In eukaryotic cells, such as human and animal cells, protein glycosylation primarily occurs in the secretory pathway, beginning in the endoplasmic reticulum (ER) and completed in the golgi apparatus.
The process begins with the synthesis and translation of a protein in the ER, where the initial stages of protein folding occur. Following translation, glycans are enzymatically attached to amino acid residues, predominantly asparagine (N-linked glycosylation) or serine and threonine residues (O-linked glycosylation). In the Golgi, glycosylated proteins undergo additional modifications, facilitated by various enzymes and protein chaperones which trim or elongate glycans. Although O-linked glycosylation can commence in the ER, it predominantly initiates in the Golgi apparatus after the completion of protein folding.
The compartmentalized nature of protein glycosylation gives rise to a wide range of glycoproteins with diverse structures, leading to unique glycan profiles that reflect distinct protein functions.