The neprilysin family in health and disease.
The mammalian neprilysin (NEP) family comprises at least seven members: NEP itself, Kell blood group antigen (KELL), the endothelin-converting enzymes (ECE-1 and ECE-2), the enzyme PEX, associated with X-linked hypophosphataemia, "X-converting enzyme" (XCE) a CNS-expressed orphan peptidase and a soluble, secreted endopeptidase (SEP). These zinc metallopeptidases are all type II integral membrane proteins. Where identified, these enzymes have roles in the processing or metabolism of regulatory peptides and therefore represent potential therapeutic targets. A distinct feature of ECE-1 species is their existence as distinct isoforms differing in their N-terminal cytoplasmic tails. These tails play a role in enzyme targeting and turnover with di-leucine and tyrosine-based motifs affecting localization. Additional anchorage of these enzymes can also occur through palmitoylation. Bacterial homologues of the neprilysin family exist, for example the products of the pepO genes from L. lactis and S. parasanguis, and a recently described gene product of P. gingivalis which is an ECE-1 homologue that can catalyse the conversion of big endothelin to endothelin. A genomics based approach to understanding the functions of this proteinase family is aided by the completion of the C. elegans and Drosophila genomes, both of which encode multiple copies of NEP-like enzymes.
Turner
A J
AJ
School of Biochemistry and Molecular Biology, University of Leeds, U.K.
Brown
C D
CD
Carson
J A
JA
Barnes
K
K
D000215:Acylation; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000201:enzymology*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D007626:Kell Blood-Group System / Q000235:genetics / Q000502:physiology; D013294:Lactococcus lactis / Q000201:enzymology / Q000235:genetics; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000201:enzymology*; D015260:Neprilysin / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D009928:Organ Specificity; D010146:Pain / Q000201:enzymology*; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000235:genetics; D020033:Protein Isoforms / Q000502:physiology; D011499:Protein Processing, Post-Translational; D013045:Species Specificity; D013379:Substrate Specificity
D001426:Bacterial Proteins; D016232:Endothelins; D015801:Helminth Proteins; D019476:Insect Proteins; D007626:Kell Blood-Group System; D009363:Neoplasm Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C080385:oligopeptidase PepO; D015260:Neprilysin; C000606923:ECE1 protein, human; C000606924:ECE2 protein, human; D000072396:Endothelin-Converting Enzymes