GUCY1A2 (guanylate cyclase 1 soluble subunit alpha 2)

Gene

• Entrez ID: 2977
• Gene name: Guanylate cyclase 1 soluble subunit alpha 2
• Gene symbol: GUCY1A2
• Synonyms (NCBI Gene): GC-SA2, GUC1A2
• Chromosome: 11
• Chromosome location: 11q22.3
• 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 guanylat

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017344	hsa-miR-335-5p	Microarray	18185580
MIRT497100	hsa-miR-330-3p	PAR-CLIP	22291592
MIRT497099	hsa-miR-3614-5p	PAR-CLIP	22291592
MIRT497098	hsa-miR-6500-3p	PAR-CLIP	22291592
MIRT497097	hsa-miR-1288-5p	PAR-CLIP	22291592
MIRT497096	hsa-miR-145-3p	PAR-CLIP	22291592
MIRT486338	hsa-miR-6512-5p	PAR-CLIP	23592263
MIRT486339	hsa-miR-625-3p	PAR-CLIP	23592263
MIRT486337	hsa-miR-7705	PAR-CLIP	23592263
MIRT486336	hsa-miR-3917	PAR-CLIP	23592263
MIRT486335	hsa-miR-3619-3p	PAR-CLIP	23592263
MIRT497100	hsa-miR-330-3p	PAR-CLIP	22291592
MIRT497099	hsa-miR-3614-5p	PAR-CLIP	22291592
MIRT497098	hsa-miR-6500-3p	PAR-CLIP	22291592
MIRT497097	hsa-miR-1288-5p	PAR-CLIP	22291592
MIRT497096	hsa-miR-145-3p	PAR-CLIP	22291592
MIRT486338	hsa-miR-6512-5p	PAR-CLIP	23592263
MIRT486339	hsa-miR-625-3p	PAR-CLIP	23592263
MIRT486337	hsa-miR-7705	PAR-CLIP	23592263
MIRT486336	hsa-miR-3917	PAR-CLIP	23592263
MIRT486335	hsa-miR-3619-3p	PAR-CLIP	23592263
MIRT1038408	hsa-miR-3065-5p	CLIP-seq
MIRT1038409	hsa-miR-3908	CLIP-seq
MIRT1038410	hsa-miR-4311	CLIP-seq
MIRT1038411	hsa-miR-513c	CLIP-seq
MIRT1038412	hsa-miR-514b-5p	CLIP-seq
MIRT1038409	hsa-miR-3908	CLIP-seq
MIRT2450893	hsa-miR-2054	CLIP-seq
MIRT2450893	hsa-miR-2054	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004383	Function	Guanylate cyclase activity	IBA
GO:0004383	Function	Guanylate cyclase activity	IEA
GO:0004383	Function	Guanylate cyclase activity	TAS	1683630
GO:0005515	Function	Protein binding	IPI	24550280, 30126976, 32296183
GO:0005525	Function	GTP binding	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006182	Process	CGMP biosynthetic process	IEA
GO:0007165	Process	Signal transduction	TAS	1683630
GO:0007263	Process	Nitric oxide mediated signal transduction	IEA
GO:0008074	Component	Guanylate cyclase complex, soluble	IBA
GO:0009190	Process	Cyclic nucleotide biosynthetic process	IEA
GO:0010750	Process	Positive regulation of nitric oxide mediated signal transduction	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016849	Function	Phosphorus-oxygen lyase activity	IEA
GO:0019934	Process	CGMP-mediated signaling	IBA
GO:0020037	Function	Heme binding	IEA
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0070482	Process	Response to oxygen levels	IBA

Other IDs

• MIM: 601244
• HGNC: 4684
• e!Ensembl: ENSG00000152402

Protein

• UniProt ID: P33402
• Protein name: Guanylate cyclase soluble subunit alpha-2 (GCS-alpha-2) (EC 4.6.1.2)
• Protein function: Has guanylyl cyclase on binding to the beta-1 subunit.; Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07700	HNOB	105 → 270	Haem-NO-binding	Domain
  PF07701	HNOBA	316 → 506	Heme NO binding associated	Domain
  PF00211	Guanylate_cyc	512 → 699	Adenylate and Guanylate cyclase catalytic domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Isoform 1 is expressed in fetal brain, liver, colon, endothelium and testis. Isoform 2 is expressed only in liver, colon and endothelium.
• Sequence:

  MSRRKISSESFSSLGSDYLETSPEEEGECPLSRLCWNGSRSPPGPLEPSPAAAAAAAAPA
  PTPAASAAAAAATAGARRVQRRRRVNLDSLGESISRLTAPSPQTIQQTLKRTLQYYEHQV
  IGYRDAEKNFHNISNRCSYADHSNKEEIEDVSGILQCTANILGLKFEEIQKRFGEEFFNI
  CFHENERVLRAVGGTLQDFFNGFDALLEHIRTSFGKQATLESPSFLCKELPEGTLMLHYF
  HPHHIVGFAMLGMIKAAGKKIYRLDVEVEQVANEKLCSDVSNPGNCSCLTFLIKECENTN
  IMKNLPQGTSQVPADLRISINTFCRAFPFHLMFDPSMSVLQLGEGLRKQLRCDTHKVLKF
  EDCFEIVSPKVNATFERVLLRLSTPFVIRTKPEASGSENKDKVMEVKGQMIHVPESNSIL
  FLGSPCVDKLDELMGRGLHLSDIPIHDATRDVILVGEQAKAQDGLKKRMDKLKATLERTH
  QALEEEKKKTVDLLYSIFPGDVAQQLWQGQQVQARKFDDVTMLFSDIVGFTAICAQCTPM
  QVISMLNELYTRFDHQCGFLDIYKVETIGDAYCVAAGLHRKSLCHAKPIALMALKMMELS
  EEVLTPDGRPIQMRIGIHSGSVLAGVVGVRMPRYCLFGNNVTLASKFESGSHPRRINVSP
  TTYQLLKREESFTFIPRSREELPDNFPKEIPGICYFLEVRTGPKPPKPSLSSSRIKKVSY
  NIGTMFLRETSL

• Sequence length: 732

Pathways

KEGG:

Purine metabolism
Metabolic pathways
cGMP-PKG signaling pathway
Vascular smooth muscle contraction
Gap junction
Platelet activation
Circadian entrainment
Long-term depression
Oxytocin signaling pathway
Renin secretion
Salivary secretion

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANXIETY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CENTRAL NERVOUS SYSTEM INFECTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIAL NEOPLASM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GESTATIONAL DIABETES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	28767591	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	GWASDB_DG	22843504		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	CTD_human_DG	18507500		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	CTD_human_DG	18507500, 21278247		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal Neoplasms	CTD_human_DG	18507500, 21278247		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of breast	Breast Cancer	CTD_human_DG	18507500		★☆☆☆☆ Found in Text Mining only
Mammary Carcinoma, Human	Marfan Syndrome	CTD_human_DG	18507500		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	CTD_human_DG	18507500		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms, Human	Mammary Neoplasms	CTD_human_DG	18507500		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	35036435	Associate	★☆☆☆☆ Found in Text Mining only