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FLASH GENE
Symbol RASA3 contributors: mct - updated : 27-02-2015
HGNC name RAS p21 protein activator 3
HGNC id 20331
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • BTK motif
  • PH domain
  • C2A and C2B domains are involved in membrane binding and calcium-dependent activation of some GAPs, and catalytic activity of RASA3 is located within the RasGAP domain
  • protein kinase C conserved region
    • HOMOLOGY
    interspecies homolog to murine Rasa3
    Homologene
    FAMILY GAP1 family of GTPase activating protein
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • constitutively bound to the membrane via interactions of its pleckstrin homology (PH) domain with PIP2 and PIP3
    • basic FUNCTION
  • stimulates the GTPase activity of normal RAS p21
  • suppressor of RAS function
  • role in intracellular calcium homeostasis
  • might be a specific IP4 receptor
  • critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis
  • RASA3 catalytic activity controls likely RBGEF1 activation and integrin signaling during megakaryocyte differentiation
  • function of RASA3 during megakaryopoiesis, megakaryocyte adhesion and migration as well as integrin signaling
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule other,
    binds inositol tetrakisphosphate with high affinity
    protein
  • links GNAI1 proteins to inhibit GNAQ-induced RAS/ERK1/2 activation
  • RASA3 targets RAS and RABGEF1
  • P2RY12 signaling is required to inhibit RASA3 and enable sustained RABGEF1-dependent platelet activation and thrombus formation at sites of vascular injury
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice, reduced expression of Rasa3 led to premature platelet activation and markedly reduced the life span of circulating platelets
  • Rasa3 catalytic inactivation in mouse hematopoietic cells results in a lethal syndrome characterized by severe defects during megakaryopoiesis, thrombocytopenia and a predisposition to develop preleukemia
  • scat phenotype is due to a mutation in Rasa3 with its mislocalization leading to its loss of function, and to crisis and remission episodes