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FLASH GENE
Symbol ARHGAP35 contributors: mct/npt/pgu - updated : 13-01-2015
HGNC name Rho GTPase activating protein 35
HGNC id 4591
Location 19q13.32      Physical location : -
Synonym name
  • Rho GAP p190A
  • glucocorticoid receptor repression factor 1
  • glucocorticoid receptor DNA binding factor 1
  • Synonym symbol(s) GRF-1, PI90A, KIAA1722, p190RhoGAP, MGC10745, GRLF1
    DNA
    TYPE functioning gene
    STRUCTURE 86.40 kb     6 Exon(s)    1 Copie(s)
    regulatory sequence Binding site
    text structure DNA binding site
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 8904 - 1499 - 2000 11054565
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveintestinelarge intestinecolon moderately
     stomach   moderately
    Lymphoid/Immunelymph node   predominantly
    Reproductivefemale systembreastmammary gland moderately
     female systemovary  moderately
    Respiratorylung   moderately
    Skin/Tegumentskin   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal GBDS1 region is necessary and sufficient for ARHGAP35 mitotic ubiquitination and degradation, and four N-terminal AAs are necessary for the degradation of ARHGAP35 in mitosis
  • three zinc finger structures
  • a leucine zipper motif containing one cystein
  • four FF domains
  • a Rho-GAP domain
  • conjugated PhosphoP
    mono polymer dimer
    HOMOLOGY
    interspecies homolog to rattus P190A
    ortholog to Drosophila RhoGAPp190
    Homologene
    FAMILY
  • nuclear receptor superfamily
  • CATEGORY regulatory , DNA associated , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    basic FUNCTION
  • repressing transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'- GAGAAAAGAAACTGGAGAAACTC-3'
  • may participate in the regulation of retinal development and degeneration
  • may transduce signals from p21-ras to the nucleus, acting via the ras GTP-ase activating protein (GAP)
  • may also act as a tumor suppressor
  • acting as a GTPase activator
  • regulating cadherins function
  • codependent role, with CTNND1, in regulating Rac-dependent antagonism of Rho
  • GTPase activating protein (GAP) specific for Rho, playing a role in cytokinesis
  • involved in co-regulation of Rho activity and ECT2 in the cleavage furrow determines whether cells properly complete cytokinesis
  • by linking RAC1 activation and RHOA inhibition, is critical to the protective effects of ANGPT1 against endotoxin
  • major target for ERK signaling in adhesion assembly with role for ERK phosphorylation of the C terminus in ARHGAP35 localization and activity
  • GTPase-activating protein known to regulate actin cytoskeleton dynamics by decreasing RhoGTP levels through activation of Rho intrinsic GTPase activity
  • reduction of ARHGAP35 is a critical mechanism by which increased RhoGTP levels are achieved in late mitosis, thereby ensuring proper cell division
  • GTPase-activating protein (GAP) known to regulate actin cytoskeleton dynamics by decreasing RhoGTP levels through activation of the intrinsic GTPase activity of RHO
  • CELLULAR PROCESS cell cycle, progression
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text
  • retinal development
  • negative regulation of progession through cell cycle
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
  • dimer p190A and p190B
  • part of PTK2-RASA1-GRLF1 complex that regulates polarity in migrating cells
  • INTERACTION
    DNA
  • binding to 5'- GAGAAAAGAAACTGGAGAAACTC-3
  • interacting with GCCR promoter (repressing GCCR expression)
  • RNA
    small molecule nucleotide,
  • GTP binding
  • protein
  • interacting with CTNND1
  • PTK6 substrate (phosphorylates GRLF1 at the Y(1105) residue, thereby promoting the association of GRLF1 with RASA1)
  • substrate of PTPRZ1, with GIT1, and MAGI1
  • RND1, RND2, RND3 bind directly to ARHGAP35 and equally induce activation of ARHGAP35 (pMID: 22357615)
  • RND1, RND2, and RND3 stability is acutely dependent on interaction with their effectors such as PLEKHG5 or ARHGAP35
  • interaction with C-terminal domain of CTNND1 modulates endothelial cytoskeleton and permeability
  • PLXNB2 competes with ARHGAP35 for binding to RND3, thus blocking the RND3-mediated inhibition of RHOA and also recruits RhoGEFs to directly stimulate RHOA activity
  • cell & other
    REGULATION
    activated by integrin signaling (through Arg activates GRLF1 by promoting its association with RASA1, resulting in recruitment of GRLF1 to the cell periphery where it inhibits RHOA, RHOB)
    Other regulated by the glucocorticoids
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in pancreatic carcinomas and gliomas
    tumoral   deletion    
    in pancreatic carcinomas and gliomas
    tumoral     --over  
    may be involved in the carcinogenesis of lung adenocarcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    possible molecular target for treatment of lung adenocarcinoma
    ANIMAL & CELL MODELS