Demystifying the O-GlcNAc Code: A Systems View

, murine, and human), prokaryotes, and some viruses. We evaluate features (e.g., structural properties and sequence motifs) of O-GlcNAc modification on proteins across species. Given that O-GlcNAcylation functions in a species-, tissue-/cell-, protein-, and site-specific manner, we discuss the functional roles of O-GlcNAcylation on human proteins. We focus particularly on several classes of relatively well-characterized human proteins (including transcription factors, protein kinases, protein phosphatases, and E3 ubiquitin-ligases), with representative O-GlcNAc site-specific functions presented. We hope the systems view of the great endeavor in the past 35 years will help demystify the O-GlcNAc code and lead to more fascinating studies in the years to come.