O-GlcNAc glycans in the mammalian extracellular environment

Extracellular O-GlcNAc is a unique post-translational modification that occurs in the epidermal growth factor-like (EGF) domain of the endoplasmic reticulum (ER) lumen. The EGF domain-specific O-GlcNAc transferase (EOGT), catalyzes the transfer of O-GlcNAc to serine/threonine residues of the C-terminal EGF domain. Thus, EOGT-dependent O-GlcNAc modifications are mainly found in selective proteins that are localized in the extracellular spaces or extracellular regions of membrane proteins. In mammals, O-GlcNAc glycans can be extended to oligosaccharide structures similar to other types of EGF domain-specific O-glycans. The in vivo importance of O-GlcNAc glycans in mammals has been demonstrated in a human congenital disease caused by EOGT mutations and is extensively supported by genetic deletion in mice. This article reviews the findings on the structure and biochemical mechanism of EOGT-catalyzed O-GlcNAc biosynthesis, modified proteins, and in vivo functions elucidated by recent research in mammals.