Protein glycosylation is a process whereby oligosaccharides covalently bind to specific amino acid residues on proteins in the form of glycosides. Protein glycosylation can be divided into four categories based on the connection method between the amino acid and the sugar: O-linked glycosylation, N-linked glycosylation, C-mannosylation, and glycosylphosphatidylinositol (GPI)-anchoring.
O-glycosylation predominantly occurs on serine or threonine residues proximal to proline, most proteins at the glycosylation site are beta conformers. O-linked oligosaccharides are formed by stepwise addition of monosaccharides to form oligosaccharides. So far, no specific protein sequence has been found as a glycosylation site. O-glycosylation reactions occur at two locations within the cell, one at the Golgi apparatus and the other in the nucleus or cytoplasm.
Glycosylation occurring in the Golgi apparatus initiates by adding N-acetylglucosamine, N-acetylgalactosamine, mannose, fucose, and other reducing ends to the hydroxyl group of serine and threonine. O-glycosylation of secreted proteins and membrane-bound proteins happens after N-glycosylation and protein folding, it occurs on the cis face of Golgi.
Glycosylation taking place in the nucleus and cytoplasm involves adding a single sugar, N-acetylglucosamine, to serine or threonine residues. The most common form of O-glycosylation in mammals is O-GalNAc glycosylation catalyzed by GalNAc transferase, which subsequently attaches Gal, GalNAc, or GlcNAc moieties.