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    ARHGAP4 Rho GTPase activating protein 4 [ Homo sapiens (human) ]

    Gene ID: 393, updated on 5-May-2013
    Official Symbol
    ARHGAP4provided by HGNC
    Official Full Name
    Rho GTPase activating protein 4provided by HGNC
    Primary source
    HGNC:674
    See related
    Ensembl:ENSG00000089820; HPRD:02063; MIM:300023; Vega:OTTHUMG00000024226
    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
    C1; RGC1; p115; SrGAP4; RhoGAP4
    Summary
    This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins belonging to the RAS superfamily. The protein encoded by the orthologous gene in rat is localized to the Golgi complex and can redistribute to microtubules. The rat protein stimulates the activity of some Rho GTPases in vitro. Genomic deletions of this gene and a neighboring gene have been found in patients with nephrogenic diabetes insipidus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
    Location :
    Xq28
    Sequence :
    Chromosome: X; NC_000023.10 (153172830..153191714, complement)
    See ARHGAP4 in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic Context describing neighboring genes Neighboring gene putative lung carcinoma-associated protein 10-like Neighboring gene arginine vasopressin receptor 2 Neighboring gene N(alpha)-acetyltransferase 10, NatA catalytic subunit Neighboring gene renin binding protein

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Proteomic investigation of the interactome of FMNL1 in hematopoietic cells unveils a role in calcium-dependent membrane plasticity. Han Y, et al. J Proteomics, 2013 Jan 14. PMID 23182705.
    2. A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability. Huang L, et al. Am J Med Genet A, 2012 Oct. PMID 22965914.
    3. Multiple myeloma-associated chromosomal translocation activates orphan snoRNA ACA11 to suppress oxidative stress. Chu L, et al. J Clin Invest, 2012 Aug 1. PMID 22751105.
    4. PRL-1 protein promotes ERK1/2 and RhoA protein activation through a non-canonical interaction with the Src homology 3 domain of p115 Rho GTPase-activating protein. Bai Y, et al. J Biol Chem, 2011 Dec 9. PMID 22009749.
    5. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.

    See all (29) 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. X-linked nephrogenic diabetes insipidus (NDI) and intellectual disability in two dizygotic twin brothers was caused by a novel contiguous deletion of 17,905 bp of the entire AVPR2 gene and intron 7 of the ARHGAP4 gene.
      Title: A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability.
    2. PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/2 and RhoA activation
      Title: PRL-1 protein promotes ERK1/2 and RhoA protein activation through a non-canonical interaction with the Src homology 3 domain of p115 Rho GTPase-activating protein.
    3. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    5. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of ARHGAP4 does not result in clinical immunodeficiency
      Title: Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes.
    6. A novel type of contiguous gene deletion of ARHGAP4 has been identified in unrelated Japanese kindreds with nephrogenic diabetes insipidus.
      Title: Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus.
    7. FNBP2, ARHGAP13, ARHGAP14 and ARHGAP4 constitute the FNBP2 family characterized by FCH, RhoGAP and SH3 domains.
      Title: FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains.
    Submit: New GeneRIF Correction

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    NP_001657.2     BIND  PubMed ARHGAP4 interacts with Rac1-GTP This interaction was modeled on a demonstrated interaction between rat ARHGAP4 and Rac1-GTP from an unspecified species. 
    P98171 P01111 NRAS    HPRD  PubMed  
    BioGRID:106886 BioGRID:107208 FMNL1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106886 BioGRID:110378 MAP3K1    BioGRID  PubMed Two-hybrid 
    BioGRID:106886 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106886 BioGRID:113306 WHSC1    BioGRID  PubMed Affinity Capture-RNA 
    • 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 ...

    Markers

    Genotypes

    Potential readthrough

    Included gene: L1CAM

    Potential readthrough

    Included gene: NAA10

    Homology

    Clone Names

    • KIAA0131

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    Rho GTPase activator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    SH3/SH2 adaptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    Rho protein signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    		  
    apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    cytoskeleton organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    neurotrophin TRK receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of Rho GTPase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    focal adhesion IDA
    Inferred from Direct Assay
    more info
    		  
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		  
    Preferred Names
    rho GTPase-activating protein 4
    Names
    rho GTPase-activating protein 4
    Rho-GAP hematopoietic protein C1
    rho-type GTPase-activating protein 4

    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_013220.1 RefSeqGene

      Range
      5001..23885
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001164741.1 → NP_001158213.1  rho GTPase-activating protein 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI249937, BC052303, X78817
      Consensus CDS
      CCDS55540.1
      UniProtKB/Swiss-Prot
      P98171
      Related
      ENSP00000359045, OTTHUMP00000026003, ENST00000370028, OTTHUMT00000061117
      Conserved Domains (4) summary
      smart00324
      Location:558 – 731
      Blast Score: 488
      RhoGAP; GTPase-activator protein for Rho-like GTPases
      cl02570
      Location:543 – 730
      Blast Score: 739
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
      cl12013
      Location:52 – 321
      Blast Score: 608
      BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
      cd11956
      Location:788 – 842
      Blast Score: 293
      SH3_srGAP4; Src homology 3 domain of Slit-Robo GTPase Activating Protein 4

    2. NM_001666.4 → NP_001657.3  rho GTPase-activating protein 4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1. The resulting isoform (2) lacks an alternate segment, compared to isoform 1.
      Source sequence(s)
      AI249937, BC052303, D50921, X78817
      Consensus CDS
      CCDS14736.1
      UniProtKB/Swiss-Prot
      P98171
      Related
      ENSP00000203786, OTTHUMP00000026004, ENST00000350060, OTTHUMT00000061119
      Conserved Domains (4) summary
      cd07656
      Location:52 – 281
      Blast Score: 650
      F-BAR_srGAP; The F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of Slit-Robo GTPase Activating Proteins
      smart00324
      Location:518 – 691
      Blast Score: 485
      RhoGAP; GTPase-activator protein for Rho-like GTPases
      cl02570
      Location:503 – 690
      Blast Score: 735
      RhoGAP; RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when ...
      cd11956
      Location:748 – 802
      Blast Score: 295
      SH3_srGAP4; Src homology 3 domain of Slit-Robo GTPase Activating Protein 4

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 PATCHES

    Genomic

    1. NW_003871103.2 Reference GRCh37.p10 PATCHES

      Range
      1380500..1399384, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000023.10 Reference GRCh37.p10 Primary Assembly

      Range
      153172830..153191714, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      141824230..141844372, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018934.1 Alternate CHM1_1.0

      Range
      153040881..153059771, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01045337.1 (8868..12719) None
    genomic ABBA01045338.1 None
    genomic ABBA01045339.1 None
    genomic ABBA01045340.1 None
    genomic ABBA01045341.1 None
    genomic ABBA01045342.1 (3278..4245) None
    genomic AMYH01023303.1 (35513..54403) None
    genomic CH471172.2 EAW72777.1
      EAW72778.1
      EAW72779.1
      EAW72780.1
      EAW72781.1
      EAW72782.1
    genomic U52112.2 (60313..79197) None
    genomic Z68128.1 CAA92213.1
    mRNA AI249937.1 None
    mRNA AK294562.1 BAH11812.1
    mRNA AY183123.1 AAO66337.1
    mRNA BC023626.2 AAH23626.1
    mRNA BC052303.1 AAH52303.1
    mRNA D50921.1 BAA09480.1
    mRNA X78817.1 CAA55394.1
    other-genetic AM392626.1 CAL37504.1
    other-genetic AM393222.1 CAL38100.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P98171.2 GenPept UniProtKB/Swiss-Prot:P98171

    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
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
      • 3D structures
        3D structure of a gene
      • BioAssay
        Related PubChem BioAssays
      • BioProjects
        BioProjects related to a gene
      • BioSystems
        BioSystems
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • EST
        Link to related EST entry
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
      • Map Viewer
        These links are maintained by the Map Viewer group and are provided when a GeneID is annotated on a map for the same species.
      • Nucleotide
        Link to related Nucleotide entry
      • OMIM
        Links between OMIM and Gene are calculated by Gene based on MIM numbers included in the summary and phenotype sections of the Gene record.
      • Probe
        Related Probe entry
      • Protein
        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
      • SNP: Genotype
        Gene Genotype Report
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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