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    RRAGA Ras related GTP binding A [ Homo sapiens (human) ]

    Gene ID: 10670, updated on 5-Mar-2024

    Summary

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    Official Symbol
    RRAGAprovided by HGNC
    Official Full Name
    Ras related GTP binding Aprovided by HGNC
    Primary source
    HGNC:HGNC:16963
    See related
    Ensembl:ENSG00000155876 MIM:612194; AllianceGenome:HGNC:16963
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FIP1; RAGA; FIP-1
    Summary
    Enables several functions, including GTP binding activity; protein dimerization activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular response to amino acid starvation; negative regulation of autophagy; and positive regulation of TORC1 signaling. Located in lysosome and nucleus. Colocalizes with GATOR1 complex. [provided by Alliance of Genome Resources, Apr 2022]
    Orthologs
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    Genomic context

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    Location:
    9p22.1
    Exon count:
    1
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (19049427..19051025)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (19062292..19063890)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (19049425..19051023)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene ADAMTS like 1 Neighboring gene uncharacterized LOC105375985 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:19032529-19033082 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:19033083-19033636 Neighboring gene stabilizer of axonemal microtubules 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr9:19049365-19049886 Neighboring gene proteasome 26S subunit, ATPase 3 pseudogene 1 Neighboring gene RNA, U6 small nuclear 264, pseudogene Neighboring gene small Cajal body-specific RNA 8 Neighboring gene HAUS augmin like complex subunit 6

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. RAGA prevents tumor immune evasion of LUAD by promoting CD47 lysosome degradation. Zhang L, et al. Commun Biol, 2023 Feb 23. PMID 36823443, Free PMC Article
    2. Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes. Shen K, et al. Nature, 2018 Apr 5. PMID 29590090, Free PMC Article
    3. Mutations of RagA GTPase in mTORC1 Pathway Are Associated with Autosomal Dominant Cataracts. Chen JH, et al. PLoS Genet, 2016 Jun. PMID 27294265, Free PMC Article
    4. An interdomain hydrogen bond in the Rag GTPases maintains stable mTORC1 signaling in sensing amino acids. Egri SB, et al. J Biol Chem, 2021 Jul. PMID 34116056, Free PMC Article
    5. C9orf72 associates with inactive Rag GTPases and regulates mTORC1-mediated autophagosomal and lysosomal biogenesis. Wang M, et al. Aging Cell, 2020 Apr. PMID 32100453, Free PMC Article

    See all (77) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RAGA prevents tumor immune evasion of LUAD by promoting CD47 lysosome degradation.
      Title: RAGA prevents tumor immune evasion of LUAD by promoting CD47 lysosome degradation.
    2. Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.
      Title: Structure of the lysosomal mTORC1-TFEB-Rag-Ragulator megacomplex.
    3. An interdomain hydrogen bond in the Rag GTPases maintains stable mTORC1 signaling in sensing amino acids.
      Title: An interdomain hydrogen bond in the Rag GTPases maintains stable mTORC1 signaling in sensing amino acids.
    4. C9orf72 associates with inactive Rag GTPases and regulates mTORC1-mediated autophagosomal and lysosomal biogenesis.
      Title: C9orf72 associates with inactive Rag GTPases and regulates mTORC1-mediated autophagosomal and lysosomal biogenesis.
    5. The Rag GTPase Regulates the Dynamic Behavior of TSC Downstream of Both Amino Acid and Growth Factor Restriction.
      Title: The Rag GTPase Regulates the Dynamic Behavior of TSC Downstream of Both Amino Acid and Growth Factor Restriction.
    6. Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation.
      Title: Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation.
    7. Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9.
      Title: Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9.
    8. cryo-electron microscopy structure of RagA/RagC in complex with mTORC1 shows the details of RagA/RagC binding to the RAPTOR subunit of mTORC1 and explains why only the RagAGTP/RagCGDP nucleotide state binds mTORC1
      Title: Architecture of human Rag GTPase heterodimers and their complex with mTORC1.
    9. The Raptor alpha-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling.
      Title: Structural basis for the docking of mTORC1 on the lysosomal surface.
    10. PR137B-knockout cells exhibited defective autophagy and an expanded lysosome compartment, similar to Rag-knockout cells. Like zebrafish RagA mutants, GPR137B-mutant zebrafish had upregulated TFEB target gene expression and an expanded lysosome compartment in microglia.
      Title: The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify ras-related GTP binding protein A (RRAGA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify ras-related GTP binding protein A (RRAGA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify ras-related GTP binding protein A (RRAGA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify ras-related GTP binding protein A (RRAGA), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTP binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables GTPase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTPase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphoprotein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein-membrane adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to amino acid starvation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to amino acid stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to nutrient levels IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to starvation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glucose homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of autophagy IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of autophagy IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of TOR signaling NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of TORC1 signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of TORC1 signaling IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of TORC1 signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein localization to lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein localization to membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in tumor necrosis factor-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of FNIP-folliculin RagC/D GAP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of GATOR1 complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of Gtr1-Gtr2 GTPase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in lysosomal membrane HDA PubMed 
    is_active_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ras-related GTP-binding protein A
    Names
    adenovirus E3 14.7 kDa-interacting protein 1
    adenovirus E3-14.7K interacting protein 1
    rag A

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_006570.5 → NP_006561.1  ras-related GTP-binding protein A

      See identical proteins and their annotated locations for NP_006561.1

      Status: VALIDATED

      Source sequence(s)
      BC009990, BX346838
      Consensus CDS
      CCDS6488.1
      UniProtKB/Swiss-Prot
      B2R7L1, O00290, Q15347, Q7L523
      Related
      ENSP00000369899.1, ENST00000380527.3
      Conserved Domains (1) summary
      cd11384
      Location:9 → 292
      RagA_like; Rag GTPase, subfamily of Ras-related GTPases, includes Ras-related GTP-binding proteins A and B

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      19049427..19051025
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      19062292..19063890
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q7L523.1 GenPept UniProtKB/Swiss-Prot:Q7L523

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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