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FLASH GENE
Symbol GUCA1A contributors: mct/npt - updated : 26-11-2020
HGNC name guanylate cyclase activator 1A (retina)
HGNC id 4678
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three Ca++ binding motifs,
  • four EF-hand binding the Ca++ (EF-hand 2 is crucial for attachment to RETGC1, but EF-hand 3 is less critical, although it enhances the efficiency of the GUCA1A docking on the target enzyme, metal binding in EF-hand 4 has no role in the primary attachment to the cyclase, and it only triggers the activator-to-inhibitor functional switch in GUCA1A) (Peshenko 2008)
    • HOMOLOGY
    interspecies homolog to murine Guca1a
    Homologene
    FAMILY
    CATEGORY signaling neurotransmitter
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • cone outer and inner segments, in disk membrane regions, and to a lesser extent rod inner and outer segments
  • presence in the scattered population of the olfactory sensory neurons, predominantly present in the cilia, the site of odorant
    • yet, in a smaller quantity, is present also in other regions of the olfactory neuron transduction
  • with PDE2A are coexpressed in the same population of the olfactory sensory neurons
    • basic FUNCTION
  • EF-hand Ca(2+)-binding protein, regulating photoreceptor membrane guanylyl cyclase GUCY2D in a Ca2+ sensitive manner, activating photoreceptor guanylyl cyclase (GUCY2D) in the absence of Ca(2+) and inhibiting GUCY2D in a Ca(2+)-sensitive manner
  • involved in the Ca2+-dependent negative feedback regulation of membrane bound guanylate cyclases in the retina (Kitiratschky 2009)
  • is a natural Ca2+ sensor component of GUCY2D
  • physiological Ca2+ sensor of the odorant-linked GUCY2D transduction system
  • GUCA1A and GUCA1B (or guanylyl cyclase-activating proteins [GCAPs]) have been identified as important mediators of the photoreceptor response to changes in intracellular Ca2+
  • is a neuronal calcium sensor protein that regulates the phototransduction cascade in vertebrates by switching between activator and inhibitor of the target guanylate cyclase (GC) in a Ca2+-dependent manner
  • GUCY2D and GUCA1A are critical for a precisely controlled synthesis of the second messenger cGMP
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
  • constitutive part of the odorant-linked GUCY2D transduction machinery
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+/Mg2+ sensors
  • Mg(2+) binding critical for setting the actual dynamic range of GUCY2D regulation by GUCA1A at physiological levels of free Ca(2+)
  • is responsive to Mg²&
    • 8314; only in its low [Ca²&
    8314;] state and Mg²&
    8314;
    protein
  • after substitution of Ca(2+) by Mg(2+) in its EF-hands, stimulates photoreceptor guanylyl cyclase, RetGC1, in response to light (Peshenko 2008)
  • binds to the fragment of AAs 836&
    • 8722;1103 of GUCY2D
  • both GUCA1A and GUCA1B stimulate GUCY2F equally well at saturation (
  • GUCA1A is the 'first-response' sensor protein that stimulates GUCY2D early in the response and thus limits the SPR amplitude
    • cell & other
    REGULATION
    activated by TH (Liu 2007)
    ASSOCIATED DISORDERS
    corresponding disease(s) CORD14
    related resource Retinal Information Network
    Susceptibility to retinitis pigmentosa
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS