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    RASGRF2 Ras protein specific guanine nucleotide releasing factor 2 [ Homo sapiens (human) ]

    Gene ID: 5924, updated on 27-Nov-2024

    Summary

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    Official Symbol
    RASGRF2provided by HGNC
    Official Full Name
    Ras protein specific guanine nucleotide releasing factor 2provided by HGNC
    Primary source
    HGNC:HGNC:9876
    See related
    Ensembl:ENSG00000113319 MIM:606614; AllianceGenome:HGNC:9876
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GRF2; RAS-GRF2
    Summary
    RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]
    Expression
    Broad expression in brain (RPKM 9.6), ovary (RPKM 7.2) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RASGRF2 in Genome Data Viewer
    Location:
    5q14.1
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (80960363..81230162)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (81444995..81714744)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (80256182..80525981)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene mutS homolog 3 Neighboring gene uncharacterized LOC107986428 Neighboring gene ribosomal protein S26 pseudogene 27 Neighboring gene RASGRF2 antisense RNA 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr5:80252674-80253194 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:80256285-80257006 Neighboring gene Sharpr-MPRA regulatory region 14075 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22729 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:80487900-80488408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:80488409-80488915 Neighboring gene uncharacterized LOC124901017 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22730 Neighboring gene CKMT2 antisense RNA 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr5:80564272-80565471 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:80565548-80566100 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:80566101-80566651 Neighboring gene MPRA-validated peak5313 silencer Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:80597135-80597924 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:80597925-80598714 Neighboring gene creatine kinase, mitochondrial 2 Neighboring gene zinc finger CCHC-type containing 9 Neighboring gene acyl-CoA thioesterase 12

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model. Karamitros T, et al. Proc Natl Acad Sci U S A, 2018 Oct 9. PMID 30249655, Free PMC Article
    2. A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men. Novo-Veleiro I, et al. PLoS One, 2016. PMID 27992614, Free PMC Article
    3. Mapping of the Ras-GRF2 gene (GRF2) to mouse chromosome 13C3-D1 and human chromosome 5q13, near the Ras-GAP gene. Fam NP, et al. Genomics, 1997 Jan 1. PMID 9027497
    4. Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange factor for Ras. Fam NP, et al. Mol Cell Biol, 1997 Mar. PMID 9032266, Free PMC Article
    5. Reciprocal expression of Annexin A6 and RasGRF2 discriminates rapidly growing from invasive triple negative breast cancer subsets. Korolkova OY, et al. PLoS One, 2020. PMID 32298357, Free PMC Article

    See all (40) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.
      Title: Genetic variants of SOS2, MAP2K1 and RASGRF2 in the RAS pathway genes predict survival of HBV-related hepatocellular carcinoma patients.
    2. AnxA6 may be a reliable biomarker for distant relapse-free survival and response of triple negative breast cancer (TNBC) patients to chemotherapy, and that the reciprocal expression of AnxA6 and GRF2 can reliably delineate TNBCs into rapidly growing and invasive subsets which may be more relevant for subset-specific therapeutic interventions.
      Title: Reciprocal expression of Annexin A6 and RasGRF2 discriminates rapidly growing from invasive triple negative breast cancer subsets.
    3. High RASGRF2 expression is associated with migration and invasion of colorectal cancer.
      Title: RasGRF2 promotes migration and invasion of colorectal cancer cells by modulating expression of MMP9 through Src/Akt/NF-κB pathway.
    4. RASGRF2-int is significantly associated with drug addiction.
      Title: Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model.
    5. this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with Alcoholic Liver Cirrhosis in men, particularly in the subgroup of patients with alcohol dependence. The findings suggest the potential relevance of the RAS gene family in alcoholism and Alcoholic Liver Cirrhosis.
      Title: A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men.
    6. Endoplasmic reticulum stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF.
      Title: RasGRF Couples Nox4-Dependent Endoplasmic Reticulum Signaling to Ras.
    7. these results suggest that betaarrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion.
      Title: βArrestin1 regulates the guanine nucleotide exchange factor RasGRF2 expression and the small GTPase Rac-mediated formation of membrane protrusion and cell motility.
    8. Case-control studies reveal malignant mesothelioma risk associated with variants in the SDK1, CRTAM and RASGRF2 genes.
      Title: A genome-wide association study for malignant mesothelioma risk.
    9. RASGRF2 has a role in the regulation of mesolimbic dopamine neuron activity, reward response, and alcohol use and abuse
      Title: RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release.
    10. Demonstrate a role for RasGRF1/2 as negative regulators of Cdc42 activation, suppressing tumor cell movement, cytoskeletal dynamics and cell transformation.
      Title: RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    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

    EBI GWAS Catalog

    Description
    Common variants at 1p36 are associated with superior frontal gyrus volume.
    EBI GWAS Catalog
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts.
    EBI GWAS Catalog
    Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Clone Names

    • DKFZp781H1715

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables guanyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables guanyl-nucleotide exchange factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in Ras protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in postsynaptic modulation of chemical synaptic transmission IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    involved_in response to endoplasmic reticulum stress IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		  
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in glutamatergic synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynapse IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ras-specific guanine nucleotide-releasing factor 2
    Names
    ras guanine nucleotide exchange factor 2

    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.

    Genomic

    1. NG_030334.1 RefSeqGene

      Range
      4675..274474
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006909.3 → NP_008840.1  ras-specific guanine nucleotide-releasing factor 2

      See identical proteins and their annotated locations for NP_008840.1

      Status: REVIEWED

      Source sequence(s)
      AC026427, BC041953, BC136296, BU430075, BX502901, CR749239, DA219722, DA230428
      Consensus CDS
      CCDS4052.1
      UniProtKB/Swiss-Prot
      B9EG89, O14827, Q9UK56
      UniProtKB/TrEMBL
      A0A2X0SFL3, D6RAS9
      Related
      ENSP00000265080.4, ENST00000265080.9
      Conserved Domains (6) summary
      smart00147
      Location:998 → 1234
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases
      smart00229
      Location:901 → 972
      RasGEFN; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif
      smart00233
      Location:480 → 588
      PH; Pleckstrin homology domain
      smart00325
      Location:247 → 428
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases
      cd13261
      Location:19 → 158
      PH_RasGRF1_2; Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain
      pfam00618
      Location:638 → 686
      RasGEF_N; RasGEF N-terminal motif

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      80960363..81230162
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005248565.2 → XP_005248622.1  ras-specific guanine nucleotide-releasing factor 2 isoform X3

      UniProtKB/TrEMBL
      D6RAS9
      Conserved Domains (6) summary
      smart00233
      Location:480 → 588
      PH; Pleckstrin homology domain
      cd13261
      Location:19 → 158
      PH_RasGRF1_2; Ras-specific guanine nucleotide-releasing factors 1 and 2 Pleckstrin homology (PH) domain
      pfam00169
      Location:24 → 133
      PH; PH domain
      pfam00618
      Location:638 → 686
      RasGEF_N; RasGEF N-terminal motif
      pfam00621
      Location:247 → 428
      RhoGEF; RhoGEF domain
      cl02520
      Location:901 → 931
      REM; Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately ...

    2. XM_017009683.2 → XP_016865172.1  ras-specific guanine nucleotide-releasing factor 2 isoform X4

    3. XM_047417464.1 → XP_047273420.1  ras-specific guanine nucleotide-releasing factor 2 isoform X1

    4. XM_047417463.1 → XP_047273419.1  ras-specific guanine nucleotide-releasing factor 2 isoform X1

    5. XM_047417466.1 → XP_047273422.1  ras-specific guanine nucleotide-releasing factor 2 isoform X2

    6. XM_047417465.1 → XP_047273421.1  ras-specific guanine nucleotide-releasing factor 2 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      81444995..81714744
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353040.1 → XP_054209015.1  ras-specific guanine nucleotide-releasing factor 2 isoform X3

    2. XM_054353041.1 → XP_054209016.1  ras-specific guanine nucleotide-releasing factor 2 isoform X4

    3. XM_054353037.1 → XP_054209012.1  ras-specific guanine nucleotide-releasing factor 2 isoform X1

    4. XM_054353036.1 → XP_054209011.1  ras-specific guanine nucleotide-releasing factor 2 isoform X1

    5. XM_054353039.1 → XP_054209014.1  ras-specific guanine nucleotide-releasing factor 2 isoform X2

    6. XM_054353038.1 → XP_054209013.1  ras-specific guanine nucleotide-releasing factor 2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14827.2 GenPept UniProtKB/Swiss-Prot:O14827

    Gene LinkOut

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

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