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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
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