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FLASH GENE
Symbol ARHGEF12 contributors: mct/pgu - updated : 08-07-2013
HGNC name Rho guanine nucleotide exchange factor (GEF) 12
HGNC id 14193
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • from N terminal,a PDZ (PSD/dics large/ZO1) domain
  • a LSC homology domain (LH)
  • a bipartite nuclear localization signal (NLS)
  • a DBL homology domain and a pleckstrin homology (PH) domain
  • HOMOLOGY
    interspecies homolog to murine Arhgef12 (89.4pc)
    homolog to rattus Arhgef12 (88.8pc)
    Homologene
    FAMILY
  • GEF family
  • CATEGORY regulatory , tumor suppressor , signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text
  • during cytokinesis, is condensed in the midbody, where it colocalizes with RHOA
  • basic FUNCTION
  • stimulating Rho-dependent signaling pathway
  • playing a role in SEMA4D-plexin-B1 mediating signal transduction
  • role for the exchange factors ARHGEF1 and ARHGEF12 in linking fibronectin signals to downstream RhoA activation
  • acting as a guanine nucleotide exchange factor for RhoA GTPase and may act as a GTPase-activating protein for GNA12, GNA13
  • candidate tumor suppressor gene
  • is a novel and temporally distinct RhoGEF required for completion of abscission
  • with ARHGEF10, ARHGEF2, ARHGEF12, PLEKHG1 and ARHGEF28, are involved in cyclic-stretch-induced perpendicular reorientation of endothelial cells
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • homo or hetero-oligomerizing with PDZ-RhoGEF
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding PLXNB1 cytoplasmic tail through the PDZ domain, PLXNB2, RHOA
  • interacting with GNA12 and GNA13
  • interacting with IGF1R
  • displayed GTPase activating protein (GAP) activity towards MAP3K7and, upon overexpression, impaired cell scattering, invasion and adhesion to fibronectin in response to HGF
  • associating with UNC5B to transduce the RhoA signal
  • is a new substrate of CYLD, providing novel insights into the regulation of RHOA activation
  • cell & other
    REGULATION
    activated by interaction with GNA13
    Other phosphorylated upon DNA damage probably by ATM or ATR
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    frequently underexpressed in breast and colorectal carcinomas
    tumoral fusion      
    with HRX (5' HRX-LARG) in acute myeloid leukemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS