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Protein

Guanylyl cyclase-activating protein 1

Gene

GUCA1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated (PubMed:19459154). This Ca2+-sensitive regulation of retinal guanylyl cyclase is a key event in recovery of the dark state of rod photoreceptors following light exposure.Curated1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi64 – 75121PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi100 – 111122PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi144 – 155123PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-2514859. Inactivation, recovery and regulation of the phototransduction cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanylyl cyclase-activating protein 1
Short name:
GCAP 1
Alternative name(s):
Guanylate cyclase activator 1A
Gene namesi
Name:GUCA1A
Synonyms:C6orf131, GCAP, GCAP1, GUCA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4678. GUCA1A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Cone dystrophy 3 (COD3)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant cone dystrophy. Cone dystrophies are retinal dystrophies characterized by progressive degeneration of the cone photoreceptors with preservation of rod function, as indicated by electroretinogram. However, some rod involvement may be present in some cone dystrophies, particularly at late stage. Affected individuals suffer from photophobia, loss of visual acuity, color vision and central visual field. Another sign is the absence of macular lesions for many years. Cone dystrophies are distinguished from the cone-rod dystrophies in which some loss of peripheral vision also occurs.
See also OMIM:602093
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501P → L in COD3; some subjects may present a moderately severe cone-rod dystrophy; causes a decrease in the number of bound calcium ions from 3 to 2, without changing the activity profile. 2 Publications
Corresponds to variant rs104893968 [ dbSNP | Ensembl ].
VAR_010648
Natural varianti89 – 891E → K in COD3; exhibits an about 6-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060802
Natural varianti99 – 991Y → C in COD3; type 1A; alters calcium ion sensitivity, leading to the constitutive stimulating activity of GC1 at high calcium ion concentration, where normal GUCA1A inhibits it. 3 Publications
Corresponds to variant rs104893967 [ dbSNP | Ensembl ].
VAR_001372
Natural varianti100 – 1001D → E in COD3; exhibits an about 28-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060803
Natural varianti143 – 1431I → NT in COD3. 1 Publication
VAR_060805
Natural varianti151 – 1511L → F in COD3. 3 Publications
Corresponds to variant rs121434631 [ dbSNP | Ensembl ].
VAR_060806
Natural varianti155 – 1551E → G in COD3; constitutive activation of GC1. 1 Publication
VAR_012987
Natural varianti159 – 1591G → V in COD3; exhibits an about 18-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060807

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiGUCA1A.
MIMi602093. phenotype.
Orphaneti1872. Cone rod dystrophy.
1871. Progressive cone dystrophy.
PharmGKBiPA29062.

Polymorphism and mutation databases

BioMutaiGUCA1A.
DMDMi46577585.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedSequence analysis
Chaini2 – 201200Guanylyl cyclase-activating protein 1PRO_0000073803Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei3 – 31Deamidated asparagineSequence analysis

Keywords - PTMi

Lipoprotein, Myristate

Proteomic databases

PaxDbiP43080.
PeptideAtlasiP43080.
PRIDEiP43080.

Expressioni

Tissue specificityi

Retina; cone outer and inner segments, in particular, in disk membrane regions, and to a lesser extent rod inner and outer segments.

Gene expression databases

BgeeiENSG00000048545.
CleanExiHS_GUCA1A.
ExpressionAtlasiP43080. baseline and differential.
GenevisibleiP43080. HS.

Organism-specific databases

HPAiHPA005561.

Interactioni

Protein-protein interaction databases

BioGridi109233. 1 interaction.
IntActiP43080. 1 interaction.
STRINGi9606.ENSP00000053469.

Structurei

3D structure databases

ProteinModelPortaliP43080.
SMRiP43080. Positions 5-185.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 4936EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini51 – 8636EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini87 – 12236EF-hand 3PROSITE-ProRule annotationAdd
BLAST
Domaini131 – 16636EF-hand 4PROSITE-ProRule annotationAdd
BLAST

Domaini

Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium levels are high. Binds Mg2+ when calcium levels are low.By similarity

Sequence similaritiesi

Contains 4 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiP43080.
KOiK08328.
PhylomeDBiP43080.
TreeFamiTF333971.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR033022. GUCA1A.
IPR028846. Recoverin.
[Graphical view]
PANTHERiPTHR23055. PTHR23055. 1 hit.
PTHR23055:SF13. PTHR23055:SF13. 1 hit.
PfamiPF00036. EF-hand_1. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43080-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGNVMEGKSV EELSSTECHQ WYKKFMTECP SGQLTLYEFR QFFGLKNLSP
60 70 80 90 100
SASQYVEQMF ETFDFNKDGY IDFMEYVAAL SLVLKGKVEQ KLRWYFKLYD
110 120 130 140 150
VDGNGCIDRD ELLTIIQAIR AINPCSDTTM TAEEFTDTVF SKIDVNGDGE
160 170 180 190 200
LSLEEFIEGV QKDQMLLDTL TRSLDLTRIV RRLQNGEQDE EGADEAAEAA

G
Length:201
Mass (Da):22,920
Last modified:January 23, 2007 - v3
Checksum:i063C6AD61BE44406
GO

Sequence cautioni

The sequence CAD92530 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti79 – 791A → G in AAA60541 (PubMed:7983048).Curated
Sequence conflicti79 – 791A → G in AAA60542 (PubMed:7983048).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti50 – 501P → L in COD3; some subjects may present a moderately severe cone-rod dystrophy; causes a decrease in the number of bound calcium ions from 3 to 2, without changing the activity profile. 2 Publications
Corresponds to variant rs104893968 [ dbSNP | Ensembl ].
VAR_010648
Natural varianti89 – 891E → K in COD3; exhibits an about 6-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060802
Natural varianti99 – 991Y → C in COD3; type 1A; alters calcium ion sensitivity, leading to the constitutive stimulating activity of GC1 at high calcium ion concentration, where normal GUCA1A inhibits it. 3 Publications
Corresponds to variant rs104893967 [ dbSNP | Ensembl ].
VAR_001372
Natural varianti100 – 1001D → E in COD3; exhibits an about 28-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060803
Natural varianti114 – 1141T → I in a patient with an atypical form of retinitis pigmentosa; unknown pathological significance. 1 Publication
Corresponds to variant rs771261841 [ dbSNP | Ensembl ].
VAR_060804
Natural varianti143 – 1431I → NT in COD3. 1 Publication
VAR_060805
Natural varianti151 – 1511L → F in COD3. 3 Publications
Corresponds to variant rs121434631 [ dbSNP | Ensembl ].
VAR_060806
Natural varianti155 – 1551E → G in COD3; constitutive activation of GC1. 1 Publication
VAR_012987
Natural varianti159 – 1591G → V in COD3; exhibits an about 18-fold shift of ionic calcium concentration at which the guanylate cyclase activity is halfmaximal. 1 Publication
VAR_060807

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36859 mRNA. Translation: AAA60541.1.
L36861 Genomic DNA. Translation: AAA60542.1.
AK125780 mRNA. Translation: BAG54246.1.
AL096814 Genomic DNA. Translation: CAB89167.1.
AL096814 Genomic DNA. Translation: CAD92530.1. Sequence problems.
CH471081 Genomic DNA. Translation: EAX04084.1.
BC031663 mRNA. Translation: AAH31663.1.
CCDSiCCDS4864.1.
PIRiC55331.
RefSeqiNP_000400.2. NM_000409.4.
NP_001305990.1. NM_001319061.1.
NP_001305991.1. NM_001319062.1.
XP_011512839.1. XM_011514537.2.
XP_011512841.1. XM_011514539.1.
UniGeneiHs.92858.

Genome annotation databases

EnsembliENST00000053469; ENSP00000053469; ENSG00000048545.
ENST00000372958; ENSP00000362049; ENSG00000048545.
ENST00000394237; ENSP00000377784; ENSG00000048545.
GeneIDi2978.
KEGGihsa:2978.
UCSCiuc003orx.4. human.

Cross-referencesi

Web resourcesi

Mutations of the GUCA1A gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36859 mRNA. Translation: AAA60541.1.
L36861 Genomic DNA. Translation: AAA60542.1.
AK125780 mRNA. Translation: BAG54246.1.
AL096814 Genomic DNA. Translation: CAB89167.1.
AL096814 Genomic DNA. Translation: CAD92530.1. Sequence problems.
CH471081 Genomic DNA. Translation: EAX04084.1.
BC031663 mRNA. Translation: AAH31663.1.
CCDSiCCDS4864.1.
PIRiC55331.
RefSeqiNP_000400.2. NM_000409.4.
NP_001305990.1. NM_001319061.1.
NP_001305991.1. NM_001319062.1.
XP_011512839.1. XM_011514537.2.
XP_011512841.1. XM_011514539.1.
UniGeneiHs.92858.

3D structure databases

ProteinModelPortaliP43080.
SMRiP43080. Positions 5-185.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109233. 1 interaction.
IntActiP43080. 1 interaction.
STRINGi9606.ENSP00000053469.

Polymorphism and mutation databases

BioMutaiGUCA1A.
DMDMi46577585.

Proteomic databases

PaxDbiP43080.
PeptideAtlasiP43080.
PRIDEiP43080.

Protocols and materials databases

DNASUi2978.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000053469; ENSP00000053469; ENSG00000048545.
ENST00000372958; ENSP00000362049; ENSG00000048545.
ENST00000394237; ENSP00000377784; ENSG00000048545.
GeneIDi2978.
KEGGihsa:2978.
UCSCiuc003orx.4. human.

Organism-specific databases

CTDi2978.
GeneCardsiGUCA1A.
HGNCiHGNC:4678. GUCA1A.
HPAiHPA005561.
MalaCardsiGUCA1A.
MIMi600364. gene.
602093. phenotype.
neXtProtiNX_P43080.
Orphaneti1872. Cone rod dystrophy.
1871. Progressive cone dystrophy.
PharmGKBiPA29062.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0044. Eukaryota.
COG5126. LUCA.
GeneTreeiENSGT00760000118820.
HOGENOMiHOG000233019.
HOVERGENiHBG108179.
InParanoidiP43080.
KOiK08328.
PhylomeDBiP43080.
TreeFamiTF333971.

Enzyme and pathway databases

ReactomeiR-HSA-2514859. Inactivation, recovery and regulation of the phototransduction cascade.

Miscellaneous databases

GeneWikiiGUCA1A.
GenomeRNAii2978.
PROiP43080.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000048545.
CleanExiHS_GUCA1A.
ExpressionAtlasiP43080. baseline and differential.
GenevisibleiP43080. HS.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR033022. GUCA1A.
IPR028846. Recoverin.
[Graphical view]
PANTHERiPTHR23055. PTHR23055. 1 hit.
PTHR23055:SF13. PTHR23055:SF13. 1 hit.
PfamiPF00036. EF-hand_1. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 3 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 3 hits.
PS50222. EF_HAND_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGUC1A_HUMAN
AccessioniPrimary (citable) accession number: P43080
Secondary accession number(s): B3KWT4, Q7Z6T1, Q9NU14
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.