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    RASGRF2 Ras protein-specific guanine nucleotide-releasing factor 2 [ Homo sapiens ]

    Gene ID: 5924, updated on 11-May-2012
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    Summary

    Official Symbol
    RASGRF2provided by HGNC
    Official Full Name
    Ras protein-specific guanine nucleotide-releasing factor 2provided by HGNC
    Primary source
    HGNC:9876
    See related
    Ensembl:ENSG00000113319; HPRD:07588; MIM:606614; Vega:OTTHUMG00000119015
    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; DKFZp781H1715
    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]
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    Genomic context

    Location :
    5q13
    Sequence :
    Chromosome: 5; NC_000005.9 (80256558..80521953)
    See RASGRF2 in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene MT-RNR2-like 2 Neighboring gene dihydrofolate reductase Neighboring gene mutS homolog 3 (E. coli) Neighboring gene ribosomal protein S26 pseudogene 27 Neighboring gene uncharacterized LOC100131067 Neighboring gene creatine kinase, mitochondrial 2 (sarcomeric) Neighboring gene zinc finger, CCHC domain containing 9

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation. Calvo F, et al. Nat Cell Biol, 2011 Jun 19. PMID 21685891.
    2. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Rose JE, et al. Mol Med, 2010 Jul-Aug. PMID 20379614.
    3. The use of knockout mice reveals a synergistic role of the Vav1 and Rasgrf2 gene deficiencies in lymphomagenesis and metastasis. Ruiz S, et al. PLoS One, 2009 Dec 14. PMID 20011522.
    4. Structural and spatial determinants regulating TC21 activation by RasGRF family nucleotide exchange factors. Calvo F, et al. Mol Biol Cell, 2009 Oct. PMID 19692568.
    5. Toward a confocal subcellular atlas of the human proteome. Barbe L, et al. Mol Cell Proteomics, 2008 Mar. PMID 18029348.

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. 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.
    2. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    3. Farnesylated but not geranylgeranylated TC21 can be activated by RasGRF2 due to its pleckstrin homology 1 domain, by a mechanism independent of localization & of its ability to associate to membranes.
      Title: Structural and spatial determinants regulating TC21 activation by RasGRF family nucleotide exchange factors.
    4. These data reveal unexpected negative roles for Vav1 and RasGRF2 in different stages of T-cell lymphoma progression.
      Title: The use of knockout mice reveals a synergistic role of the Vav1 and Rasgrf2 gene deficiencies in lymphomagenesis and metastasis.
    5. These results identify RasGRF2 as an additional component of the signaling machinery involved in T-cell receptor- and NF-AT-mediated immune responses.
      Title: RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses.
    6. RasGRF family exchange factors, both endogenous and ectopically expressed, are present in the endoplasmic reticulum but not in the Golgi complex
      Title: Activation of H-Ras in the endoplasmic reticulum by the RasGRF family guanine nucleotide exchange factors.
    7. Aberrant methylation of RASGRF2 is associated with human non-small cell lung cancer
      Title: Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer.
    Submit: New GeneRIF Correction
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    BioGRID:111859 BioGRID:123666 EPPK1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111859 BioGRID:110043 KRAS    BioGRID  PubMed Reconstituted Complex 
    BioGRID:111859 BioGRID:123079 PANK2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111859 BioGRID:115897 PMVK    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111859 BioGRID:111859 RASGRF2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111859 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Activation of NMDA receptor upon glutamate binding and postsynaptic events, organism-specific biosystem (from REACTOME)
      Activation of NMDA receptor upon glutamate binding and postsynaptic events, organism-specific biosystemNMDA receptors are a subtype of ionotropic glutamate receptors that are specifically activated by a glutamate agonist N-methyl-D-aspartate (NMDA). Activation of NMDA receptor involves opening of the ...
    • CREB phosphorylation through the activation of Ras, organism-specific biosystem (from REACTOME)
      CREB phosphorylation through the activation of Ras, organism-specific biosystemCa2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca...
    • Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
      Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
    • G alpha (12/13) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (12/13) signalling events, organism-specific biosystemThe G12/13 family is probably the least well characterized subtype, partly because G12/13 coupling is difficult to determine when compared with the other subtypes which predominantly rely on assay te...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • NRAGE signals death through JNK, organism-specific biosystem (from REACTOME)
      NRAGE signals death through JNK, organism-specific biosystemOnce bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pr...
    • Neuronal System, organism-specific biosystem (from REACTOME)
      Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
    • Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystem (from REACTOME)
      Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell, organism-specific biosystemThe neurotransmitter in the synaptic cleft released by the pre-synaptic neuron binds specific receptors located on the post-synaptic terminal. These receptors are either ion channels or G protein cou...
    • Post NMDA receptor activation events, organism-specific biosystem (from REACTOME)
      Post NMDA receptor activation events, organism-specific biosystemCa2+ influx through the NMDA receptor initiates subsequent molecular pathways that have a defined role in establishing long-lasting synaptic changes. The molecular signaling initiated by a rise in Ca...
    • Ras activation uopn Ca2+ infux through NMDA receptor, organism-specific biosystem (from REACTOME)
      Ras activation uopn Ca2+ infux through NMDA receptor, organism-specific biosystemCa2+ influx through the NMDA receptor leads to the activation of Ras kinase via the activation of RasGRF.
    • Regulation of RAC1 activity, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of RAC1 activity, organism-specific biosystem
      Regulation of RAC1 activity
    • Rho GTPase cycle, organism-specific biosystem (from REACTOME)
      Rho GTPase cycle, organism-specific biosystemThe cycling of Rho GTPases is tightly controlled by three classes of protein. These are (1) guanine nucleotide dissociation inhibitors or GDIs, which maintain Rho proteins in an inactive state in the...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
      Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
      Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...
    • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
      p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    Rho guanyl-nucleotide exchange factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    guanyl-nucleotide exchange factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    apoptotic process TAS
    Traceable Author Statement
    more info
    		  
    induction of apoptosis by extracellular signals TAS
    Traceable Author Statement
    more info
    		  
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    regulation of Rho protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    synaptic transmission TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    ras-specific guanine nucleotide-releasing factor 2
    Names
    ras-specific guanine nucleotide-releasing factor 2
    ras guanine nucleotide exchange factor 2
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    NCBI Reference Sequences (RefSeq)

    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
      5001..274474
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      Status: REVIEWED

      Source sequence(s)
      BC041953, BC136296, BU430075, BX502901, CR749239, DA219722, DA230428
      Consensus CDS
      CCDS4052.1
      UniProtKB/Swiss-Prot
      O14827
      UniProtKB/TrEMBL
      Q68DX5
      Related
      ENSP00000265080, OTTHUMP00000147545, ENST00000265080, OTTHUMT00000239215
      Conserved Domains (4) summary
      cd00155
      Location:998 – 1230
      Blast Score: 656
      RasGEF; Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. ...
      cd00160
      Location:244 – 427
      Blast Score: 316
      RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.
      cd06224
      Location:643 – 689
      Blast Score: 123
      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 ...
      cd00821
      Location:25 – 131
      Blast Score: 142
      PH; Pleckstrin homology (PH) domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      80256558..80521953
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      75465417..75730872
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC020901.8 (15068..108256) None
    genomic AC026427.4 None
    genomic CH471084.1 EAW95863.1
    genomic CQ834808.1 CAH05619.1
    mRNA AF023130.1 AAB80953.1
    mRNA AF181250.1 AAD55268.1
    mRNA AK094809.1 None
    mRNA AL598102.1 None
    mRNA BC041953.1 None
    mRNA BC126112.1 AAI26113.1
    mRNA BC136296.1 AAI36297.1
    mRNA BC143870.1 None
    mRNA BU430075.1 None
    mRNA BX502901.1 None
    mRNA CR749239.1 CAH18095.1
    mRNA DA219722.1 None
    mRNA DA230428.1 None
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14827.2 GenPept UniProtKB/Swiss-Prot:O14827
    Q68DX5 GenPept UniProtKB/TrEMBL:Q68DX5
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    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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