peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (PNgase, hPNGase, Peptide:N-glycanase, N-glycanase 1, NGLY1, PNG1)

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Function

specifically deglycosylates the denatured form of N-linked glycoproteins in cytoplasm & assists their proteasome-mediated degradation
cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan & the amide side chain of Asn, converting Asn to Asp
prefers proteins containing high-mannose over those bearing complex type oligosaccharides.
can recognize & deglycosylate misfolded proteins in the endoplasmic reticulum that are exported into the cytosol to be destroyed, while it has no activity toward native proteins
deglycosylation is prerequisite for subsequent proteasome- mediated degradation of some, but not all, misfolded glycoproteins
component of a complex required to couple retrotranslocation, ubiquitination & deglycosylation composed of NGLY1, SAKS1, AMFR, VCP & RAD23B
interacts with the proteasome components RAD23B & PSMC1
interacts directly with VCP
interacts with DERL1, bringing it close to the endoplasmic reticulum membrane
interacts with SAKS1
hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl)asparagine residue in which the glucosamine residue may be further glycosylated, to yield a (substituted) N-acetyl-beta-D-glucosaminylamine & a peptide containing an aspartate residue

Cofactor: Binds 1 Zn+2 per subunit (putative)

Inhibition:

inhibiteed by Z-VAD-fmk, a well-known caspase inhibitor, which inhibits enzyme activity through covalent binding of the carbohydrate to the single Cys-306 residue

in case of infection by cytomegaloviruses, it is not essential for degradation of MHC class 1 heavy chains