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FLASH GENE
Symbol GUCY2D contributors: shn/npt/pgu - updated : 21-05-2015
HGNC name guanylate cyclase 2D, membrane (retina-specific)
HGNC id 4689
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • N terminal signal peptide
  • a extracellular domain
  • a transmembrane domaine
  • kinase domain
  • a dimerization domain
  • a C terminal catalytic domain
    • mono polymer dimer
    HOMOLOGY
    interspecies ortholog to Gucy2d, Mus musculus
    ortholog to Gucy2d, Rattus norvegicus
    ortholog to GUCY2D, Pan troglodytes
    Homologene
    FAMILY
  • adenylyl cyclase class-4/guanylyl cyclase family
    • CATEGORY enzyme , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • presence of GUCY2D, GUCA1A, and PDE2A predominant in the cilia, yet to a lesser degree, they are also present in other regions of the olfactory neurons
  • localized exclusively to the cellular membranes, the plasma membrane, and the endoplasmic reticulum (ER), not in nucleus
    • basic FUNCTION
  • plays a key role in the phototransduction cascade by controlling intracellular calcium concentration via the influence on cation channels of its enzymatic product, guanosine 3', 5'-cyclic monophosphate (cGMP)
  • involved in phosphotransduction, especially in the recovery of the dark state often the excitation process of photoreceptor by light stimulation
  • involved in retinal synaptic activity
  • Ca(2+) bimodal signal transduction switch
  • may participate in transport of peripheral membrane proteins from the endoplasmic reticulum (ER) to the outer segments
  • transducer of three odorants: green pepper, uroguanylin , and atmospheric CO2
  • plays a crucial role in phototransduction by catalyzing the synthesis of cGMP in rod and cone photoreceptors
  • both native GUCY2D, and GUCY2F isozymes are important for cGMP synthesis in photoreceptors
  • GUCY2D and GUCA1A are critical for a precisely controlled synthesis of the second messenger cGMP
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS phototransduction
    text involved in the resynthesis of cGMP required for recovery of the dark state after phototransduction
  • Reaction catalysed: GTP <=> 3',5'-cyclic GMP + diphosphate
    • PATHWAY
    metabolism purine/pyrimidine
    signaling sensory transduction/vision
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • guanylyl cyclase activating protein-2, GCAP2 (
  • GC-activating proteins, GCAPs (
  • GUCA1A, through its fragment of amino acids 836&
    • 8722;1103
  • RD36 colocalizes and binds to GUCY2D and GUCY2F and plays a crucial role in their stable expression and membrane trafficking in rod and cone photoreceptors
  • GUCA1A is the 'first-response' sensor protein that stimulates GUCY2D early in the response and thus limits the SPR amplitude
  • GUCY2D, GUCY2F interaction with RD3 inhibits GC catalytic activity and promotes the exit of GUCY2D, GUCY2F from the endoplasmic reticulum and their trafficking to photoreceptor outer segments
  • RD3 is essential for normal expression of retinal membrane guanylyl cyclase (GUCY2D) in photoreceptor cells, and blocks GUCY2D catalytic activity and stimulation by guanylyl cyclase-activating proteins (GCAPs)
    • cell & other
    REGULATION
    activated by nanomolar concentrations of Ca2 by Ca2+ binding proteins
    GUCA1A
    induced by GUCA1A, after substitution of Ca(2+) by Mg(2+) in its EF-hands, GUCA1A stimulates photoreceptor guanylyl cyclase, GUCY2D, in response to light
    inhibited by calcium
    RGS9-1 (
    RD3 (inhibition of GUCY2D by RD3 may be utilized by photoreceptors to block GUCY2D activity during its maturation and/or incorporation into the photoreceptor outer segment rather than participate in dynamic regulation of the cyclase by Ca(2+) and GCAPs)
    ASSOCIATED DISORDERS
    corresponding disease(s) LCA1 , CORD6 , CORD5
    related resource Retinal Information Network
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional somatic mutation     loss of function
    complete lose of function of RetGC1 (GUCY2D) in LCA
    constitutional somatic mutation   --over gain of function
    CORD6 mutations result in failure to inactivate cyclase activity at high physiological Ca2+ concentrations. RetGC1 is constituvely activated by its activators GCAP1 and GCAP2
    constitutional germinal mutation      
    in LCA2 (acting as a gene modifier)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualdegenerative
    delivery of AAV5 vectors containing murine guanylate cyclase-1 (GC1) cDNA is capable of restoring cone-mediated function and visual behavior and preserving cone photoreceptors in the GC1 knockout (GC1KO) mouse for 3 months
    neurosensorialvisualdegenerative
    AAV8(Y733F) is the most efficient vector for Cone function restauratioon in guanylate cyclase-1 knockout (GC1KO) mouse which is preserved for at least 11 months after treatment
    ANIMAL & CELL MODELS
    Gucy2d KO mice develop a cone dystrophy.
  • A 22-kb deletion in the chicken GUCY2D orthologue, GUCY1B leads to a retinal dystrophy in the central retina and proceeds progressively towards the periphery
  • blindness associated with loss of function of retGC1 in the GUCY1*B avian model of LCA1 can be reversed using viral vector-mediated gene transfer (
  • Gucy2f knockdown Zebrafish display significantly lower vision and loss and shortening of cone and rod outer segments leading to early visual dysfunction and photoreceptor layer dystrophy (