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

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 Structure: - belongs to the transglutaminase-like superfamily, PNGase family - contains 1 PAW domain - contains 1 PUB (PUG) domain, mediates the interaction with VCP Compartment: cytoplasm Alternative splicing: named isoforms=4 Miscellaneous: - in case of infection by cytomegaloviruses, it is not essential for degradation of MHC class 1 heavy chains

Properties

SIZE: MW = 74 kD entity length = 654 aa COMPARTMENT: cytoplasm MOTIF: PUB {30-91} Zn+2-binding site SITE: 250-250 Zn+2-binding site SITE: 253-253 Zn+2-binding site SITE: 283-283 Zn+2-binding site SITE: 286-286 cysteine residue {C309} histidine residue {H336} aspartate residue {D353} PAW {487-579}

Database Correlations

UniProt Q96IV0 Pfam PF01841

References

UniProt :accession Q96IV0