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

Gene ID: 5924, updated on 11-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (80960363..81230162)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (81444995..81714744)
105.20220307 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. 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
  4. RasGRF2 promotes migration and invasion of colorectal cancer cells by modulating expression of MMP9 through Src/Akt/NF-κB pathway. Lu P, et al. Cancer Biol Ther, 2019. PMID 30359168, Free PMC Article
  5. RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release. Stacey D, et al. Proc Natl Acad Sci U S A, 2012 Dec 18. PMID 23223532, Free PMC Article

See all (38) 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)

Genotypes

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 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
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
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_2023_10

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

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