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FLASH GENE
Symbol ASIC3 contributors: mct/npt - updated : 04-09-2015
HGNC name acid sensing (proton gated) ion channel 3
HGNC id 101
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • intracellular N and C termini
  • two hydrophobic transmembrane segments (TM2)
  • a large extracellular loop including several cysteine residues with conserved spacing
  • HOMOLOGY
    Homologene
    FAMILY
  • amiloride-sensitive sodium channels superfamily
  • degenerin/epithelial sodium channel (DEG/ENaC) superfamily
  • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text colocalizing with ACCN1 (ASIC2A)
    basic FUNCTION
  • proton gated cation channel subunit modulatory subunit of ACCN1 (ASIC2A)
  • involved in modulating moderate- to high-intensity pain sensation
  • may play an important role in the detection of lasting pH changes
  • might play a role in the neuronal response to noxious acidosis in sensory and central pathways
  • ligand-gated cation channel activated by extracellular protons, and is associated with an exercise-induced pressor reflex and possibly autonomic imbalance
  • ASIC3-containing neurons have a wide variety of sensory modalities in the vagal and glossopharyngeal sensory ganglia
  • may be involved in blood pressure regulation
  • thus, peripherally located ASIC1 and ASIC3 play different roles in the development of hyperalgesia after muscle inflammation
  • contribution of ASIC3 to established hypersensitivity associated with inflammation suggests that this channel may be an effective analgesic target for inflammatory pain states
  • particularly important sensor of nonadaptive pain associated with tissue acidosis
  • ASIC3A, ASIC3B, or ASIC3C are able to directly sense extracellular pH changes not only during acidification (up to pH 5.0), but also during alkalization (up to pH 8.0)
  • can thus constitute a particularly efficient molecular sensor for alkalization and/or recovery from acidification in neurons and other cell types where it may be expressed
  • is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers
  • important role of ASIC3 channels in regulating inflammatory pain via coincident detection of extracellular protons and inflammatory mediators
  • important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli
  • activation of ASIC3 and TRPV1 as well as enhanced SCN10A activity are essential for the development of long-lasting hyperalgesia in acid-induced, chronic, widespread muscle pain
  • fatigue reduces pH in muscle that subsequently activates ASIC3 on macrophages to enhance hyperalgesia to muscle insult
  • involved in many aspects of nociception, both in peripheral and central neurons
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ACCN1
  • cell & other
    REGULATION
    activated by extracellular protons
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to blood pressure regulation variation
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates