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GUCY1A1 guanylate cyclase 1 soluble subunit alpha 1 [ Homo sapiens (human) ]

Gene ID: 2982, updated on 20-Dec-2019

Summary

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Official Symbol
GUCY1A1provided by HGNC
Official Full Name
guanylate cyclase 1 soluble subunit alpha 1provided by HGNC
Primary source
HGNC:HGNC:4685
See related
Ensembl:ENSG00000164116 MIM:139396
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
GUCA3; MYMY6; GC-SA3; GUC1A3; GUCSA3; GUCY1A3
Summary
Soluble guanylate cyclases are heterodimeric proteins that catalyze the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. The protein encoded by this gene is an alpha subunit of this complex and it interacts with a beta subunit to form the guanylate cyclase enzyme, which is activated by nitric oxide. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Expression
Ubiquitous expression in prostate (RPKM 11.3), heart (RPKM 8.5) and 24 other tissues See more
Orthologs
mouse all

Genomic context

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See GUCY1A1 in Genome Data Viewer
Location:
4q32.1
Exon count:
13
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (155666710..155737059)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (156587862..156658214)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377505 Neighboring gene uncharacterized LOC105377504 Neighboring gene uncharacterized LOC107984032 Neighboring gene uncharacterized LOC105377506 Neighboring gene guanylate cyclase 1 soluble subunit beta 1 Neighboring gene uncharacterized LOC105377507 Neighboring gene acid sensing ion channel subunit family member 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells. Zhou J, et al. PLoS One, 2017. PMID 28859127, Free PMC Article
  2. Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus. Kessler T, et al. Circulation, 2017 Aug 1. PMID 28487391, Free PMC Article
  3. Stimulators of the soluble guanylyl cyclase: promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants. Wobst J, et al. Basic Res Cardiol, 2016 Jul. PMID 27342234
  4. Disrupted nitric oxide signaling due to GUCY1A3 mutations increases risk for moyamoya disease, achalasia and hypertension. Wallace S, et al. Clin Genet, 2016 Oct. PMID 26777256, Free PMC Article
  5. α1-A680T variant in GUCY1A3 as a candidate conferring protection from pulmonary hypertension among Kyrgyz highlanders. Wilkins MR, et al. Circ Cardiovasc Genet, 2014 Dec. PMID 25373139

See all (44) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genetic predisposition to enhanced nitric oxide signaling was associated with reduced blood pressure, improved renal and pulmonary function, and significantly reduced risks of coronary heart disease in people with rs7692387 GUCY1A3 variant.
    Title: Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.
  2. data have provided some evidence for an alteration in the expression of alpha1 and beta1 oluble guanylyl cyclase alternative splicing forms which may contribute to the loss of sGC functions in breast cancer
    Title: Differential expression of alternative transcripts of soluble guanylyl cyclase, GYCY1a3 and GUCY1b3 genes, in the malignant and benign breast tumors.
  3. GCAP1 and GCAP2 bound to different regions on the target guanylate cyclase type 1 with submicromolar affinity (apparent KD-values of 663 +/- 121 nM and 231 +/- 63 nM for Ca(2+)-free GCAP1 and GCAP2, respectively).
    Title: Label-free quantification of calcium-sensor targeting to photoreceptor guanylate cyclase and rhodopsin kinase by backscattering interferometry.
  4. Human Red Blood Cells carry catalytically active alpha1beta1-soluble guanylate cyclase (isoform 1). Red cell soluble guanylate cyclase activity is fully preserved in patients with stable coronary artery disease.
    Title: Identification of a soluble guanylate cyclase in RBCs: preserved activity in patients with coronary artery disease.
  5. Peptide B-8R killed both androgen-dependent and androgen-independent prostate cancer cells that expressed sGCalpha1, but not cells that do not express this gene. Peptide B-8R induced apoptosis of prostate cancer cells.
    Title: Peptide B targets soluble guanylyl cyclase α1 and kills prostate cancer cells.
  6. In conclusion, rare coding variants in GUCY1A3 lead to reduced cGMP formation which can be rescued by a soluble guanylyl cyclase stimulator in vitro
    Title: Stimulators of the soluble guanylyl cyclase: promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants.
  7. Rs7692387 is located in an intronic site that modulates GUCY1A3 promoter activity. The transcription factor ZEB1 binds preferentially to the nonrisk allele, leading to an increase in GUCY1A3 expression, higher sGC levels, and higher sGC activity after stimulation.
    Title: Functional Characterization of the <i>GUCY1A3</i> Coronary Artery Disease Risk Locus.
  8. Mutations in the GUCY1A3 gene are associated with moyamoya disease, achalasia, and hypertension.
    Title: Disrupted nitric oxide signaling due to GUCY1A3 mutations increases risk for moyamoya disease, achalasia and hypertension.
  9. Expression of the alpha1-A680T sGC variant in reporter cells resulted in higher cyclic guanosine monophosphate production compared with the wild-type enzyme and the purified alpha1-A680T sGC exhibited enhanced sensitivity to nitric oxide in vitro.
    Title: α1-A680T variant in GUCY1A3 as a candidate conferring protection from pulmonary hypertension among Kyrgyz highlanders.
  10. Dynamic interplay between hsp90, apo-sGC-beta1, and sGC-alpha1 in response to NO is unprecedented and represent new steps by which cells can modulate the heme content and activity of sGC for signaling cascades.
    Title: Nitric oxide and heat shock protein 90 activate soluble guanylate cyclase by driving rapid change in its subunit interactions and heme content.
Submit: New GeneRIF Correction See all GeneRIFs (21)

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

Associated conditions

Description Tests
Moyamoya disease 6 with achalasia
MedGen: C3810403 OMIM: 615750 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
NHGRI GWA Catalog
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
NHGRI GWA Catalog
Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension.
NHGRI GWA Catalog
Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease.
NHGRI GWA Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat potentiates NMDA-evoked (Ca2+)I responses involve LRP and a Src family kinase via the NOS/sGC/PKG pathway PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
GTP binding IEA
Inferred from Electronic Annotation
more info
  
guanylate cyclase activity IDA
Inferred from Direct Assay
more info
 PubMed 
heme binding IEA
Inferred from Electronic Annotation
more info
  
protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
signaling receptor activity TAS
Traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
blood circulation TAS
Traceable Author Statement
more info
 PubMed 
cGMP biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
nitric oxide mediated signal transduction TAS
Traceable Author Statement
more info
 PubMed 
positive regulation of nitric oxide mediated signal transduction IEA
Inferred from Electronic Annotation
more info
  
regulation of blood pressure IEA
Inferred from Electronic Annotation
more info
  
relaxation of vascular smooth muscle IEA
Inferred from Electronic Annotation
more info
  
response to defense-related host nitric oxide production IEA
Inferred from Electronic Annotation
more info
  
retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
GABA-ergic synapse IEA
Inferred from Electronic Annotation
more info
  
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
guanylate cyclase complex, soluble IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
guanylate cyclase soluble subunit alpha-1
Names
GC-S-alpha-1
GCS-alpha-3
guanylate cyclase 1, soluble, alpha 3
soluble guanylate cyclase large subunit
NP_000847.2
NP_001124154.1
NP_001124155.1
NP_001124156.1
NP_001124157.1
NP_001124159.1
NP_001243378.1
XP_005263012.1
XP_005263013.1
XP_005263014.1
XP_006714259.1
XP_006714260.1
XP_011530202.1

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

  1. NG_034128.1 RefSeqGene

    Range
    5139..75350
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000856.6 → NP_000847.2  guanylate cyclase soluble subunit alpha-1 isoform A

    See identical proteins and their annotated locations for NP_000847.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (A). Variants 1, 2, 3, 4, and 8 all encode the same isoform (A).
    Source sequence(s)
    AC104083, CD671731, Y15723
    Consensus CDS
    CCDS34085.1
    UniProtKB/Swiss-Prot
    Q02108
    Related
    ENSP00000421493.1, ENST00000511108.5
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  2. NM_001130682.3 → NP_001124154.1  guanylate cyclase soluble subunit alpha-1 isoform A

    See identical proteins and their annotated locations for NP_001124154.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1, and encodes isoform A. Variants 1, 2, 3, 4, and 8 all encode the same isoform (A).
    Source sequence(s)
    AC104083, CD671731, DA793192, Y15723
    Consensus CDS
    CCDS34085.1
    UniProtKB/Swiss-Prot
    Q02108
    Related
    ENSP00000424361.1, ENST00000506455.5
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  3. NM_001130683.4 → NP_001124155.1  guanylate cyclase soluble subunit alpha-1 isoform A

    See identical proteins and their annotated locations for NP_001124155.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1, and encodes isoform A. Variants 1, 2, 3, 4, and 8 all encode the same isoform (A).
    Source sequence(s)
    AC104083, AK226125, BX649180, CD671731, DA518091
    Consensus CDS
    CCDS34085.1
    UniProtKB/Swiss-Prot
    Q02108
    Related
    ENSP00000296518.7, ENST00000296518.11
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  4. NM_001130684.3 → NP_001124156.1  guanylate cyclase soluble subunit alpha-1 isoform A

    See identical proteins and their annotated locations for NP_001124156.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1, and encodes isoform A. Variants 1, 2, 3, 4, and 8 all encode the same isoform (A).
    Source sequence(s)
    AC104083, CD671731, Y15723
    Consensus CDS
    CCDS34085.1
    UniProtKB/Swiss-Prot
    Q02108
    Related
    ENSP00000426040.1, ENST00000513574.1
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  5. NM_001130685.3 → NP_001124157.1  guanylate cyclase soluble subunit alpha-1 isoform B

    See identical proteins and their annotated locations for NP_001124157.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (B) is shorter at the N-terminus compared to isoform A.
    Source sequence(s)
    AC104083, AK226125, CD671731, DA518091
    Related
    ENSP00000377418.3, ENST00000393832.7
    Conserved Domains (4) summary
    smart00044
    Location:210 → 399
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:237 → 408
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07701
    Location:42 → 231
    HNOBA; Heme NO binding associated
    cl01153
    Location:395 → 441
    NapB; Nitrate reductase cytochrome c-type subunit (NapB)

  6. NM_001130687.2 → NP_001124159.1  guanylate cyclase soluble subunit alpha-1 isoform D

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) differs in the 3' UTR and coding sequence compared to variant 1. The resulting isoform (D) is shorter at the C-terminus compared to isoform A.
    Source sequence(s)
    AC104083, AK309950, DA793192
    Consensus CDS
    CCDS54812.1
    UniProtKB/Swiss-Prot
    Q02108
    Related
    ENSP00000426968.1, ENST00000511507.5
    Conserved Domains (4) summary
    smart00044
    Location:445 → 624
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:472 → 624
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  7. NM_001256449.2 → NP_001243378.1  guanylate cyclase soluble subunit alpha-1 isoform A

    See identical proteins and their annotated locations for NP_001243378.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) differs in the 5' UTR, compared to variant 1, and encodes isoform A. Variants 1, 2, 3, 4, and 8 all encode the same isoform (A).
    Source sequence(s)
    AC104083, AK096588, CD671731, Y15723
    Consensus CDS
    CCDS34085.1
    UniProtKB/Swiss-Prot
    Q02108
    UniProtKB/TrEMBL
    B3KU69
    Related
    ENSP00000412201.2, ENST00000455639.6
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    Range
    155666710..155737059
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006714196.2 → XP_006714259.1  guanylate cyclase soluble subunit alpha-1 isoform X1

    See identical proteins and their annotated locations for XP_006714259.1

    UniProtKB/Swiss-Prot
    Q02108
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  2. XM_005262957.3 → XP_005263014.1  guanylate cyclase soluble subunit alpha-1 isoform X2

    See identical proteins and their annotated locations for XP_005263014.1

    Conserved Domains (4) summary
    smart00044
    Location:210 → 399
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:237 → 408
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07701
    Location:42 → 231
    HNOBA; Heme NO binding associated
    cl01153
    Location:395 → 441
    NapB; Nitrate reductase cytochrome c-type subunit (NapB)

  3. XM_005262956.3 → XP_005263013.1  guanylate cyclase soluble subunit alpha-1 isoform X2

    See identical proteins and their annotated locations for XP_005263013.1

    Conserved Domains (4) summary
    smart00044
    Location:210 → 399
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:237 → 408
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07701
    Location:42 → 231
    HNOBA; Heme NO binding associated
    cl01153
    Location:395 → 441
    NapB; Nitrate reductase cytochrome c-type subunit (NapB)

  4. XM_005262955.3 → XP_005263012.1  guanylate cyclase soluble subunit alpha-1 isoform X1

    See identical proteins and their annotated locations for XP_005263012.1

    UniProtKB/Swiss-Prot
    Q02108
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

  5. XM_011531900.2 → XP_011530202.1  guanylate cyclase soluble subunit alpha-1 isoform X2

    See identical proteins and their annotated locations for XP_011530202.1

    Conserved Domains (4) summary
    smart00044
    Location:210 → 399
    CYCc; Adenylyl- / guanylyl cyclase, catalytic domain
    pfam00211
    Location:237 → 408
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07701
    Location:42 → 231
    HNOBA; Heme NO binding associated
    cl01153
    Location:395 → 441
    NapB; Nitrate reductase cytochrome c-type subunit (NapB)

  6. XM_006714197.2 → XP_006714260.1  guanylate cyclase soluble subunit alpha-1 isoform X1

    See identical proteins and their annotated locations for XP_006714260.1

    UniProtKB/Swiss-Prot
    Q02108
    Conserved Domains (3) summary
    pfam00211
    Location:472 → 643
    Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain
    pfam07700
    Location:126 → 235
    HNOB; Haem-NO-binding
    pfam07701
    Location:277 → 466
    HNOBA; Heme NO binding associated

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001130686.1: Suppressed sequence

    Description
    NM_001130686.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q02108.2 GenPept UniProtKB/Swiss-Prot:Q02108

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