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Protein

Guanylate cyclase soluble subunit alpha-1

Gene

GUCY1A1

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

Functioni

Miscellaneous

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

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
  • signaling 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

Keywordsi

Molecular functionLyase
Biological processcGMP biosynthesis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

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-1Curated (EC:4.6.1.23 Publications)
Short name:
GCS-alpha-1
Alternative name(s):
Guanylate cyclase soluble subunit alpha-31 Publication
Short name:
GCS-alpha-3
Soluble guanylate cyclase large subunit
Gene namesi
Name:GUCY1A1Imported
Synonyms:GUC1A3, GUCSA3, GUCY1A3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164116.16
HGNCiHGNC:4685 GUCY1A1
MIMi139396 gene
neXtProtiNX_Q02108

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
MalaCardsiGUCY1A1
MIMi615750 phenotype
OpenTargetsiENSG00000164116
Orphaneti401945 Moyamoya disease with early-onset achalasia
PharmGKBiPA29067

Chemistry databases

ChEMBLiCHEMBL3137281
GuidetoPHARMACOLOGYi1288

Polymorphism and mutation databases

BioMutaiGUCY1A3
DMDMi7404351

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000741101 – 690Guanylate cyclase soluble subunit alpha-1Add 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 GUCY1B1 (PubMed:9742212, PubMed:23505436, PubMed:24669844).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GUCY1B1Q021532EBI-3910037,EBI-6911707

Protein-protein interaction databases

BioGridi109237, 9 interactors
CORUMiQ02108
IntActiQ02108, 3 interactors
STRINGi9606.ENSP00000296518

Chemistry databases

BindingDBiQ02108

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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.70.1230, 1 hit
3.90.1520.10, 1 hit
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR038158 H-NOX_domain_sf
IPR011644 Heme_NO-bd
IPR011645 HNOB_dom_associated
IPR024096 NO_sig/Golgi_transp_ligand-bd
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF00211 Guanylate_cyc, 1 hit
PF07700 HNOB, 1 hit
PF07701 HNOBA, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 1 hit
SUPFAMiSSF111126 SSF111126, 1 hit
SSF55073 SSF55073, 1 hit
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 1 hit

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 dbSNP:rs2170646Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiGCYA1_HUMAN
AccessioniPrimary (citable) accession number: Q02108
Secondary accession number(s): D3DP19
, D6RDW3, O43843, Q8TAH3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: May 30, 2000
Last modified: May 23, 2018
This is version 169 of the entry and version 2 of the sequence. See 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

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

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