PROSITE documentation PDOC00430 [for PROSITE entry PS00458]

Natriuretic peptides receptors signature

Natriuretic peptides are hormones involved in the regulation of fluid and electrolyte homeostasis. These hormones stimulate the intracellular production of cyclic GMP as a second messenger.

Currently, three types of natriuretic peptide receptors are known [1,2]. Two express guanylate cyclase activity: GC-A (or ANP-A) which seems specific to atrial natriuretic peptide (ANP), and GC-B (or ANP-B) which seems to be stimulated more effectively by brain natriuretic peptide (BNP) than by ANP. The third receptor (ANP-C) is probably responsible for the clearance of ANP from the circulation and does not play a role in signal transduction.

GC-A and GC-B are plasma membrane-bound proteins that share the following topology: an N-terminal extracellular domain which acts as the ligand binding region, then a transmembrane domain followed by a large cytoplasmic C-terminal region that can be subdivided into two domains: a protein kinase-like domain (see <PDOC00100>) that appears important for proper signalling and a guanylate cyclase catalytic domain (see <PDOC00425>). The topology of ANP-C is different: like GC-A and -B it possesses an extracellular ligand-binding region and a transmembrane domain, but its cytoplasmic domain is very short.

We developed a pattern from the ligand-binding region of natriuretic peptide receptors based on a highly conserved region located in the N-terminal part of the domain.