Chapter 14
Computational Prediction of Protein O-GlcNAc Modification
Cangzhi Jia and Yun Zuo
Abstract
Protein O-GlcNAcylation on serine and threonine residues is a significant posttranslational modification.
Experimental techniques can uncover only a small portion of O-GlcNAcylation sites. Several computational
algorithms have been proposed as necessary auxiliary tools to identify potential O-GlcNAcylation sites. This
chapter discusses the metrics and procedures used to assess prediction tools and surveys six computational
tools for the prediction of protein O-GlcNAcylation sites. Analyses of these tools using an independent test
dataset indicated the advantages and disadvantages of the six existing prediction methods. We also discuss
the challenges that may be faced while developing novel predictors in the future.
KeywordsO-GlcNAcylation, Prediction, Sequence information, Features
1 Introduction
O-linked N-acetylglucosamine (O-GlcNAc) was discovered in
early 1984 by the famous biochemist Gerald W. Hart [1].
O-GlcNAcylation on serine and threonine residues of proteins is
recognized as a significant extensive and dynamic posttranslational
modification that occurs in animals, plants, microorganisms, and
viruses. Protein O-GlcNAcylation is completed through the coop-
eration of O-GlcNAc transferase, which is responsible for the addi-
tion of O-GlcNAc, and O-GlcNAcase, which is also responsible for
removal of O-GlcNAc to and from the hydroxyl groups of serine
and threonine residues [2]. The chemical structure of O-GlcNAc
glycosylation is illustrated in Fig.1.
Recent studies have shown that protein O-GlcNAcylation is
involved in multiple cellular processes, such as transcription, trans-
lation, cell signal transduction, and cell stress response. Abnormal
O-GlcNAcylation can lead to diseases, such as cancer, diabetes, and
a variety of neurodegenerative diseases [3, 4]. As a result, research
of protein O-GlcNAcylation is attracting more and more attention.
Although experimental techniques to detect and accurately
localize protein O-GlcNAcylation sites have improved significantly
Tao Huang (ed.),Computational Systems Biology: Methods and Protocols, Methods in Molecular Biology, vol. 1754,
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