GUCA1A guanylate cyclase activator 1A (retina) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: GUCA1Aprovided by HGNC
Official Full Name: guanylate cyclase activator 1A (retina)provided by HGNC
Primary source: HGNC:4678
Locus tag: RP1-139D8.2
See related: Ensembl:ENSG00000048545; HPRD:02648; MIM:600364; Vega:OTTHUMG00000014696
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: COD3; GCAP; GUCA; GCAP1; GUCA1; CORD14; C6orf131; dJ139D8.6
Summary: This gene plays a role in the recovery of retinal photoreceptors from photobleaching. In the recovery phase, the phototransduction messeneger cGMP is replenished by retinal guanylyl cyclase-1 (GC1). GC1 is activated by decreasing Ca(2+) concentrations following photobleaching. The protein encoded by this gene, guanylyl cyclase activating protein 1 (GCAP1), mediates the sensitivity of GC1 to Ca(2+) concentrations. GCAP1 promotes activity of GC1 at low Ca(2+) concentrations and inhibits GC1 activity at high Ca(2+) concentrations. Mutations in this gene cause autosomal dominant cone dystrophy (COD3); a disease characterized by reduced visual acuity associated with progressive loss of color vision. Mutations in this gene prohibit the inactivation of RetGC1 at high Ca(2+) concentrations; causing the constitutive activation of RetGC1 and, presumably, increased cell death. This gene is expressed in retina and spermatagonia. [provided by RefSeq, Feb 2009]

Genomic context

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Location :: 6p21.1

Sequence :: Chromosome: 6; NC_000006.11 (42123144..42147794)

See GUCA1A in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Stimulation by GCAP increases the maximal velocity (Vmax) for retinal guanylyl cyclase activation up to 100-fold in HEK293 cell membranes.
Title: Retinal degeneration 3 (RD3) protein inhibits catalytic activity of retinal membrane guanylyl cyclase (RetGC) and its stimulation by activating proteins.
The consequences of specific mutations on GCAP1 structure and GC stimulation, are described.
Title: GCAP1 mutations associated with autosomal dominant cone dystrophy.
Observational study of genetic testing. (HuGE Navigator)
Title: Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.
all novel mutants of GCAP1 were able to act as a Ca2+-sensor protein, they differed in their Ca2+-dependent activation profiles leading to a persistent stimulation of guanylate cyclase activities at physiological intracellular Ca2+ concentration
Title: Mutations in the GUCA1A gene involved in hereditary cone dystrophies impair calcium-mediated regulation of guanylate cyclase.
metal binding in EF-hand 2 is crucial for GCAP1 attachment to RetGC1, and in EF-hand 3 it is less critical, although it enhances the efficiency of the GCAP1 docking on the target enzyme
Title: Binding of guanylyl cyclase activating protein 1 (GCAP1) to retinal guanylyl cyclase (RetGC1). The role of individual EF-hands.
Observational study of genotype prevalence and gene-disease association. (HuGE Navigator)
Title: A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration.
A novel GCAP1 mutation, I143NT, caused a form of autosomal dominant cone degeneration that destroys foveal cones by mid-life but spares some cones in the peripheral retina up to 75 years.
Title: A novel mutation (I143NT) in guanylate cyclase-activating protein 1 (GCAP1) associated with autosomal dominant cone degeneration.
A novel L151F mutation in the EF4 hand domain of GCAP1 is associated with autosomal dominant cone-rod dystrophy (adCORD).
Title: A novel GCAP1 missense mutation (L151F) in a large family with autosomal dominant cone-rod dystrophy (adCORD).
A novel L151F missense mutation in the EF4 high affinity Ca2+ binding site of GCAP1 is linked to adCD (autosomal dominant cone dystrophy) in a large pedigree.
Title: Autosomal dominant cone dystrophy caused by a novel mutation in the GCAP1 gene (GUCA1A).
This is the first report of this mutation also causing both cone-rod dystrophy and isolated macular dysfunction.
Title: Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy.

Submit: New GeneRIF Correction See all (12)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
P43080	Q02846	GUCY2D		HPRD	PubMed

Pathways from BioSystems

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Olfactory transduction, organism-specific biosystem (from KEGG)
Olfactory transduction, organism-specific biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
Olfactory transduction, conserved biosystem (from KEGG)
Olfactory transduction, conserved biosystemWithin the compact cilia of the olfactory receptor neurons (ORNs) a cascade of enzymatic activity transduces the binding of an odorant molecule to a receptor into an electrical signal that can be tra...
Phototransduction, organism-specific biosystem (from KEGG)
Phototransduction, organism-specific biosystemPhototransduction is a biochemical process by which the photoreceptor cells generate electrical signals in response to captured photons. The vertebrate cascade starts with the absorption of photons b...
Phototransduction, conserved biosystem (from KEGG)
Phototransduction, conserved biosystemPhototransduction is a biochemical process by which the photoreceptor cells generate electrical signals in response to captured photons. The vertebrate cascade starts with the absorption of photons b...
Visual signal transduction: Cones, organism-specific biosystem (from Pathway Interaction Database)
Visual signal transduction: Cones, organism-specific biosystem
Visual signal transduction: Cones
Visual signal transduction: Rods, organism-specific biosystem (from Pathway Interaction Database)
Visual signal transduction: Rods, organism-specific biosystem
Visual signal transduction: Rods

General gene information

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Markers

RH67862 (e-PCR)
- UniSTS:32822

RH47569 (e-PCR)
- UniSTS:72284

WI-9373 (e-PCR)
- UniSTS:39110

Genotypes

See GUCA1A SNP Geneview Report
See GUCA1A SNP Genotype Report
See GUCA1A SNP Variation Viewer Report

Homology

Homologs of the GUCA1A gene: The GUCA1A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
calcium sensitive guanylate cyclase activator activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
phototransduction	IEA Inferred from Electronic Annotation more info
signal transduction	NAS Non-traceable Author Statement more info	PubMed
visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: guanylyl cyclase-activating protein 1

Names: guanylyl cyclase-activating protein 1; GCAP 1; cone dystrophy 3; guanylin 1, retina; guanylate cyclase-activating protein, photoreceptor 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009938.1 RefSeqGene

Range

5001..29651

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000409.3 → NP_000400.2 guanylyl cyclase-activating protein 1

Status: REVIEWED

Source sequence(s)

BC031663, DB049592

Consensus CDS

CCDS4864.1

UniProtKB/Swiss-Prot

P43080

Related

ENSP00000053469, OTTHUMP00000196468, ENST00000053469, OTTHUMT00000040546

Conserved Domains (3) summary

cd00051
Location:91 – 161
Blast Score: 139

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

pfam13499
Location:97 – 160
Blast Score: 114

EF_hand_5; EF-hand domain pair

pfam13833
Location:30 – 80
Blast Score: 88

EF_hand_6; EF-hand domain pair

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p10 Primary Assembly

Range

42123144..42147794

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

41841195..41865841

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018917.1 Alternate CHM1_1.0

Range

42033516..42058157

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01050734.1 (3490..28136)	None
genomic	AL096814.26 (120159..144809)	None
genomic	AMYH01016302.1 (90399..115040)	None
genomic	CH471081.1	EAX04084.1
genomic	L36861.1	AAA60542.1
mRNA	AK125780.1	BAG54246.1
mRNA	AK313865.1	BAG36593.1
mRNA	BC031663.1	AAH31663.1
mRNA	DB049592.1	None
mRNA	L36859.1	AAA60541.1
other-genetic	DQ891302.2	ABM82228.1
other-genetic	DQ894487.2	ABM85413.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P43080.3	GenPept	UniProtKB/Swiss-Prot:P43080

Additional links

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Additional Links

Epigenomics
MIM 600364
Retina International Mutations of the Retinal Guanylate Cyclase Gene and the Retinal Guanylate Cyclase-activating Protein Gene gcmut.htm
UCSC UCSC
UniGene Hs.92858