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Protein

Guanylate cyclase soluble subunit alpha-3

Gene

GUCY1A3

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

Functioni

Catalytic activityi

GTP = 3',5'-cyclic GMP + diphosphate.3 Publications

Cofactori

Mg2+2 Publications, Mn2+2 PublicationsNote: Has also activity with Mn2+ (in vitro).2 Publications

Enzyme regulationi

Activated by nitric oxide in the presence of magnesium or manganese ions.1 Publication

GO - Molecular functioni

  • GTP binding Source: UniProtKB-KW
  • guanylate cyclase activity Source: UniProtKB
  • heme binding Source: InterPro
  • receptor activity Source: ProtInc

GO - Biological processi

  • blood circulation Source: ProtInc
  • cGMP biosynthetic process Source: UniProtKB
  • nitric oxide mediated signal transduction Source: ProtInc
  • positive regulation of cGMP biosynthetic process Source: Ensembl
  • regulation of blood pressure Source: Ensembl
  • relaxation of vascular smooth muscle Source: Ensembl
  • response to defense-related host nitric oxide production Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cGMP biosynthesis

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS09019-MONOMER.
BRENDAi4.6.1.2. 2681.
ReactomeiR-HSA-392154. Nitric oxide stimulates guanylate cyclase.
SIGNORiQ02108.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanylate cyclase soluble subunit alpha-3 (EC:4.6.1.23 Publications)
Short name:
GCS-alpha-3
Alternative name(s):
GCS-alpha-1
Soluble guanylate cyclase large subunit
Gene namesi
Name:GUCY1A3
Synonyms:GUC1A3, GUCSA3, GUCY1A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4685. GUCY1A3.

Subcellular locationi

GO - Cellular componenti

  • guanylate cyclase complex, soluble Source: UniProtKB
  • plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Moyamoya disease 6 with achalasia (MYMY6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Moyamoya disease, a progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults. MYMY6 is characterized by severe cerebral angiopathy and onset of severe achalasia in infancy or early childhood.
See also OMIM:615750

Organism-specific databases

DisGeNETi2982.
MalaCardsiGUCY1A3.
MIMi615750. phenotype.
OpenTargetsiENSG00000164116.
Orphaneti401945. Moyamoya disease with early-onset achalasia.
PharmGKBiPA29067.

Chemistry databases

ChEMBLiCHEMBL3137281.

Polymorphism and mutation databases

BioMutaiGUCY1A3.
DMDMi7404351.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000741101 – 690Guanylate cyclase soluble subunit alpha-3Add BLAST690

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei267PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02108.
PaxDbiQ02108.
PeptideAtlasiQ02108.
PRIDEiQ02108.

PTM databases

iPTMnetiQ02108.
PhosphoSitePlusiQ02108.

Expressioni

Tissue specificityi

Detected in brain cortex and lung (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000164116.
CleanExiHS_GUCY1A3.
ExpressionAtlasiQ02108. baseline and differential.
GenevisibleiQ02108. HS.

Organism-specific databases

HPAiCAB010887.
HPA056004.

Interactioni

Subunit structurei

The active enzyme is formed by a heterodimer of an alpha and a beta subunit. Heterodimer with GUCY1B3 (PubMed:9742212, PubMed:23505436, PubMed:24669844).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GUCY1B3Q021532EBI-3910037,EBI-6911707

Protein-protein interaction databases

BioGridi109237. 9 interactors.
IntActiQ02108. 3 interactors.
STRINGi9606.ENSP00000296518.

Structurei

Secondary structure

1690
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi472 – 487Combined sources16
Helixi490 – 496Combined sources7
Helixi499 – 519Combined sources21
Beta strandi523 – 525Combined sources3
Beta strandi533 – 540Combined sources8
Helixi545 – 560Combined sources16
Beta strandi568 – 570Combined sources3
Beta strandi573 – 587Combined sources15
Beta strandi589 – 591Combined sources3
Beta strandi593 – 598Combined sources6
Helixi599 – 609Combined sources11
Beta strandi616 – 618Combined sources3
Helixi620 – 626Combined sources7
Beta strandi632 – 636Combined sources5
Beta strandi655 – 660Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UVJX-ray2.08A/C468-690[»]
4NI2X-ray1.90A468-662[»]
ProteinModelPortaliQ02108.
SMRiQ02108.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini481 – 608Guanylate cyclasePROSITE-ProRule annotationAdd BLAST128

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
Contains 1 guanylate cyclase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4171. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000220903.
HOVERGENiHBG106603.
InParanoidiQ02108.
KOiK12318.
OMAiSEIPGIC.
OrthoDBiEOG091G04KV.
PhylomeDBiQ02108.
TreeFamiTF351403.

Family and domain databases

Gene3Di3.30.70.1230. 1 hit.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR011644. Heme_NO-bd.
IPR011645. HNOB_dom_associated.
IPR024096. NO_sig/Golgi_transp_ligand-bd.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF00211. Guanylate_cyc. 1 hit.
PF07700. HNOB. 1 hit.
PF07701. HNOBA. 1 hit.
[Graphical view]
SMARTiSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMiSSF111126. SSF111126. 1 hit.
SSF55073. SSF55073. 1 hit.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q02108-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MFCTKLKDLK ITGECPFSLL APGQVPNESS EEAAGSSESC KATVPICQDI
60 70 80 90 100
PEKNIQESLP QRKTSRSRVY LHTLAESICK LIFPEFERLN VALQRTLAKH
110 120 130 140 150
KIKESRKSLE REDFEKTIAE QAVAAGVPVE VIKESLGEEV FKICYEEDEN
160 170 180 190 200
ILGVVGGTLK DFLNSFSTLL KQSSHCQEAG KRGRLEDASI LCLDKEDDFL
210 220 230 240 250
HVYYFFPKRT TSLILPGIIK AAAHVLYETE VEVSLMPPCF HNDCSEFVNQ
260 270 280 290 300
PYLLYSVHMK STKPSLSPSK PQSSLVIPTS LFCKTFPFHF MFDKDMTILQ
310 320 330 340 350
FGNGIRRLMN RRDFQGKPNF EEYFEILTPK INQTFSGIMT MLNMQFVVRV
360 370 380 390 400
RRWDNSVKKS SRVMDLKGQM IYIVESSAIL FLGSPCVDRL EDFTGRGLYL
410 420 430 440 450
SDIPIHNALR DVVLIGEQAR AQDGLKKRLG KLKATLEQAH QALEEEKKKT
460 470 480 490 500
VDLLCSIFPC EVAQQLWQGQ VVQAKKFSNV TMLFSDIVGF TAICSQCSPL
510 520 530 540 550
QVITMLNALY TRFDQQCGEL DVYKVETIGD AYCVAGGLHK ESDTHAVQIA
560 570 580 590 600
LMALKMMELS DEVMSPHGEP IKMRIGLHSG SVFAGVVGVK MPRYCLFGNN
610 620 630 640 650
VTLANKFESC SVPRKINVSP TTYRLLKDCP GFVFTPRSRE ELPPNFPSEI
660 670 680 690
PGICHFLDAY QQGTNSKPCF QKKDVEDGNA NFLGKASGID
Length:690
Mass (Da):77,452
Last modified:May 30, 2000 - v2
Checksum:iDA1E14A5E11451CF
GO
Isoform 2 (identifier: Q02108-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     625-690: Missing.

Note: No experimental confirmation available.
Show »
Length:624
Mass (Da):70,184
Checksum:i73DD3A95B1CDC339
GO

Sequence cautioni

The sequence CAA47145 differs from that shown. Reason: Frameshift at positions 123, 127, 131, 162, 184, 529, 535, 678 and 680.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti44V → M in AAH28384 (PubMed:15489334).Curated1
Sequence conflicti124 – 127AAGV → QQS in CAA47145 (PubMed:1352257).Curated4
Sequence conflicti322Missing in CAA47145 (PubMed:1352257).Curated1
Sequence conflicti497C → R in AK309950 (PubMed:14702039).Curated1
Sequence conflicti554L → V in AAH28384 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04925725V → I.Corresponds to variant rs2170646dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045477625 – 690Missing in isoform 2. 1 PublicationAdd BLAST66

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66534 mRNA. Translation: CAA47145.1. Frameshift.
U58855 mRNA. Translation: AAB94794.1.
Y15723 mRNA. Translation: CAA75738.1.
AK309950 mRNA. No translation available.
AC104083 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04892.1.
CH471056 Genomic DNA. Translation: EAX04895.1.
CH471056 Genomic DNA. Translation: EAX04896.1.
CH471056 Genomic DNA. Translation: EAX04897.1.
BC028384 mRNA. Translation: AAH28384.1.
CCDSiCCDS34085.1. [Q02108-1]
CCDS54812.1. [Q02108-2]
PIRiS23098.
RefSeqiNP_000847.2. NM_000856.5. [Q02108-1]
NP_001124154.1. NM_001130682.2. [Q02108-1]
NP_001124155.1. NM_001130683.3. [Q02108-1]
NP_001124156.1. NM_001130684.2. [Q02108-1]
NP_001124159.1. NM_001130687.2. [Q02108-2]
NP_001243378.1. NM_001256449.1. [Q02108-1]
XP_005263012.1. XM_005262955.2. [Q02108-1]
XP_006714259.1. XM_006714196.2. [Q02108-1]
XP_006714260.1. XM_006714197.2. [Q02108-1]
UniGeneiHs.24258.
Hs.740815.

Genome annotation databases

EnsembliENST00000296518; ENSP00000296518; ENSG00000164116. [Q02108-1]
ENST00000455639; ENSP00000412201; ENSG00000164116. [Q02108-1]
ENST00000506455; ENSP00000424361; ENSG00000164116. [Q02108-1]
ENST00000511108; ENSP00000421493; ENSG00000164116. [Q02108-1]
ENST00000511507; ENSP00000426968; ENSG00000164116. [Q02108-2]
ENST00000513574; ENSP00000426040; ENSG00000164116. [Q02108-1]
GeneIDi2982.
KEGGihsa:2982.
UCSCiuc003iov.4. human. [Q02108-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66534 mRNA. Translation: CAA47145.1. Frameshift.
U58855 mRNA. Translation: AAB94794.1.
Y15723 mRNA. Translation: CAA75738.1.
AK309950 mRNA. No translation available.
AC104083 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04892.1.
CH471056 Genomic DNA. Translation: EAX04895.1.
CH471056 Genomic DNA. Translation: EAX04896.1.
CH471056 Genomic DNA. Translation: EAX04897.1.
BC028384 mRNA. Translation: AAH28384.1.
CCDSiCCDS34085.1. [Q02108-1]
CCDS54812.1. [Q02108-2]
PIRiS23098.
RefSeqiNP_000847.2. NM_000856.5. [Q02108-1]
NP_001124154.1. NM_001130682.2. [Q02108-1]
NP_001124155.1. NM_001130683.3. [Q02108-1]
NP_001124156.1. NM_001130684.2. [Q02108-1]
NP_001124159.1. NM_001130687.2. [Q02108-2]
NP_001243378.1. NM_001256449.1. [Q02108-1]
XP_005263012.1. XM_005262955.2. [Q02108-1]
XP_006714259.1. XM_006714196.2. [Q02108-1]
XP_006714260.1. XM_006714197.2. [Q02108-1]
UniGeneiHs.24258.
Hs.740815.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UVJX-ray2.08A/C468-690[»]
4NI2X-ray1.90A468-662[»]
ProteinModelPortaliQ02108.
SMRiQ02108.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109237. 9 interactors.
IntActiQ02108. 3 interactors.
STRINGi9606.ENSP00000296518.

Chemistry databases

ChEMBLiCHEMBL3137281.

PTM databases

iPTMnetiQ02108.
PhosphoSitePlusiQ02108.

Polymorphism and mutation databases

BioMutaiGUCY1A3.
DMDMi7404351.

Proteomic databases

MaxQBiQ02108.
PaxDbiQ02108.
PeptideAtlasiQ02108.
PRIDEiQ02108.

Protocols and materials databases

DNASUi2982.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296518; ENSP00000296518; ENSG00000164116. [Q02108-1]
ENST00000455639; ENSP00000412201; ENSG00000164116. [Q02108-1]
ENST00000506455; ENSP00000424361; ENSG00000164116. [Q02108-1]
ENST00000511108; ENSP00000421493; ENSG00000164116. [Q02108-1]
ENST00000511507; ENSP00000426968; ENSG00000164116. [Q02108-2]
ENST00000513574; ENSP00000426040; ENSG00000164116. [Q02108-1]
GeneIDi2982.
KEGGihsa:2982.
UCSCiuc003iov.4. human. [Q02108-1]

Organism-specific databases

CTDi2982.
DisGeNETi2982.
GeneCardsiGUCY1A3.
HGNCiHGNC:4685. GUCY1A3.
HPAiCAB010887.
HPA056004.
MalaCardsiGUCY1A3.
MIMi139396. gene.
615750. phenotype.
neXtProtiNX_Q02108.
OpenTargetsiENSG00000164116.
Orphaneti401945. Moyamoya disease with early-onset achalasia.
PharmGKBiPA29067.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4171. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000220903.
HOVERGENiHBG106603.
InParanoidiQ02108.
KOiK12318.
OMAiSEIPGIC.
OrthoDBiEOG091G04KV.
PhylomeDBiQ02108.
TreeFamiTF351403.

Enzyme and pathway databases

BioCyciZFISH:HS09019-MONOMER.
BRENDAi4.6.1.2. 2681.
ReactomeiR-HSA-392154. Nitric oxide stimulates guanylate cyclase.
SIGNORiQ02108.

Miscellaneous databases

ChiTaRSiGUCY1A3. human.
GeneWikiiGUCY1A3.
GenomeRNAii2982.
PROiQ02108.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164116.
CleanExiHS_GUCY1A3.
ExpressionAtlasiQ02108. baseline and differential.
GenevisibleiQ02108. HS.

Family and domain databases

Gene3Di3.30.70.1230. 1 hit.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR011644. Heme_NO-bd.
IPR011645. HNOB_dom_associated.
IPR024096. NO_sig/Golgi_transp_ligand-bd.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF00211. Guanylate_cyc. 1 hit.
PF07700. HNOB. 1 hit.
PF07701. HNOBA. 1 hit.
[Graphical view]
SMARTiSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMiSSF111126. SSF111126. 1 hit.
SSF55073. SSF55073. 1 hit.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGCYA3_HUMAN
AccessioniPrimary (citable) accession number: Q02108
Secondary accession number(s): D3DP19
, D6RDW3, O43843, Q8TAH3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: May 30, 2000
Last modified: November 30, 2016
This is version 159 of the entry and version 2 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

Miscellaneous

There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.