Following the transfer of the N-glycan precursor to the acceptor protein, the three terminal glucose residues of the N-glycan are sequentially removed by glucosidases. This step facilitates protein folding in the endoplasmic reticulum (ER) through interactions with lectin chaperones (calnexin/calreticulin cycle) and also serves as a marker to divert misfolded glycoproteins to the ER-associated degradation (ERAD) pathway. If the glycoprotein is correctly folded, the middle alpha 1,2-linked mannose is removed by class I mannosidases. The glycoprotein is then transported to the Golgi where the N-glycan undergoes further processing. (Adapted from
FBrf0235108 and
FBrf0224862.)