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FLASH GENE
Symbol ARHGEF5 contributors: mct - updated : 21-05-2015
HGNC name Rho guanine nucleotide exchange factor (GEF) 5
HGNC id 13209
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a pleckstrin homology (PH) domain, required for podosome formation
  • a SH3 domain
  • GDP-GTP exchange with the DBL homology motif, interacting with N-terminal helices to exclude and prevent activation of Rho GTPases
    • HOMOLOGY
    intraspecies homolog to GDP-GTP exchange factor MLF2 and NGEF
    Homologene
    FAMILY
  • Dbl family of guanine nucleotide exchange factor for Rho GTPases
    • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION
    basic FUNCTION
  • may be playing an important role in proliferative breast disease
  • may be involved in the control of cytoskeletal organization
  • acts as an upstream regulator for the RHOA/ROCK-mediated cellular functions
  • is important not only for replication fork protection and checkpoint response, but also for replication
  • important factor in chemotaxis of a macrophage phage-like
  • is crucial for SRC-induced podosome formation
  • SRC SH3-binding protein, tyrosine-phosphorylated by SRC and bound to SRC to positively regulate its activity
  • acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with MCM2, MCM3, MCM4, MCM5, MCM6, MCM7 (Numata 2010)
  • can strongly activate RHOA and RHOB and weakly RHOC and RHOG, but not RAC1, RHOQ, RHOD
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer cell lines
    constitutional       loss of function
    attenuated allergic airway inflammation
    tumoral     --over  
    significantly increased in lung adenocarcinoma tissues and cell lines
    constitutional     --over  
    promoted actin stress fiber remodeling through activating RHOA, and the activation of RHOA or CDC42 was required for SRC-induced podosome formation
    Susceptibility
    Variant & Polymorphism other five alternative variants predominantly expressed in aggressive primary breast cancer
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS