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FLASH GENE
Symbol ARHGEF18 contributors: mct - updated : 11-07-2023
HGNC name rho/rac guanine nucleotide exchange factor (GEF) 18
HGNC id 17090
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a Dbl homology domain
  • a pleckstrin (PH) homology domain Rho-GEF domain
    • HOMOLOGY
    Homologene
    FAMILY Rho GTPase GEF family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,tight
    plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    text
  • is a key component of tight junctions and adherens junctions
    • basic FUNCTION
  • A guanine nucleotide exchange factor for RhoA and Rac1 regulating cell shape and reactive oxygen species
  • regulates the activity of RHOA and RAC1, and GNB1, GNG2 subunits of heterotrimeric G proteins are activators of ARHGEF18 under physiological conditions
  • junction-associated protein that drives RHOA signalling at the junctional complex and regulates tight-junction assembly and epithelial morphogenesis
  • drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells
  • ARHGEF18-mediated activation of the small GTPase RHOA is required to maintain apicobasal polarity at the onset of retinal differentiation and to control the ratio of neurogenic to proliferative cell divisions
  • is a key regulator of tissue architecture and function, controlling apicobasal polarity and proliferation through RhoA activation
  • STK11 and ARHGEF18 control RHOA activity in the bronchial epithelial cells to promote apical junction assembly
  • is required to maintain apico-basal polarity, localization of tight junctions and cortical actin, thus shaping cellular morphology
  • governs cell motility and lumen formation during tubulogenesis through a ROCK-myosin-II pathway
  • guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions
  • implicated in maintenance of epithelial cell polarity
  • regulate horizontal axon branching of cortical upper layer neurons
  • ARHGEF18/p114RhoGEF is a tight junction-associated RHOA activator that forms complexes with myosin II, and regulates actomyosin contractility
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a junction-associated RHO signalling module that drives spatially restricted activation of RHOA to regulate junction formation and epithelial morphogenesis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activated RHOA and RAC1 but not CDC42 proteins
  • activated by G betagamma subunits
  • associates with a complex containing myosin II, ROCK2 and the junctional adaptor cingulin
  • EPB41L4B interacts with and activates ARHGEF18, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell-cell junctions
  • key regulator of RHOA-ROCK2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium
  • governs cell motility and lumen formation during tubulogenesis through a ROCK-myosin-II pathway
  • regulation of RHOA activation through ARHGEF18 is important for tissue morphogenesis and migration and in the assembly and maintenance of cell-cell junction
  • SEPTIN9 regulates RhoA signaling at the base of cilia by binding and activating the RhoA guanine nucleotide exchange factor, ARHGEF18
    • cell & other
    REGULATION
    activated by GNB1, GNG2 (GNB1, GNG2, but not Galpha subunits of heterotrimeric G proteins stimulated ARHGEF18-dependent SRE activity)
    ASSOCIATED DISORDERS
    corresponding disease(s) ARRP21
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mutations of the guanine nucleotide exchange factor ArhGEF18 affect apicobasal polarity of the retinal neuroepithelium in medaka fish