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    ARHGEF5 Rho guanine nucleotide exchange factor 5 [ Homo sapiens (human) ]

    Gene ID: 7984, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ARHGEF5provided by HGNC
    Official Full Name
    Rho guanine nucleotide exchange factor 5provided by HGNC
    Primary source
    HGNC:HGNC:13209
    See related
    Ensembl:ENSG00000050327 MIM:600888; AllianceGenome:HGNC:13209
    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
    P60; TIM; GEF5; TIM1
    Summary
    Rho GTPases play a fundamental role in numerous cellular processes initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein may be involved in the control of cytoskeletal organization. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in thyroid (RPKM 23.4), skin (RPKM 15.6) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ARHGEF5 in Genome Data Viewer
    Location:
    7q35
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (144355402..144380632)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (145535577..145560799)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (144052495..144077725)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene ARHGEF35 antisense RNA 1 Neighboring gene OR2A1 antisense RNA 1 Neighboring gene olfactory receptor family 2 subfamily A member 9 pseudogene Neighboring gene olfactory receptor family 2 subfamily A member 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr7:144039739-144040663 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:144050275-144050774 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:144062707-144063275 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:144075440-144076639 Neighboring gene MPRA-validated peak6811 silencer Neighboring gene uncharacterized LOC124901817 Neighboring gene NOBOX oogenesis homeobox

    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 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. Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection. Liang Z, et al. Viruses, 2023 Jul 21. PMID 37515282, Free PMC Article
    2. Assignment of the human TIM proto-oncogene to 7q33-->q35. Takai S, et al. Cancer Genet Cytogenet, 1995 Aug. PMID 7656213
    3. Regulation of tolerance in the respiratory tract: TIM-1, hygiene, and the environment. Umetsu DT, et al. Ann N Y Acad Sci, 2004 Dec. PMID 15681748
    4. The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers. He P, et al. Biochimie, 2015 Apr. PMID 25645980
    5. Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer. Huang O, et al. Amino Acids, 2015 Jun. PMID 25743165

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection.
      Title: Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection.
    2. Tim protein and DDX11 physically and functionally interact and act in concert to preserve replication fork progression in perturbed conditions.
      Title: Tim/Timeless, a member of the replication fork protection complex, operates with the Warsaw breakage syndrome DNA helicase DDX11 in the same fork recovery pathway.
    3. Data indicate that Rho guanine nucleotide exchange factor 5 (ARHGEF5) is expressed in most human lung adenocarcinoma tissues and cell lines.
      Title: Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation.
    4. Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer.
      Title: Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer.
    5. The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.
      Title: The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.
    6. In conclusion, ARHGEF5/Src can be considered as a prognostic biomarker and a therapeutic target for patients with resected NSCLC.
      Title: Co-expression of Rho guanine nucleotide exchange factor 5 and Src associates with poor prognosis of patients with resected non-small cell lung cancer.
    7. A receiver operating characteristic curve constructed with HSP105 and TIM gave a sensitivity of 54.3% and 95% (38/40) specificity in discriminating esophageal squamous cell carcinoma from matched controls.
      Title: Identification of tumor antigens that elicit a humoral immune response in the sera of Chinese esophageal squamous cell carcinoma patients by modified serological proteome analysis.
    8. This study performed whole exome sequencing demonistrated that the true de novo variants represent mutations in genes (KCNH5, CLCN4, and ARHGEF15) not previously associated with epilepsies in humans.
      Title: Exome sequencing reveals new causal mutations in children with epileptic encephalopathies.
    9. Tim-Tipin complex might play a role in coupling DNA unwinding and DNA synthesis by directly affecting the catalytic activities of replication fork proteins.
      Title: Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.
    10. Overexpression of Arhgef5 promoted actin stress fiber remodeling through activating RhoA, and the activation of RhoA or Cdc42 was required for Src-induced podosome formation.
      Title: The guanine nucleotide exchange factor Arhgef5 plays crucial roles in Src-induced podosome formation.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
    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

    • DKFZp686N1969

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    enables lipid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in actin cytoskeleton organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in hematopoietic stem cell homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in myeloid dendritic cell chemotaxis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of DNA-binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of JUN kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of podosome assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of protein import IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of stress fiber assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    NOT involved_in regulation of ERK1 and ERK2 cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within regulation of GTPase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of actin cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of actin cytoskeleton organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cytoskeleton organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in anchoring junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell periphery IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cell projection IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		  
    located_in podosome IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    rho guanine nucleotide exchange factor 5
    Names
    Rho guanine nucleotide exchange factor (GEF) 5
    ephexin-3
    ephexin3
    guanine nucleotide regulatory protein TIM
    oncogene TIM
    p60 TIM
    transforming immortalized mammary oncogene

    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.

    mRNA and Protein(s)

    1. NM_005435.4 → NP_005426.2  rho guanine nucleotide exchange factor 5

      See identical proteins and their annotated locations for NP_005426.2

      Status: REVIEWED

      Source sequence(s)
      AK123596, AK160365, BC010046, BF209445, BI256663, CD674013
      Consensus CDS
      CCDS34771.1
      UniProtKB/Swiss-Prot
      A6NNJ2, Q12774, Q6ZML7
      UniProtKB/TrEMBL
      B9EGR7
      Related
      ENSP00000056217.5, ENST00000056217.10
      Conserved Domains (5) summary
      cd11940
      Location:1514 → 1568
      SH3_ARHGEF5_19; Src homology 3 domain of the Rho guanine nucleotide exchange factors ARHGEF5 and ARHGEF19
      cd01221
      Location:1378 → 1504
      PH_ephexin; Ephexin Pleckstrin homology (PH) domain
      pfam00169
      Location:1391 → 1497
      PH; PH domain
      pfam00621
      Location:1178 → 1356
      RhoGEF; RhoGEF domain
      pfam15441
      Location:1 → 478
      ARHGEF5_35; Rho guanine nucleotide exchange factor 5/35

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      144355402..144380632
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017012623.3 → XP_016868112.1  rho guanine nucleotide exchange factor 5 isoform X1

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654715.1 Reference GRCh38.p14 PATCHES

      Range
      404891..430104
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      145535577..145560799
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054359021.1 → XP_054214996.1  rho guanine nucleotide exchange factor 5 isoform X2

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001002861.1: Suppressed sequence

      Description
      NM_001002861.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q12774.3 GenPept UniProtKB/Swiss-Prot:Q12774

    Gene LinkOut

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

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