Gene Symbol: GUCY1A1
Description: guanylate cyclase 1 soluble subunit alpha 1
Alias: GC-SA3, GUC1A3, GUCA3, GUCSA3, GUCY1A3, MYMY6, guanylate cyclase soluble subunit alpha-1, GC-S-alpha-1, GCS-alpha-3, guanylate cyclase 1, soluble, alpha 3, soluble guanylate cyclase large subunit
Species: human
Products:     GUCY1A1

Top Publications

  1. Cai C, Hsieh C, Gao S, Kannan A, Bhansali M, Govardhan K, et al. Soluble guanylyl cyclase ?1 and p53 cytoplasmic sequestration and down-regulation in prostate cancer. Mol Endocrinol. 2012;26:292-307 pubmed publisher
  2. Saino M, Maruyama T, Sekiya T, Kayama T, Murakami Y. Inhibition of angiogenesis in human glioma cell lines by antisense RNA from the soluble guanylate cyclase genes, GUCY1A3 and GUCY1B3. Oncol Rep. 2004;12:47-52 pubmed
    ..U-87MG, overproduced cyclic GMP (cGMP) and showed increased expression of both or either subunits of soluble GC1, GUCY1A3 and GUCY1B3...
  3. Mohammadoo Khorasani M, Karami Tehrani F, Parizadeh S, Atri M. Differential expression of alternative transcripts of soluble guanylyl cyclase, GYCY1a3 and GUCY1b3 genes, in the malignant and benign breast tumors. Nitric Oxide. 2019;83:65-71 pubmed publisher
    ..Each subunit is encoded by a separate gene, GUCY1a3 and GUCY1b3, correspondingly...
  4. Sheen J, Yu H, Tiao M, Chen C, Huang L, Chang H, et al. Prenatal dexamethasone-induced programmed hypertension and renal programming. Life Sci. 2015;132:41-8 pubmed publisher
    ..Among these genes, Npr3, Ptgs2, Agt, Edn3, Ephx2, Agtr1b, and Gucy1a3 are associated with endothelium-derived hyperpolarizing and contractile factors (EDHF and EDCF)...
  5. Midttun H, Ramsay A, Mueller Harvey I, Williams A. Cocoa procyanidins modulate transcriptional pathways linked to inflammation and metabolism in human dendritic cells. Food Funct. 2018;9:2883-2890 pubmed publisher
    ..of genes encoding cytokines and chemokines such as CXCL1, but also genes involved in the cGMP pathway such as GUCY1A3 (encoding guanylate cyclase soluble subunit alpha-3)...
  6. De Pauw A, Massion P, Sekkali B, André E, Dubroca C, Kmecova J, et al. Paracrine nitric oxide induces expression of cardiac sarcomeric proteins in adult progenitor cells through soluble guanylyl cyclase/cyclic-guanosine monophosphate and Wnt/?-catenin inhibition. Cardiovasc Res. 2016;112:478-90 pubmed publisher
    ..The optimal time window for NO efficacy coincided with up-regulation of CPC expression of Gucy1a3 (coding the alpha1 subunit of guanylyl cyclase)...
  7. Baburski A, Sokanovic S, Andric S, Kostic T. Aging has the opposite effect on cAMP and cGMP circadian variations in rat Leydig cells. J Comp Physiol B. 2017;187:613-623 pubmed publisher
    ..Aging stimulates expression of genes responsible for cGMP production (Nos2, Gucy1a3 and Gucy1b3/GUCYB3) and degradation (Pde5a, Pde6a and Pde6h) but the overall net effect is elevation of cGMP ..
  8. Hartmann K, Seweryn M, Handelman S, Rempała G, Sadee W. Non-linear interactions between candidate genes of myocardial infarction revealed in mRNA expression profiles. BMC Genomics. 2016;17:738 pubmed publisher
    ..Two pairs replicate between CATHGEN and FHS (CNNM2|GUCY1A3 and CNNM2|ZEB2)...
  9. Segura Puimedon M, Mergia E, Al Hasani J, Aherrahrou R, Stoelting S, Kremer F, et al. Proatherosclerotic Effect of the ?1-Subunit of Soluble Guanylyl Cyclase by Promoting Smooth Muscle Phenotypic Switching. Am J Pathol. 2016;186:2220-2231 pubmed publisher
    ..b>GUCY1A3, encoding the ?1 subunit, was identified as a risk gene for coronary artery disease and myocardial infarction, ..

More Information


  1. Wobst J, Schunkert H, Kessler T. Genetic alterations in the NO-cGMP pathway and cardiovascular risk. Nitric Oxide. 2018;76:105-112 pubmed publisher
    ..The GUCY1A3 gene encoding the α1 subunit of the soluble guanylyl cyclase (sGC) resides at one of these loci and ..
  2. Rippe C, Zhu B, Krawczyk K, Bavel E, Albinsson S, Sjölund J, et al. Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway. Sci Rep. 2017;7:1334 pubmed publisher
    ..resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC)...
  3. Guo Y, Nie H, Sun L, Zhang G, Deng K, Fan Y, et al. Effects of diet and arginine treatment during the luteal phase on ovarian NO/PGC-1α signaling in ewes. Theriogenology. 2017;96:76-84 pubmed publisher
    ..05). GUCY1A3 mRNA levels were significantly increased in RG and AG as compared to those in CG ewes (P < 0...
  4. Sharin V, Mujoo K, Kots A, Martin E, Murad F, Sharina I. Nitric oxide receptor soluble guanylyl cyclase undergoes splicing regulation in differentiating human embryonic cells. Stem Cells Dev. 2011;20:1287-93 pubmed publisher
    ..Together, our data suggest that alternative splicing of sGC subunits is associated with differentiation of hES cells. ..
  5. Ghosh A, Stasch J, Papapetropoulos A, Stuehr D. Nitric oxide and heat shock protein 90 activate soluble guanylate cyclase by driving rapid change in its subunit interactions and heme content. J Biol Chem. 2014;289:15259-71 pubmed publisher
    ..Such dynamic interplay between hsp90, apo-sGC-?1, and sGC-?1 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. ..
  6. Herve D, Philippi A, Belbouab R, Zerah M, Chabrier S, Collardeau Frachon S, et al. Loss of ?1?1 soluble guanylate cyclase, the major nitric oxide receptor, leads to moyamoya and achalasia. Am J Hum Genet. 2014;94:385-94 pubmed publisher
    ..This syndrome is associated in all three families with homozygous mutations in GUCY1A3, which encodes the ?1 subunit of soluble guanylate cyclase (sGC), the major receptor for nitric oxide (NO)...
  7. Giuili G, Roechel N, Scholl U, Mattei M, Guellaen G. Colocalization of the genes coding for the alpha 3 and beta 3 subunits of soluble guanylyl cyclase to human chromosome 4 at q31.3-q33. Hum Genet. 1993;91:257-60 pubmed
    ..3-4q33 region, with the maximal signal in the 4q32 band. The colocalization of both genes in 4q32 represents an interesting feature for the coordinated regulation of expression of both GC-S subunits. ..
  8. Kessler T, Wobst J, Wolf B, Eckhold J, Vilne B, Hollstein R, et al. Functional Characterization of the GUCY1A3 Coronary Artery Disease Risk Locus. Circulation. 2017;136:476-489 pubmed publisher
    ..1 has been genome-wide significantly associated with coronary artery disease risk. The locus encompasses GUCY1A3, which encodes the ?1 subunit of the soluble guanylyl cyclase (sGC), a key enzyme in the nitric ..
  9. Wobst J, von Ameln S, Wolf B, Wierer M, Dang T, Sager H, et al. Stimulators of the soluble guanylyl cyclase: promising functional insights from rare coding atherosclerosis-related GUCY1A3 variants. Basic Res Cardiol. 2016;111:51 pubmed publisher
    ..Genetic alterations of the GUCY1A3 gene, which encodes the α1 subunit of the sGC, are associated with coronary artery disease...
  10. Wilkins M, Aldashev A, Wharton J, Rhodes C, Vandrovcova J, Kasperaviciute D, et al. α1-A680T variant in GUCY1A3 as a candidate conferring protection from pulmonary hypertension among Kyrgyz highlanders. Circ Cardiovasc Genet. 2014;7:920-9 pubmed publisher
    ..A novel missense mutation in GUCY1A3 in 3 subjects with a normal mean pulmonary artery pressure encodes an α1-A680T soluble guanylate cyclase (sGC) ..
  11. Allerston C, von Delft F, Gileadi O. Crystal structures of the catalytic domain of human soluble guanylate cyclase. PLoS ONE. 2013;8:e57644 pubmed publisher
    ..This indicates the possibility of developing a new class of small-molecule modulators of guanylate cyclase activity targeting the catalytic domain. ..
  12. Zhou Y, Zheng J, Gu X, Li W, Saunders G. A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements?. Gene. 2000;245:319-28 pubmed
  13. Yoo B, Lamarre I, Martin J, Negrerie M. Quaternary structure controls ligand dynamics in soluble guanylate cyclase. J Biol Chem. 2012;287:6851-9 pubmed publisher
    ..These strains are likely involved in the transmission of the energy and relaxation toward the activated state after Fe(2+)-His bond breaking. This also reveals the heme domain plasticity modulated by the associated domains and subunit. ..
  14. Meurer S, Pioch S, Wagner K, Muller Esterl W, Gross S. AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase. J Biol Chem. 2004;279:49346-54 pubmed
    ..Our findings may hint to a potential role of AGAP1 in integrating signals from Arf, NO/cGMP, and tyrosine kinase signaling pathways. ..
  15. Ahrens I, Habersberger J, Baumlin N, Qian H, Smith B, Stasch J, et al. Measuring oxidative burden and predicting pharmacological response in coronary artery disease patients with a novel direct activator of haem-free/oxidised sGC. Atherosclerosis. 2011;218:431-4 pubmed publisher
    ..039, respectively) between CAD and non-CAD patients. We describe platelet-based assays that allow the determination of patients' oxidative status and thus allow the prediction of pharmacological response to direct sGC activators. ..
  16. Zhong F, Pan J, Liu X, Wang H, Ying T, Su J, et al. A novel insight into the heme and NO/CO binding mechanism of the alpha subunit of human soluble guanylate cyclase. J Biol Inorg Chem. 2011;16:1227-39 pubmed publisher
    ..These results are beneficial for understanding the overall structure of the heme binding site of the human sGC and the NO/CO signaling mechanism. ..
  17. Giuili G, Scholl U, Bulle F, Guellaen G. Molecular cloning of the cDNAs coding for the two subunits of soluble guanylyl cyclase from human brain. FEBS Lett. 1992;304:83-8 pubmed
    ..Malekewitz, J., Böhme, E., and Schultz, G. (1991) FEBS Lett. 292, 217-222) revealed only 34% homology. This result demonstrates the existence of a novel large subunit isoform for soluble guanylyl cyclase in human tissues. ..
  18. Papapetropoulos A, Cziraki A, Rubin J, Stone C, Catravas J. cGMP accumulation and gene expression of soluble guanylate cyclase in human vascular tissue. J Cell Physiol. 1996;167:213-21 pubmed
    ..We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (alpha 3) and a small (beta 3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation. ..
  19. Zabel U, Weeger M, La M, Schmidt H. Human soluble guanylate cyclase: functional expression and revised isoenzyme family. Biochem J. 1998;335 ( Pt 1):51-7 pubmed
    ..Having access to the human key enzyme of NO signalling will now permit the study of novel sGC-modulating compounds with therapeutic potential. ..
  20. Zhou J, Gao S, Hsieh C, Malla M, Shemshedini L. Peptide B targets soluble guanylyl cyclase ?1 and kills prostate cancer cells. PLoS ONE. 2017;12:e0184088 pubmed publisher
    ..Thus, future work will be directed at defining the mechanism of cytotoxic action of Peptide B-8R against prostate cancer cells. ..
  21. Behrends S, Vehse K, Scholz H, Bullerdiek J, Kazmierczak B. Assignment of GUCY1A3, a candidate gene for hypertension, to human chromosome bands 4q31.1-->q31.2 by in situ hybridization. Cytogenet Cell Genet. 2000;88:204-5 pubmed
  22. Siednienko J, Nowak J, Moynagh P, Gorczyca W. Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-?B activity. Cytokine. 2011;54:282-8 pubmed publisher
    ..These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway. ..
  23. Yao B, Xu Y, Wang J, Qiao Y, Zhang Y, Zhang X, et al. Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells. Cell Signal. 2016;28:1703-12 pubmed publisher
    ..Notably, TRIB2 was found to maintain the stability of guanylate cyclase 1 alpha 3 (GUCY1A3), a key component of HBP, by interacting GUCY1A3 and reducing its ubiquitination...
  24. Chauhan S, Jelen F, Sharina I, Martin E. The G-protein regulator LGN modulates the activity of the NO receptor soluble guanylate cyclase. Biochem J. 2012;446:445-53 pubmed publisher
    ..The interaction of sGC with these scaffolding proteins may expand the cross-talk between NO/cGMP signalling and other cellular pathways and tailor sGC function to specific tissues or signals. ..
  25. Lu X, Wang L, Lin X, Huang J, Charles Gu C, He M, et al. Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension. Hum Mol Genet. 2015;24:865-74 pubmed publisher
    ..8 (CASZ1, MOV10, FGF5, CYP17A1, SOX6, ATP2B1, ALDH2, and JAG1) at genome-wide significance, and 6 (FIGN, ULK4, GUCY1A3, HFE, TBX3-TBX5, and TBX3) at a suggestive level of P = 1.81 × 10(-3) to 5.16 × 10(-8)...
  26. Lu X, Wang L, Chen S, He L, Yang X, Shi Y, et al. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet. 2012;44:890-4 pubmed publisher
    ..These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1...
  27. Meurer S, Pioch S, Pabst T, Opitz N, Schmidt P, Beckhaus T, et al. Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteasomal degradation. Circ Res. 2009;105:33-41 pubmed publisher
    ..Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC. ..
  28. Schermuly R, Stasch J, Pullamsetti S, Middendorff R, Muller D, Schluter K, et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur Respir J. 2008;32:881-91 pubmed publisher
    ..Stimulation of soluble guanylate cyclase reversed right heart hypertrophy and structural lung vascular remodelling. Soluble guanylate cyclase may thus offer a new target for therapeutic intervention in pulmonary arterial hypertension. ..
  29. Wallace S, Guo D, Regalado E, Mellor Crummey L, Bamshad M, Nickerson D, et al. Disrupted nitric oxide signaling due to GUCY1A3 mutations increases risk for moyamoya disease, achalasia and hypertension. Clin Genet. 2016;90:351-60 pubmed publisher
    ..Homozygous mutations in GUCY1A3 have been reported as a cause of MMD and achalasia...
  30. Emdin C, Khera A, Klarin D, Natarajan P, Zekavat S, Nomura A, et al. Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling. Circulation. 2018;137:222-232 pubmed publisher
    ..nitric oxide signaling (Nitric Oxide Synthase 3 [NOS3] and Guanylate Cyclase 1, Soluble, Alpha 3 [GUCY1A3]) with a range of human phenotypes...
  31. Bhansali M, Shemshedini L. COP9 subunits 4 and 5 target soluble guanylyl cyclase ?1 and p53 in prostate cancer cells. Mol Endocrinol. 2014;28:834-45 pubmed publisher
  32. Krogh K, Wydeven N, Wickman K, Thayer S. HIV-1 protein Tat produces biphasic changes in NMDA-evoked increases in intracellular Ca2+ concentration via activation of Src kinase and nitric oxide signaling pathways. J Neurochem. 2014;130:642-56 pubmed publisher
    ..Adaptation may be a novel neuroprotective mechanism to prevent excessive Ca(2+) influx. Solid and dashed arrows represent direct and potentially indirect connections, respectively. ..
  33. Gao S, Hsieh C, Zhou J, Shemshedini L. Zinc Finger 280B regulates sGC?1 and p53 in prostate cancer cells. PLoS ONE. 2013;8:e78766 pubmed publisher
    ..Thus, by enhancing the expression of Mdm2, the uncharacterized 280B protein provides a novel mechanism of p53 suppression in prostate cancer. ..