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FLASH GENE
Symbol ARAP1 contributors: mct/ - updated : 10-03-2014
HGNC name ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1
HGNC id 16925
Location 11q13.4      Physical location : 72.396.114 - 72.463.434
Synonym name
  • Arf-GAP, Rho-GAP, ankyrin repeat and pleckstrin homology domain-containing protein 2
  • centaurin, delta 2
  • ARAP1b protein
  • Synonym symbol(s) KIAA0782, Cnt-d2, CENTD2
    DNA
    TYPE functioning gene
    STRUCTURE 67.32 kb     33 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    33 - 4966 137 1205 - 2010 20554524
    also called CENTD2 variant 1/isoform a
    30 - 4802 137.8 1210 - 2008 18165900
    35 - 5155 162.2 1450 - 2010 20554524
    31 - 4750 - - - 2010 20554524
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Mus musculus
     vesselaorta  highly Mus musculus
    Digestivestomach   highly
    Endocrineadrenal gland   highly Mus musculus
     pancreas     Homo sapiens
    Lymphoid/Immunetonsils   highly
    Urinarykidney   predominantly Mus musculus
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Urinarymesangial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two tandem PH domains are immediately N-terminal of the Arf GAP domain, and one of these fits the consensus sequence for PtdIns(3,4,5)P(3) binding
  • an ARF-GAP domain
  • a RHO-GAP domain lacking the predicted catalytic origine
  • a sterile alpha motif (SAM)
  • five PH domains that regulates endocytic trafficking of the epidermal growth factor receptor (EGFR)
  • HOMOLOGY
    intraspecies paralog to CENTD1
    Homologene
    FAMILY
  • centaurin family
  • CATEGORY adaptor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • is located near both the Golgi and the plasma membrane in other cell types as beta cells
  • basic FUNCTION
  • PIP3 dependent GAP that regulates Arf, Rho and Cdc42 dependent cell activities
  • likely involved in the regulation of the cell-specific trafficking of TNFRSF10A and might thus affect the efficacy of TRAIL-induced apoptosis
  • regulator of small GTPases with both an Arf GAP and a Rho GAP domain
  • regulates the endocytic traffic of EGFR and, consequently, the rate of EGFR signal attenuation
  • controls the late steps of the endocytic trafficking of the EGFR
  • phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3))-dependent Arf GTPase-activating protein
  • regulates the ring size of circular dorsal ruffles through ARF1 and ARF5
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner, inhibiting down-regulation of EGF receptor through phosphorylation of ARAP1
  • rapidly and transiently associated with the edge of the cell and punctate structures containing RAB5, rabaptin 5 and EGFR but not early embryonic antigen 1 (EEA1)
  • activates ARF and RHO GTPases, which regulate membrane trafficking and actin cytoskeleton reorganization
  • possible regulatory interaction between the small GTPase regulator ARAP1 and LRRK1, which carries a small GTPase domain
  • interaction with SH3KBP1 regulates endocytic trafficking of the EGFR and affects ubiquitination of EGFR
  • may serve as a local modulator of vascular AGTR1 function
  • cell & other
  • targeted by phosphatidyl inositol (3,4,3) triphosphate
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    is associated with increased risk of T2D
    Susceptibility to type 2 diabetes (T2D)
    Variant & Polymorphism SNP
  • T2D-risk allele (C) of rs11603334 is associated with increased ARAP1 transcript levels in primary human pancreatic islets, disrupts binding of a protein complex containing transcriptional regulators, and increases transcriptional activity at the ARAP1 P1 promoter
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    ARAP1 antagonists might hold important therapeutic potential
    ANIMAL & CELL MODELS