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FLASH GENE
Symbol ARHGEF11 contributors: mct/pgu - updated : 22-06-2018
HGNC name Rho guanine nucleotide exchange factor (GEF) 11
HGNC id 14580
Location 1q23.1      Physical location : 156.904.632 - 157.015.162
Synonym name
  • glutamate transporter EAAT4 associated protein 48
  • RhoGEF glutamate transport modulator
  • glutamate transporter EAAT4-associated protein 48
  • Similar to Mouse Lsc oncogene
  • Synonym symbol(s) KIAA0380, GTRAP48, PDZ-RHOGEF
    DNA
    TYPE functioning gene
    STRUCTURE 110.53 kb     40 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D1S2624 - D1S506 - ARHGEF11 - D1s3139 - D1S1653 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    40 - 6784 168 1522 - 2007 17287471
    41 - 6904 - 1562 - 2007 17287471
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Nervousbrain   highly
     nerve   highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal tandem DH/PH (Dbl homology/pleckstrin homology) domain
  • PDZ (PSD95/disc large/ZO1) domain
  • two proline rich sequence
  • a regulator of G protein signaling (RGS) homology domain
  • HOMOLOGY
    interspecies homolog to murine LSC oncogene
    Homologene
    FAMILY RGS-RhoGEF family
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • translocated to the plasma membrane after stimulation
  • in the early phases of cell-cell contact, ARHGEF11 was located at primordial adherens junctions
  • basic FUNCTION
  • specific guanine nucleotide exchange factor for RhoA, not for RAC1 or CDC42
  • involved in neurite retraction through Rho dependent signaling
  • playing a role in SEMA4D-plexin-B1 mediating signal transduction
  • supposed to influence insulin signaling
  • involved in G protein signaling and is a pathway known to play a role in both insulin secretion and action
  • guanine nucleotide exchange factor (GEF) for RHOA, mediating RHOA-dependent responses and determines their spatial distribution
  • mediates RHOA-myosin light chain signaling pathways at cell-cell junctions, functioning in cooperation with TJP1, to regulate the paracellular barrier and the organization of the apical junctional complex and perijunctional actomyosin ring of epithelial cells
  • mediates TJP1-dependent junction assembly and barrier formation in mammary epithelial cells
  • generally regulates apical junctions and junction-associated actomyosin in various epithelial tissues
  • acts as a key determinant of mammalian metabolism and obesity-associated pathologies
  • is a specific guanine nucleotide exchange factors (GEF) for RHOA, which is a critical regulator of actin cytoskeleton dynamics and organization of dendritic spines and inhibitor of spine maintenance
  • is likely to be associated with synaptic membranes and regulation of spine
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • PTK2B/ARHGEF11 couples RHOA activation to Ca(2+)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • links PTK2B to RHOA
  • interacting with plexin B1(PLXNB1) through PDZ domain
  • with PTK2 and ROCK2, cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts
  • targeting ARHGEF11 to KLHL20 required ARHGEF11 phosphorylation by MAPK14 mitogen-activated protein kinase
  • associates with tight junctions (TJs) by binding to TJP1, in polarized epithelial cells
  • mesenchymal ARHGEF11 transcripts contain a C-terminal exon that binds to PAK4 and inhibits RhoA activation by ARHGEF11
  • ablation of ESRP1 and ESRP2 impairs epithelial tight junction (TJ) integrity through loss of the epithelial isoform of Rho GTP exchange factor ARHGEF11
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to type 2 diabetes (T2D) and impaired glucose tolerance (IGT)
    Variant & Polymorphism SNP
  • R1467H assoociated with increased risk of T2D or T2D/IGT
  • SNP rs6427340 (intron 2), in which the less common allele was the risk allele for type 2 diabetes
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS