Identification and bioinformatic analysis of neprilysin and neprilysin-like metalloendopeptidases in Drosophila melanogaster

Abstract

The neprilysin (M13) family of metalloendopeptidases comprises highly conserved ectoenzymes that cleave and thereby inactivate many physiologically relevant peptides in the extracellular space. Impaired neprilysin activity is associated with numerous human diseases. Here, we present a comprehensive list and classification of M13 family members in Drosophila melanogaster. Seven Neprilysin (Nep) genes encode active peptidases, while 21 Neprilysin-like (Nepl) genes encode proteins predicted to be catalytically inactive. RNAseq data demonstrate that all 28 genes are expressed during development, often in a tissue-specific pattern. Most Nep proteins possess a transmembrane domain, whereas almost all Nepl proteins are predicted to be secreted.

Table 1. Genes encoding Drosophila melanogaster neprilysins and neprilysin-like metalloendopeptidases.

Symbol: symbol of the Drosophila gene in FlyBase; CG #: gene model annotation ID; Genomic location: chromosome scaffold and FlyBase-computed cytological location of the gene; Expression: heat-map representation of expression levels throughout development (yellow/red scale; embryos (E), larvae (L), prepupae (PP), pupae (P), adult males (M) and adult females (F)) and in adult tissues (green scale; brain/CNS (Br), fat body (Fb), heart (Ht), testis (Ts) and spermatheca (Sp)), where white represents undetectable expression; Motifs: presence of a signal peptide (SP) or a single transmembrane domain (TM) is indicated, together with the amino acid sequence (if present) of each of the four conserved sequence motifs required for catalytic activity; Refs: reference(s) identifying/characterizing the Drosophila gene/protein: 1) Bland et al., 2008, 2) Sitnik et al., 2014, 3) Meyer et al., 2011, 4) Thomas et al., 2005, 5) Bland et al., 2007, 6) Bland et al., 2009, 7) Meyer et al., 2009, 8) Panz et al., 2012, 9) Hallier et al., 2016, 10) Findlay et al., 2014, 11) Matsuoka et al., 2014, 12) Nfonsam et al., 2012, 13) Banerjee et al., 2021.