Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX.
Mammalian cell-surface peptidases participate in the postsecretory processing and metabolism of neuropeptides and peptide hormones. Neutral endopeptidase-24.11 (NEP) is the prototype of a family of zinc metallopeptidases that also includes the endothelin-converting enzymes (ECE) and which are structurally related to the bacterial enzymes thermolysin and lactococcal endopeptidase. Two other mammalian gene products exhibit strong homology with NEP: the erythrocyte cell-surface antigen, KELL; and the putative product of the PEX gene, which has been associated with X-linked hypophosphatemic rickets. No enzymic activity has yet been attributed to KELL and PEX proteins, and they remain peptidases in search of a substrate. A wide range of biologically active peptide substrates has been described for NEP, of which the enkephalins and the atrial natriuretic peptide family have assumed greatest significance. Endothelin-converting enzyme catalyses the final step in the biosynthesis of the vasoconstrictor peptide, endothelin (ET). Like NEP, it is a type II integral membrane protein, but is expressed predominantly in endothelial cells. Isoforms of ECE (ECE-1alpha, ECE-1beta, and ECE-2) exist that differ in a number of characteristics. In particular, ECE-1, through the paracrine effects of ET-1, may contribute to the proliferation of smooth muscle after angioplasty and to the development of human atherosclerosis. Inhibitors of ECE and NEP may have important therapeutic applications in cardiovascular and renal medicine.
Turner
A J
AJ
Department of Biochemistry and Molecular Biology, University of Leeds, U.K.
Tanzawa
K
K
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000502:physiology; D001798:Blood Proteins / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology*; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008666:Metalloendopeptidases / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015260:Neprilysin / Q000502:physiology; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D011506:Proteins / Q000502:physiology
D000954:Antigens, Surface; D001798:Blood Proteins; D008565:Membrane Proteins; D011506:Proteins; C041106:kell-active proteins; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human; C506232:Phex protein, mouse; D015260:Neprilysin; C000606923:ECE1 protein, human; C000606924:ECE2 protein, human; C000606925:Ece1 protein, mouse; C000606926:Ece2 protein, mouse; D000072396:Endothelin-Converting Enzymes