biostudies-literatureHonda ANational Institute for Physiological SciencesJapan Agency for Medical Research and DevelopmentNational Institutes of Natural SciencesRIKENKagoshima UniversityJapan Society for the Promotion of Science110906https://www.ebi.ac.uk/biostudies/studies/S-EPMC12753239biostudies-literatureUnknown301(12)Peptide:N-glycanase (PNGase) is a deglycosylating enzyme acting on asparagine(N)-linked glycans on glycoproteins. It is well established that fish possesses two PNGases with distinct properties. One is a cytosolic PNGase (NGLY1 in humans), active at neutral pH and widely conserved among eukaryotes. The other is called acid PNGase and is found in fish embryos; it is active at acidic pH and is believed to be of lysosomal origin. The gene encoding the acid PNGase has not been identified in animals, and its evolutionary distribution has remained unknown. In this study, we identified the gene encoding the acid PNGase, which we named Ngly2, in zebrafish (Danio rerio). Interestingly, zebrafish Ngly2 was found to have structural similarity with bacterial PNGase (PNGase F) and indeed appeared to shThe Journal of biological chemistryStructural characterization of zebrafish Ngly2, an ovary-enriched acid PNGase required for egg-free glycan production.PMC1275323924NIPS20222K14950Honda AMatsuo IIshii NSuzuki THirayama HUeki MMurata KKamada KSeino JBurton-Smith RNFujihira HShiraki TfalseStructural characterization of zebrafish Ngly2, an ovary-enriched acid PNGase required for egg-free glycan production.Peptide:N-glycanase (PNGase) is a deglycosylating enzyme acting on asparagine(N)-linked glycans on glycoproteins. It is well established that fish possesses two PNGases with distinct properties. One is a cytosolic PNGase (NGLY1 in humans), active at neutral pH and widely conserved among eukaryotes. The other is called acid PNGase and is found in fish embryos; it is active at acidic pH and is believed to be of lysosomal origin. The gene encoding the acid PNGase has not been identified in animals, and its evolutionary distribution has remained unknown. In this study, we identified the gene encoding the acid PNGase, which we named Ngly2, in zebrafish (Danio rerio). Interestingly, zebrafish Ngly2 was found to have structural similarity with bacterial PNGase (PNGase F) and indeed appeared to sh2025-01-01T00:00:00Z2025 Dec2026-07-05T03:17:23.251Z2026-07-05T03:11:30.352ZS-EPMC127532394120312210.1016/j.jbc.2025.110906