Human neprilysin-2 (NEP2) and NEP display distinct subcellular localisations and substrate preferences

FEBS Lett. 2008 Jul 9;582(16):2382-6. doi: 10.1016/j.febslet.2008.05.046. Epub 2008 Jun 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Membrane / enzymology
  • Cricetinae
  • Cricetulus
  • Glycosylation
  • Humans
  • Neprilysin / analysis*
  • Neprilysin / metabolism*
  • Protease Inhibitors / pharmacology
  • Protein Isoforms / analysis
  • Protein Isoforms / metabolism
  • Substrate Specificity


  • Protease Inhibitors
  • Protein Isoforms
  • MMEL1 protein, human
  • Neprilysin