Soluble guanylate cyclase subunit alpha-2

Soluble guanylate cyclase subunit alpha-2 (often abbreviated as sGC α2, gene symbol GUCY1A2) is one of the alpha subunits of soluble guanylate cyclase, a heterodimeric enzyme composed of alpha (α1 or α2) and beta (β1) chains[2][3][4][6][8]. sGC functions primarily as the intracellular receptor for nitric oxide (NO) and plays a critical role in cardiovascular signaling. Upon NO binding to the heme group on the β1 subunit, a conformational change is triggered which activates the catalytic domain of the enzyme, facilitating the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). This cGMP acts as a secondary messenger regulating processes like vasodilation, inhibition of platelet aggregation, and smooth muscle relaxation[2][5][6][7]. The α2 subunit is less abundant than α1 but can substitute in heterodimers, providing redundancy and meeting smooth muscle relaxation needs when α1 is absent[2]. Soluble guanylate cyclase is a validated drug target for conditions involving NO-cGMP signaling, particularly cardiovascular diseases, where sGC stimulators and activators—including riociguat, vericiguat, cinaciguat, and YC-1—are used therapeutically to enhance cGMP production and promote vasodilation[5][6]. Certain isoforms of the alpha-2 subunit may act as negative regulators by forming non-functional heterodimers with beta subunits[4][8].

Other names

GUCY1A2sGC alpha-2GCYA2guanylate cyclase soluble subunit alpha-2

Stimulates cGMP production by activating the catalytic domain (riociguat/vericiguat/YC-1), Allosteric activation or direct stimulation of oxidized/heme-free sGC (cinaciguat)