The human O-GlcNAcome database and meta-analysis

Abstract

Over the past 35 years, ~1700 articles have characterized protein O-GlcNAcylation. Found in almost all living organisms, this post-translational modification of serine and threonine residues is highly conserved and key to biological processes. With half of the primary research articles using human models, the O-GlcNAcome recently reached a milestone of 5000 human proteins identified. Herein, we provide an extensive inventory of human O-GlcNAcylated proteins, their O-GlcNAc sites, identification methods, and corresponding references ( www.oglcnac.mcw.edu ). In the absence of a comprehensive online resource for O-GlcNAcylated proteins, this list serves as the only database of O-GlcNAcylated proteins. Based on the thorough analysis of the amino acid sequence surrounding 7002 O-GlcNAc sites, we progress toward a more robust semi-consensus sequence for O-GlcNAcylation. Moreover, we offer a comprehensive meta-analysis of human O-GlcNAcylated proteins for protein domains, cellular and tissue distribution, and pathways in health and diseases, reinforcing that O-GlcNAcylation is a master regulator of cell signaling, equal to the widely studied phosphorylation.

Fig. 1

The O-GlcNAc cycling. (a) The O-GlcNAc cycling in humans. (b) An O-GlcNAc in Brief portion highlights the features and actors of O-GlcNAcylation. HBP: Hexosamine Biosynthesis Pathway; OGT: O-GlcNAc Transferase; OGA: O-GlcNAcase; PTM: Post-Translational Modification; S/T: Serine/Threonine.

Fig. 2

Literature search for O-GlcNAcylated proteins identified over 5000 human O-GlcNAcylated proteins. (a) Method flowchart and exclusion criteria. (b) Study models found in the O-GlcNAc literature.

Fig. 3

O-GlcNAcylation semi-consensus sequence. (a) Serine and (b) Threonine O-GlcNAcylation semi-consensus sequences based on the 7002 human O-GlcNAcylation sites surrounding sequences.

Fig. 4

Cellular distribution of the O-GlcNAcome proteins. (a,b) Cellular localization of the human O-GlcNAcylated proteins (n = 4969). (a) The median and 95% Confidence intervals are represented. (b) Circle sizes and colors represent the median confidence score.

Fig. 5

Tissues distribution of the human O-GlcNAcome (a,b) Tissue distribution of the human O-GlcNAcylated proteins (n = 2052). (a) The median and 95% Confidence intervals are represented. (b) Circle sizes and colors represent the median confidence score.

Fig. 6

Protein domains and pathways enrichment of the human O-GlcNAcome. (a) Protein domain enrichment analysis of the human O-GlcNAcome. (b) Pathway enrichment analysis of the human O-GlcNAcome (n = 5059).