Alternative titles; symbols
HGNC Approved Gene Symbol: GUCY1A2
Cytogenetic location: 11q22.3 Genomic coordinates (GRCh38): 11:106,674,019-107,018,476 (from NCBI)
Soluble guanylyl (or guanylate) cyclases are heterodimeric enzymes consisting of an alpha subunit, such as alpha-2 (GUCY1A2), and a beta subunit, typically beta-1 (GUCY1B3; 139397), which are activated by nitric oxide (NO) and which catalyze conversion of GTP to 3-prime, 5-prime-cyclic GMP and pyrophosphate (Harteneck et al., 1991).
Harteneck et al. (1991) described the cloning of a gene for the alpha-2 subunit of soluble guanylyl cyclase. The cDNA encodes a predicted 732-amino acid protein that has regions of high similarity to the alpha-1 (GUCY1A3; 139396) sequence.
Harteneck et al. (1991) found that, as with alpha-1, coexpression of alpha-2 with beta-1 in transfected COS cells resulted in guanylyl cyclase activity.
Russwurm and Koesling (2002) reviewed the 2 isoforms of the heterodimeric NO-sensitive guanylyl cyclase (NOGC), alpha-1/beta-1 and alpha-2/beta-1. They noted that NOGC had been considered a soluble enzyme, but evidence that the alpha-2 subunit of the alpha-2/beta-1 isoform interacts with the PDZ domain of PSD95 (DLG4; 602887) suggests that the alpha-2 subunit directs a membrane association of this isoform. The interaction with PSD95 locates the alpha-2/beta-1 isoform in close proximity to the NO-generating NO synthase (NOS1; 163731), thereby enabling the NO sensor to respond to locally raised NO concentrations.
Using quantitative real-time PCR and Western blot analysis to examine NOGC expression in mouse, Mergia et al. (2003) found that highest expression of the alpha-2/beta-1 isoform was in brain, with significant expression in lung and lower expression in all other tissues examined. Levels of the alpha-1/beta-1 and alpha-2/beta-1 isoforms were comparable in brain, but alpha-1/beta-1 was the predominant isoform in all other tissues examined. Overall, lung had the highest amount of NOGC content. Mergia et al. (2003) proposed that the alpha-2/beta-1 isoform may have a role in synaptic transmission.
Yu et al. (1996) mapped the GUCY1A2 gene to chromosome 11q21-q22 by fluorescence in situ hybridization.
Harteneck, C., Wedel, B., Koesling, D., Malkewitz, J., Bohme, E., Schultz, G. Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase. Interchangeability of the alpha-subunits of the enzyme. FEBS Lett. 292: 217-222, 1991. [PubMed: 1683630] [Full Text: https://doi.org/10.1016/0014-5793(91)80871-y]
Mergia, E., Russwurm, M., Zoidl, G., Koesling, D. Major occurrence of the new alpha-2/beta-1 isoform of NO-sensitive guanylyl cyclase in brain. Cell. Signal. 15: 189-195, 2003. [PubMed: 12464390] [Full Text: https://doi.org/10.1016/s0898-6568(02)00078-5]
Russwurm, M., Koesling, D. Isoforms of NO-sensitive guanylyl cyclase. Molec. Cell. Biochem. 230: 159-164, 2002. [PubMed: 11952091]
Yu, F., Warburton, D., Wellington, S., Danziger, R. S. Assignment of GUCIA2, the gene coding for the alpha-2 subunit of soluble guanylyl cyclase, to position 11q21-q22 on human chromosome 11. Genomics 33: 334-336, 1996. [PubMed: 8660992] [Full Text: https://doi.org/10.1006/geno.1996.0208]