Reactome | Deglycosylation complex hydrolyses N-glycans from unfolded glycoproteins

Deglycosylation complex hydrolyses N-glycans from unfolded glycoproteins

Stable Identifier

R-HSA-8850594

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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Deglycosylation complex hydrolyses N-glycans from unfolded glycoproteins

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Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (NGLY1, aka PNGase) is a cytosolic peptide:N-glycanase which acts on N-glycoproteins generating free, unconjugated N-glycans and deglycosylated peptides in which the N-glycosylated asparagine residues are converted to aspartates. It is involved in the quality control system for misfolded glycoproteins exported to the cytosol that need to be targeted for degradation (Suzuki et al. 2016). NGLY1 is part of a complex that couples retrotranslocation, ubiquitination and deglycosylation. It is probably composed of NGLY1, UBX domain-containing protein 1 (UBXN1 aka SAKS1), E3 ubiquitin-protein ligase (AMFR), transitional endoplasmic reticulum ATPase (VCP), derlin-1 (DERL1), 26S protease regulatory subunit 4 (PSMC1) and UV excision repair protein RAD23 homolog B (RAD23B). NGLY1 interacts with the proteasome components RAD23B and PSMC1, directly with VCP and with DERL1, bringing it close to the endoplasmic reticulum membrane (Katiyar & Lennarz 2004, Song et al. 2005, McNeill et al. 2004, Ye et al. 2004, Katiyar et al. 2005).

Literature References

PubMed ID	Title	Journal	Year
16168377	Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase Song, BL, Sever, N, DeBose-Boyd, RA	Mol. Cell	2005
15362974	A novel UBA and UBX domain protein that binds polyubiquitin and VCP and is a substrate for SAPKs Cohen, P, Arthur, JS, Cuenda, A, Knebel, A, McNeill, H	Biochem. J.	2004
26611529	The cytoplasmic peptide:N-glycanase (NGLY1) - Structure, expression and cellular functions Huang, C, Fujihira, H, Suzuki, T	Gene	2016
15358861	A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins Li, G, Katiyar, S, Lennarz, WJ	Proc. Natl. Acad. Sci. U.S.A.	2004
16055502	The retrotranslocation protein Derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum Joshi, S, Katiyar, S, Lennarz, WJ	Mol. Biol. Cell	2005
15215856	A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol Shibata, Y, Ron, D, Yun, C, Rapoport, TA, Ye, Y	Nature	2004