Soluble guanylate cyclase alpha-2 beta-1 heterodimer (sGC α2β1) (sGC α2β1)

Soluble guanylate cyclase (sGC) is a heme-containing enzyme that serves as the primary intracellular receptor for nitric oxide (NO), catalyzing the conversion of GTP to the second messenger cyclic guanosine monophosphate (cGMP) (UniProt P33402, Q02108). The α2β1 heterodimer is one of two functional isoforms of sGC, composed of the alpha-2 (GUCY1A2) and beta-1 (GUCY1B1) subunits, and is notably expressed in the brain, placenta, and spleen (PMID: 11459323). In the central nervous system, this isoform is often localized to the postsynaptic density, where it modulates neurotransmission and synaptic plasticity (PMID: 12855598). Dysregulation of the NO-sGC-cGMP pathway is a key factor in the pathogenesis of cardiovascular diseases, including pulmonary arterial hypertension and chronic heart failure (PubMed: 23824141). Pharmacological agents such as sGC stimulators (e.g., riociguat) and sGC activators (e.g., vericiguat) target the enzyme to restore cGMP signaling, promoting vasodilation and inhibiting pathological remodeling (FDA: Adempas, Verquvo). These therapies are critical for managing patients with impaired NO bioavailability or high oxidative stress, which can render the enzyme unresponsive to endogenous NO.

Other names

GUCY1A2/GUCY1B1Guanylate cyclase soluble subunit alpha-2/beta-1sGC alpha2beta1Guanylyl cyclase soluble alpha-2/beta-1

Soluble guanylate cyclase stimulator and activator