Human neprilysin-2 (NEP2) and NEP display distinct subcellular localisations and substrate preferences.
Neprilysin-2 (NEP2) is a novel metallopeptidase homologous to neprilysin (NEP), an enzyme involved in regulation of neuropeptide signalling. NEP2 exists as two alternatively spliced isoforms, NEP2 and NEP2(Delta). In this study, we cloned and expressed both human isoforms. Human NEP2 exists as a membrane-bound and soluble enzyme, whereas human NEP2(Delta) exists as two membrane-bound glycoforms, localised to the ER and plasma membrane. Surprisingly, NEP2 substrate specificity and inhibitor binding was distinct from that of human NEP, suggesting that NEP and NEP2 play distinct physiological roles in humans, and human NEP2 differs markedly from its rodent homologues.
Proteolysis Research Group, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK. a.r.whyteside@leeds.ac.uk
Alison R
AR
Whyteside
Anthony J
AJ
Turner
D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000201:enzymology; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D006801:Humans; D015260:Neprilysin / Q000032:analysis* / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D013379:Substrate Specificity
D011480:Protease Inhibitors; D020033:Protein Isoforms; C436550:MMEL1 protein, human; D015260:Neprilysin