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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
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