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FLASH GENE
Symbol ARHGEF6 contributors: mct - updated : 10-01-2017
HGNC name Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
HGNC id 685
Corresponding disease
MRX46 mental retardation, 46
Location Xq26.3      Physical location : 135.747.713 - 135.863.503
Synonym name
  • PAK-interacting exchange factor alpha
  • rho guanine nucleotide exchange factor 6
  • Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6
  • Rac/Cdc42 guanine exchange factor (GEF) 6
  • Synonym symbol(s) COOL2, COOL-2, ALPHAPIX, KIAA0006, ALPHA-PIX, PIXA
    DNA
    TYPE functioning gene
    STRUCTURE 116.11 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC392545 X similar to high mobility group protein homolog HMG4 LOC389887 X similar to RIKEN cDNA 1110012O05 CXX1 Xq26 CAAX box 1 DKFZP564B147 Xq26.3 DKFZP564B147 protein LOC159049 Xq26.3 hypothetical LOC159049 FLJ20527 Xq26.3 hypothetical protein FLJ20527 LOC392546 X similar to hypothetical protein FLJ20527 LOC389888 X similar to hypothetical protein FLJ20527 LOC389889 X hypothetical gene supported by BC061642 ZNF75 Xq26 zinc finger protein 75 (D8C6) FLJ23614 Xq26.3 hypothetical protein FLJ23614 LOC392547 X similar to KIAA0445 protein LOC203522 Xq26.3 hypothetical protein LOC203522 LOC392548 X similar to C-ets-2 protein LOC139587 Xq26.3 similar to sarcoma antigen; putative tumor antigen MGC27005 Xq26.3 hypothetical protein MGC27005 SAGE Xq28 hypothetical protein MGC27005 LOC93380 Xq26.3 hypothetical protein LOC93380 SLC9A6 Xq26.3 solute carrier family 9 (sodium/hydrogen exchanger), isoform 6 LOC392549 X similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) LOC139542 Xq26.3 similar to E2F transcription factor 6 isoform a FHL1 Xq26 four and a half LIM domains 1 FLJ12649 Xq26.3 hypothetical protein FLJ12649 GPR112 Xq26.3 G protein-coupled receptor 112 BRS3 Xq26-q28 bombesin-like receptor 3 HTATSF1 Xq26-Xq27 HIV TAT specific factor 1 VGLL1 Xq26.3 vestigial like 1 (Drosophila) TNFSF5 Xq26 tumor necrosis factor (ligand) superfamily, member 5 (hyper-IgM syndrome) ARHGEF6 Xq26 Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 LOC392550 X similar to ribosomal protein L7 LOC392551 X similar to Ras-related protein Rab-28 (Rab-26) RBMX Xq26 RNA binding motif protein, X chromosome LOC389890 X hypothetical gene supported by AF419855; NM_005839 LOC389891 X similar to ENSANGP00000013187 GPR101 Xq25-27.1 G protein-coupled receptor 101 LOC286472 Xq26.3 similar to Ras-related C3 botulinum toxin substrate homolog DJ20J23.1 ZIC3 Xq26.2 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila) LOC389892 X similar to Mothers against decapentaplegic homolog interacting protein (Madh-interacting protein) (Smad anchor for receptor activation) (Receptor activation anchor) (hSARA) (Novel serine protease) (NSP)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 5282 - 776 - 2015 26507661
    21 - 4820 - 622 - 2015 26507661
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
     thymus   highly
    Cardiovascularheart   highly
    Nervousbrain     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscular    
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal calponin homology domain,(unique to ARHGEF6)
  • a SH3 homology domain
  • a Dbl and a pleckstrin homology (PH) domains
  • HOMOLOGY
    interspecies homolog to rattus arhgef6
    Homologene
    FAMILY
  • cytoplasmic proteins family
  • CATEGORY regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,intermed filament
    text
  • lamellipodia
  • is localized to dendritic spines
  • basic FUNCTION
  • activator of Ras-like family of Rho proteins by exchanging bound GDP for GTP
  • putatively involved in axonal outgrowth,control of shape and size of dendrites
  • invoved in integrin-mediated signaling leading to activation of the GTPases RAC1 and/or CDC42
  • ARHGEF6 is localized in dendritic spines where it contributes to regulate spine morphogenesis probably by acting through a downstream activation of PAK3
  • ARHGEF6 and GIT2 are required for neuronal differentiation
  • RELN and the CDC42/RAC1 guanine nucleotide exchange factor ARHGEF6 promote dendritic Golgi translocation in hippocampal neurons
  • is a regulator of thymocyte migration and subsequent arrest that is linked to positive selection
  • recycling regulator ARHGEF6 and the degradation factor CBL closely cooperate in the regulation of EGFR trafficking
  • ARHGEF6 and ARHGEF7, respectively, are guanine nucleotide exchange factors (activators) for the Rho family small GTP-binding protein family members RAC1 and CDC42
  • CELLULAR PROCESS cell life, proliferation/growth
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PARVB (involved in reorganization of subsarcolemmal cytoskeletal actin by activation of RAC1 through ARHGEF6 and ARHGEF7 in skeletal muscle) (Matsuda 2008)
  • CBL negatively regulates ARHGEF6-mediated cell migration and invasion and the lack of CBL in the C6 and A172 glioma cells is respon
  • phosphorylated state of ARHGEF6 was required to activate first RAC1 and subsequently PYGM
  • interacts with the E3 ubiquitin ligase CBL, an enzyme that attaches ubiquitin to EGFR, thereby labelling this tyrosine kinase receptor for lysosomal degradation
  • function of ARHGEF6 as a strong promoter of EGFR recycling
  • ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex
  • cell & other
    REGULATION
    Phosphorylated by PRKCQ (to activate RAC1 and consequently PYGM, PRKCQ phosphorylates ARHGEF6 in T cells)
    ASSOCIATED DISORDERS
    corresponding disease(s) MRX46
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    deleted in gastric carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • imbalance in activity of different Rho GTPases may underlie altered neuronal connectivity and impaired synaptic function and cognition in Arhgef6 knockout mice