A heterodimeric protein (with α and β subunits) that catalyses the synthesis of the second messenger guanosine 3′,5′- cyclic monophosphate (cGMP) from GTP. The enzyme is the main receptor for nitric oxide (NO) and nitrovasodilator drugs which stimulate the production of cGMP. The soluble form is found in brain and has α1 (690 aa) and β1 (619 aa) subunits. The plasma membrane form of guanylate cyclase is an integral membrane protein with an extracellular receptor for peptide hormones, a transmembrane domain, a protein kinase-like domain, and a guanylate cyclase domain. Various isoforms are known, some being receptors for natriuretic peptides. Mutations in human photoreceptor guanylate cyclase 2D (1103 aa) cause some forms of Leber congenital amaurosis and a dominant form of cone–rod dystrophy. Guanylate cyclase-activating protein (GCAP1, 201 aa) is a calcium-binding protein of the calmodulin superfamily, expressed exclusively in photoreceptor inner segments, that stimulates synthesis of cGMP. Mutations in this cause cone dystrophy and may be responsible for other types of Leber amaurosis. Guanylin is GCAP2A, uroguanylin is GCAP2B.
Subjects: Medicine and Health — Chemistry.