    • Forms a heterodimer with RRAGA, in a sequence-independent manner, and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization stabilizes proteins of the heterodimer (PubMed:11073942). In complex with RRAGA or 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 (PubMed:31704029, PubMed:31672913). 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 RRAGB, is negatively regulated by amino acids and prevents interaction with RPTOR (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). Interacts with PIP4P1 (By similarity).
    SequenceCaution:
    • Sequence=BAB14548.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RRAGC Gene

neXtProt entry for RRAGC Gene

Post-translational modifications for RRAGC Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for RRAGC Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for RRAGC Gene

Domains & Families for RRAGC Gene

Gene Families for RRAGC Gene

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

Protein Domains for RRAGC Gene

InterPro:
Blocks:
  • Cytosolic fatty-acid binding protein

Suggested Antigen Peptide Sequences for RRAGC Gene

GenScript: Design optimal peptide antigens:
  • Ras-related GTP binding C, isoform CRA_a (D3DPT8_HUMAN)
  • TIB929 (RRAGC_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9HB90

UniProtKB/Swiss-Prot:

RRAGC_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 RRAGC: view

Function for RRAGC Gene

Molecular function for RRAGC 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:27234373, 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:27234373, PubMed:24095279). This is a crucial step in the activation of the TOR signaling cascade by amino acids (PubMed:20381137, PubMed:27234373, PubMed:24095279).
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:0000269|PubMed:11073942, ECO:0000305|PubMed:24095279};.
UniProtKB/Swiss-Prot EnzymeRegulation:
In high-amino acid conditions, activated by GTPase activating protein (GAP) FLCN that stimulates RRAGC GTPase activity to turn it into its active GDP-bound form.

Enzyme Numbers (IUBMB) for RRAGC Gene

Phenotypes From GWAS Catalog for RRAGC Gene

Gene Ontology (GO) - Molecular Function for RRAGC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0000287 magnesium ion binding NAS 11073942
GO:0003924 GTPase activity IBA,IDA 11073942
GO:0005515 protein binding IPI 11073942
GO:0005525 GTP binding IDA,IMP 22424946
genes like me logo Genes that share ontologies with RRAGC: view
genes like me logo Genes that share phenotypes with RRAGC: view

miRNA for RRAGC Gene

miRTarBase miRNAs that target RRAGC

Inhibitory RNAs for research

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

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for RRAGC Gene

Localization for RRAGC Gene

Subcellular locations from UniProtKB/Swiss-Prot for RRAGC Gene

Cytoplasm. Nucleus. Lysosome. Note=Predominantly cytoplasmic. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state of associated RRAGA (PubMed:11073942). {ECO:0000269 PubMed:11073942}.

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 RRAGC gene
Compartment Confidence
nucleus 5
cytosol 5
lysosome 5
endosome 4
plasma membrane 2
mitochondrion 2
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RRAGC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 11073942
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA,IDA 11073942
GO:0005764 lysosome IBA,IDA 20381137
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with RRAGC: view

Pathways & Interactions for RRAGC Gene

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

Pathways by source for RRAGC Gene

SIGNOR curated interactions for RRAGC Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for RRAGC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated NAS 11073942
GO:0006915 apoptotic process NAS 11073942
GO:0007050 cell cycle arrest TAS --
GO:0007264 small GTPase mediated signal transduction TAS 11073942
GO:0008380 RNA splicing NAS 11073942
genes like me logo Genes that share ontologies with RRAGC: view

Drugs & Compounds for RRAGC Gene

(3) Drugs for RRAGC 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 RRAGC: view

Transcripts for RRAGC Gene

mRNA/cDNA for RRAGC Gene

2 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
4 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 RRAGC

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

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c · 6d ^ 7a · 7b
SP1: -
SP2: - -
SP3: - -
SP4:

Relevant External Links for RRAGC Gene

GeneLoc Exon Structure for
RRAGC

Expression for RRAGC Gene

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

Protein differential expression in normal tissues from HIPED for RRAGC Gene

This gene is overexpressed in Liver (24.6), Amniocyte (12.7), and Peripheral blood mononuclear cells (6.9).

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



Protein tissue co-expression partners for RRAGC Gene

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

SOURCE GeneReport for Unigene cluster for RRAGC Gene:

Hs.532461

Evidence on tissue expression from TISSUES for RRAGC Gene

  • Liver(4.4)
  • Pancreas(3.6)
  • Nervous system(2.5)
  • Kidney(2.4)
  • Skin(2.3)
  • Muscle(2.2)
  • Blood(2.1)
genes like me logo Genes that share expression patterns with RRAGC: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for RRAGC Gene

Orthologs for RRAGC Gene

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

Orthologs for RRAGC Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RRAGC 29 30
  • 99.3 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RRAGC 29 30
  • 96.24 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RRAGC 29 30
  • 95.32 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rragc 29 16 30
  • 92.04 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia RRAGC 30
  • 92 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rragc 29
  • 90.79 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia RRAGC 30
  • 83 (a)
OneToOne
Chicken
(Gallus gallus)
Aves RRAGC 29 30
  • 81.54 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RRAGC 30
  • 90 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia rragc 29
  • 79.49 (n)
Str.16064 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.7005 29
Zebrafish
(Danio rerio)
Actinopterygii rragcb 30
  • 82 (a)
OneToMany
rragca 29 30
  • 75.18 (n)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta RagC 29 30
  • 67.41 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP007634 29
  • 65.35 (n)
Worm
(Caenorhabditis elegans)
Secernentea ragc-1 29 30
  • 54.51 (n)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GTR2 30 32
  • 45 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9757 30
  • 65 (a)
OneToMany
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gtr2 29
  • 63.38 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU00376 29
  • 54.47 (n)
Species where no ortholog for RRAGC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • 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)
  • 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 RRAGC Gene

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

Paralogs for RRAGC Gene

Paralogs for RRAGC Gene

(1) SIMAP similar genes for RRAGC Gene using alignment to 2 proteins:

  • RRAGC_HUMAN
  • D3DPT8_HUMAN
genes like me logo Genes that share paralogs with RRAGC: view

Variants for RRAGC Gene

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

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
VAR_076511 -- p.Ser75Tyr

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

Variant ID Type Subtype PubMed ID
nsv1078344 CNV deletion 25765185

Variation tolerance for RRAGC Gene

Residual Variation Intolerance Score: 34% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.30; 6.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RRAGC Gene

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

SNP Genotyping and Copy Number Assays for research

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

Disorders for RRAGC Gene

MalaCards: The human disease database

(3) MalaCards diseases for RRAGC Gene - From: COP and GCD

Disorder Aliases PubMed IDs
familial renal oncocytoma
birt-hogg-dube syndrome
  • bhd
dilated cardiomyopathy
  • congestive cardiomyopathy
- elite association - COSMIC cancer census association via MalaCards
Search RRAGC in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RRAGC_HUMAN
  • Note=RRAGC mutations have been found in a patient with idiopathic dilated cardiomyopathy with ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms. {ECO:0000269 PubMed:27234373}.

Additional Disease Information for RRAGC

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

No data available for Genatlas for RRAGC Gene

Publications for RRAGC Gene

  1. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. (PMID: 11073942) Sekiguchi T … Nishimoto T (The Journal of biological chemistry 2001) 2 3 4
  2. De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy. (PMID: 27234373) Long PA … Olson TM (Human genetics 2016) 3 4
  3. 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
  4. 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
  5. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. (PMID: 25259925) Peng M … Li MO (Cell 2014) 3 4

Products for RRAGC Gene

Sources for RRAGC Gene