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Symbol GUCY2D contributors: shn/npt/pgu - updated : 21-05-2012
HGNC name guanylate cyclase 2D, membrane (retina-specific)
HGNC id 4689
Corresponding disease
CORD5 retinal cone-rod dystrophy 5
CORD6 retinal cone-rod dystrophy 6
LCA1 Leber congenital amaurosis, type 1
Location 17p13.1      Physical location : 7.905.987 - 7.923.658
Synonym name
  • retinal guanylate cyclase-1
  • cone rod dystrophy 5/6
  • rod outer segment membrane guanylate cyclase
  • olfactory guanylyl cyclase GC-D
  • olfactory neuroepithelial guanylate cyclase
  • Synonym symbol(s) retGC, RETGC-1, ROS-GC1, CYGD, LCA1, LCA, CORD5, CORD6, GUC2D, GUC1A4, GC-E, GC-D, ONE-GC, GC1
    EC.number 4.6.1.2
    DNA
    TYPE functioning gene
    STRUCTURE 17.67 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    MAPPING cloned Y linked N status confirmed
    Map pter - D17S1353 - D17S1796 - GUCY2D - D17S1812 - D17S1805 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 3.641 - 1103 - 1995 7777544
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Visualeyeretina  specific Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsensoryvisualouter nuclear layerspecific Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Visualcone photoreceptor Homo sapiens
    Visualrod photoreceptor Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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
  • 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
  • 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 (