ERAD (ER-associated degradation) primarily involves:
ER-associated degradation provides clearance mechanism for terminally misfolded or orphan unassembled subunits that cannot be rescued by chaperones. Commitment step involves N-glycan mannose trimming as timer: ER mannosidase I and EDEM1-3, homologous to yeast Htm1, remove specific α1-2 mannose residues from high-mannose precursor Man9GlcNAc2 generating Man7-Man5 species exposing α1-6 mannose recognized as degradation signal. Trimmed glycans bound by MRH domains of degradation lectins OS-9 and XTP3-B that deliver clients to membrane-integrated ubiquitination apparatus comprising scaffold Sel1L
Ref: Smith et al., J Biol Chem 286: 2011, ERAD Involving Mannosidase Trimming.