XB-FEAT-484049

nppa

This is the community wiki page for the gene nppa please feel free to add any information that is relevant to this gene that is not already captured elsewhere in Xenbase.

gene/protein function

Source: Devotta et al 2023: https://doi.org/10.7554/eLife.84036

Natriuretic peptides constitute a family of three structurally related but genetically distinct paracrine factors, A-type, B-type, and C-type natriuretic peptides, also known as Nppa, Nppb, and Nppc. They mediate their activity by binding three single-pass transmembrane receptors Npr1, Npr2, and Npr3. Nppa and Nppb have a higher affinity for Npr1, while Nppc binds more specifically to Npr2. All three ligands have a similar affinity for Npr3 (Suga et al., 1992). A fourth ligand, Osteocrin/musclin (Ostn) was originally identified in a screen for secreted signaling peptides in bone (Thomas et al., 2003) and skeletal muscle (Nishizawa et al., 2004). Ostn binds Npr3 specifically and with high affinity, competing with other ligands for binding (Kita et al., 2009; Moffatt and Thomas, 2009). Npr1 and Npr2 are guanylyl cyclase receptors that produce cGMP upon ligand-mediated activation, which in turn activates cGMP-dependent protein kinase G (PKG) and inhibits the activity of the cyclic nucleotide-degrading enzyme, phophodiesterase 3 (PDE3). In contrast, Npr3 lacks guanylyl cyclase activity and is primarily acting as a clearance receptor to regulate local concentrations of natriuretic peptides through receptor-mediated internalization and ligand degradation (Nussenzveig et al., 1990; Potter, 2011). In addition, the cytoplasmic tail of Npr3 possesses a Gi activator sequences that inhibits adenylyl cyclase (Anand-Srivastava et al., 1996; Murthy and Makhlouf, 1999). Natriuretic peptides have been implicated in a broad range of physiological processes, regulating blood volume and pressure, ventricular hypertrophy, fat metabolism, and long bone growth (Potter et al., 2006), however very little is known on its role during early embryonic development.