NGLY1
Domain
The PUB domain mediates the interaction with VCP.
Function
Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.
Involvement in disease
Congenital disorder of deglycosylation 1
CDDG1
An autosomal recessive multisystem disorder characterized by developmental delay, hypotonia, abnormal involuntary movements and alacrima or poor tear production. Other features include microcephaly, intractable seizures, abnormal eye movements and evidence of liver dysfunction, probably due to cytoplasmic accumulation of storage material in vacuoles.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the transglutaminase-like superfamily. PNGase family.
Cellular localization
- Cytoplasm
Alternative names
PNG1, NGLY1, Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase, PNGase, hPNGase, N-glycanase 1, Peptide:N-glycanase