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The Neprilysin Family in Health and Disease

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Cellular Peptidases in Immune Functions and Diseases 2

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 477))

Abstract

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 enzymeshave 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 genomicsbased approach to understanding the functions of thisproteinase family is aided by the completion of the C. elegans and Drosophila genomes, both of which encode multiple copies of NEP-like enzymes.

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Authors and Affiliations

  1. School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

    Anthony J. Turner, Carolyn D. Brown, Julie A. Carson & Kay Barnes

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  1. Anthony J. Turner
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  2. Carolyn D. Brown
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  3. Julie A. Carson
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  4. Kay Barnes
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Editors and Affiliations

  1. Martin Luther University, Halle, Germany

    Jürgen Langner

  2. Otto von Guericke University, Magdeburg, Germany

    Siegfried Ansorge

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© 2002 Kluwer Academic Publishers

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Turner, A.J., Brown, C.D., Carson, J.A., Barnes, K. (2002). The Neprilysin Family in Health and Disease. In: Langner, J., Ansorge, S. (eds) Cellular Peptidases in Immune Functions and Diseases 2. Advances in Experimental Medicine and Biology, vol 477. Springer, Boston, MA. https://doi.org/10.1007/0-306-46826-3_25

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  • DOI: https://doi.org/10.1007/0-306-46826-3_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46383-9

  • Online ISBN: 978-0-306-46826-1

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