Soluble guanylate cyclase alpha-2 beta-1 (sGC2)

Soluble guanylate cyclase alpha-2 beta-1 (sGC2) is a heterodimeric enzyme that serves as the primary intracellular receptor for nitric oxide (NO) (PMID: 15102851). It consists of an alpha-2 subunit (GUCY1A2) and a beta-1 subunit (GUCY1B1), which together catalyze the conversion of guanosine triphosphate (GTP) to the second messenger cyclic guanosine monophosphate (cGMP) (UniProt P33402, Q02108). While the alpha-1 beta-1 isoform (sGC1) is ubiquitously expressed and dominant in the vasculature, the alpha-2 beta-1 isoform is predominantly localized in the central nervous system, particularly in the striatum and hippocampus, where it regulates synaptic plasticity and neurotransmission (PMID: 12810621). In the cardiovascular system, sGC-mediated cGMP production promotes vasodilation, inhibits platelet aggregation, and prevents pathological remodeling (PMID: 28655815). Dysregulation of the sGC/cGMP pathway is implicated in various conditions, including pulmonary hypertension, heart failure, and potentially neurodegenerative disorders. Pharmacological targeting of sGC involves stimulators like riociguat, which enhance the enzyme's sensitivity to NO, and activators like cinaciguat, which can activate the enzyme even when the essential heme group is oxidized or missing (FDA Label: Adempas). These therapies are primarily used to treat pulmonary arterial hypertension and chronic heart failure by restoring impaired cGMP signaling (FDA Label: Verquvo).

Other names

Soluble guanylate cyclase GC-2sGC alpha-2 beta-1GUCY1A2/GUCY1B1 complexGuanylate cyclase soluble subunit alpha-2sGC2

Soluble guanylate cyclase stimulator; Soluble guanylate cyclase activator