InterPro domain: IPR044674

This entry represents a group of alpha-1,2-specific exomannosidases that are involved in endoplasmic reticulum-associated degradation (ERAD), including EDEM1/2/3 from humans, Mnl1 from yeasts and MNS4/5 from Arabidopsis. Mnl1 forms a complex with Pdi1 to process unfolded protein-bound Man8GlcNAc2 oligosaccharides to Man7GlcNAc2, promoting degradation in unfolded protein response [ 1 ]. In humans, mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1, while EDEM2 catalyses the first mannose trimming step from Man9GlcNAc2 [ 2 ]. EDEM1 has been shown to recognise and deliver misfolded proteins to the SEL1L-containing ERAD complex [ 3 ]. MNS4/5 function in the formation of unique N-glycan structures that are specifically recognized by components of the endoplasmic reticulum-associated degradation (ERAD) machinery, which leads to the degradation of misfolded glycoproteins [ 4 ].

1. A Complex of Htm1 and the Oxidoreductase Pdi1 Accelerates Degradation of Misfolded Glycoproteins. J Biol Chem 291, 12195-207
2. EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step. J. Cell Biol. 206, 347-56
3. EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex. Mol Cell 34, 627-33
4. Arabidopsis Class I α-Mannosidases MNS4 and MNS5 Are Involved in Endoplasmic Reticulum-Associated Degradation of Misfolded Glycoproteins. Plant Cell 26, 1712-1728