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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000180 20 - 3.641 - 1103 - 1995 7777544

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Visual eye retina     specific Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial sensory visual outer nuclear layer specific Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Homo sapiens Visual rod 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
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed neurosensorial visual degenerative 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 neurosensorial visual degenerative 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 (