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    ARHGEF3 Rho guanine nucleotide exchange factor (GEF) 3 [ Homo sapiens ]

    Gene ID: 50650, updated on 11-May-2012
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    Summary

    Official Symbol
    ARHGEF3provided by HGNC
    Official Full Name
    Rho guanine nucleotide exchange factor (GEF) 3provided by HGNC
    Primary source
    HGNC:683
    See related
    Ensembl:ENSG00000163947; HPRD:12480; MIM:612115; Vega:OTTHUMG00000158857
    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
    GEF3; STA3; XPLN; FLJ98126; MGC118905; DKFZp434F2429
    Summary
    Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    3p21-p13
    Sequence :
    Chromosome: 3; NC_000003.11 (56761446..57113336, complement)
    See ARHGEF3 in Epigenomics, MapViewer

    Chromosome 3 - NC_000003.11Genomic Context describing neighboring genes Neighboring gene ELKS/RAB6-interacting/CAST family member 2 Neighboring gene microRNA 3938 Neighboring gene coiled-coil domain containing 66 Neighboring gene family with sequence similarity 208, member A Neighboring gene spermatogenesis associated 12 Neighboring gene interleukin 17 receptor D Neighboring gene ribosomal protein L19 pseudogene 2 Neighboring gene HESX homeobox 1

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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. Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci. Freudenberg J, et al. Arthritis Rheum, 2011 Apr. PMID 21452313.
    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. Mutation of ARHGAP9 in patients with coronary spastic angina. Takefuji M, et al. J Hum Genet, 2010 Jan. PMID 19911011.
    4. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Soranzo N, et al. Nat Genet, 2009 Nov. PMID 19820697.
    5. Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women. Li GH, et al. Osteoporos Int, 2010 Jun. PMID 19727905.

    See all (26) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

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

    1. the association between rs7646054 in ARHGEF3 and bone mineral density observed in Caucasians was not replicated in the chinese samples.
      Title: Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with osteoporosis in southern Chinese women.
    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. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: A genome-wide association study identifies three loci associated with mean platelet volume.
    4. genetic variation in ARHGEF3 plays a role in the determination of bone density in Caucasian women. This data implicates the RhoGTPase-RhoGEF pathway in osteoporosis.
      Title: Identification of a role for the ARHGEF3 gene in postmenopausal osteoporosis.
    5. Observational study of gene-disease association. (HuGE Navigator)
      Title: Mutation of ARHGAP9 in patients with coronary spastic angina.
    6. a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC
      Title: XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC.
    Submit: New GeneRIF Correction
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    A genome-wide association study identifies three loci associated with mean platelet volume.

    A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.

    Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci.

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q9NR81 P61586 RHOA    HPRD  PubMed  
    Q9NR81 P62745 RHOB    HPRD  PubMed  
    BioGRID:119115 BioGRID:106880 RHOA    BioGRID  PubMed Biochemical Activity; Reconstituted Complex 
    BioGRID:119115 BioGRID:106881 RHOB    BioGRID  PubMed Biochemical Activity; Reconstituted Complex 
    BioGRID:119115 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:119115 BioGRID:132223 SUMO4    BioGRID  PubMed Affinity Capture-Western 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • 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...
    • 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...
    • Regulation of RhoA activity, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of RhoA activity, organism-specific biosystem
      Regulation of RhoA 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...
    • 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
    		  
    guanyl-nucleotide exchange factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    Rho protein signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    intracellular IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    rho guanine nucleotide exchange factor 3
    Names
    rho guanine nucleotide exchange factor 3
    RhoGEF protein
    59.8 kDA protein
    exchange factor found in platelets and leukemic and neuronal tissues, XPLN
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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.

    mRNA and Protein(s)

    1. NM_001128615.1 → NP_001122087.1  rho guanine nucleotide exchange factor 3 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF433662, AL136832, DC334772
      Consensus CDS
      CCDS46854.1
      UniProtKB/Swiss-Prot
      Q9NR81
      Related
      ENSP00000341071, OTTHUMP00000213599, ENST00000338458, OTTHUMT00000352432
      Conserved Domains (2) summary
      cd00160
      Location:155 – 334
      Blast Score: 326
      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.
      cd00821
      Location:371 – 479
      Blast Score: 83
      PH; Pleckstrin homology (PH) domain

    2. NM_001128616.1 → NP_001122088.1  rho guanine nucleotide exchange factor 3 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1.
      Source sequence(s)
      AB209661, AF433662, AL136832, DC334437
      Consensus CDS
      CCDS46855.1
      UniProtKB/Swiss-Prot
      Q9NR81
      Related
      ENSP00000410922, OTTHUMP00000213600, ENST00000413728, OTTHUMT00000352433
      Conserved Domains (2) summary
      cd00160
      Location:129 – 308
      Blast Score: 324
      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.
      cd00821
      Location:345 – 453
      Blast Score: 82
      PH; Pleckstrin homology (PH) domain

    3. NM_019555.2 → NP_062455.1  rho guanine nucleotide exchange factor 3 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (3) has a distinct and shorter N-terminus, as compared to isoform 1.
      Source sequence(s)
      AF433662, AL136832, DA401228
      Consensus CDS
      CCDS2878.1
      UniProtKB/Swiss-Prot
      Q9NR81
      Related
      ENSP00000296315, OTTHUMP00000213598, ENST00000296315, OTTHUMT00000352431
      Conserved Domains (2) summary
      cd00160
      Location:123 – 302
      Blast Score: 325
      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.
      cd00821
      Location:337 – 447
      Blast Score: 84
      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_000003.11 Reference GRCh37.p5 Primary Assembly

      Range
      56761446..57113336, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000135.1 Alternate HuRef

      Range
      56809905..57161427, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC097358.2 (16657..40166) None
    genomic AC099327.2 (80583..184038) None
    genomic AC099559.2 (5438..12333) None
    genomic AC099781.2 (133092..200703) None
    genomic AX002254.1 None
    genomic CH471055.1 EAW65325.1
      EAW65326.1
    mRNA AB209661.1 BAD92898.1
    mRNA AF249744.1 AAF79954.1
    mRNA AF433662.1 AAP97313.1
    mRNA AK024340.1 BAB14891.1
    mRNA AK225688.1 None
    mRNA AK291412.1 BAF84101.1
    mRNA AK293864.1 BAH11616.1
    mRNA AK300045.1 BAH13198.1
    mRNA AK302493.1 BAH13724.1
    mRNA AK308178.1 None
    mRNA AL136832.1 CAB66766.1
    mRNA AX775923.1 CAE11661.1
    mRNA BC022249.1 None
    mRNA BC054345.1 AAH54345.2
    mRNA BC068513.1 AAH68513.1
    mRNA BC094748.1 None
    mRNA BC098122.1 AAH98122.2
    mRNA BC098272.1 AAH98272.2
    mRNA BC099715.1 AAH99715.1
    mRNA BC104723.1 AAI04724.2
    mRNA DA401228.1 None
    mRNA DC334437.1 None
    mRNA DC334772.1 None
    other-genetic AM392996.1 CAL37874.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NR81.1 GenPept UniProtKB/Swiss-Prot:Q9NR81
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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
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