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Review
. 2023 Aug 30;480(16):1241-1265.
doi: 10.1042/BCJ20220251.

A global view of the human post-translational modification landscape

Naoya Kitamura  1 , James J Galligan  1
Affiliations
Review

A global view of the human post-translational modification landscape

Naoya Kitamura et al. Biochem J. .

Abstract

Post-translational modifications (PTMs) provide a rapid response to stimuli, finely tuning metabolism and gene expression and maintain homeostasis. Advances in mass spectrometry over the past two decades have significantly expanded the list of known PTMs in biology and as instrumentation continues to improve, this list will surely grow. While many PTMs have been studied in detail (e.g. phosphorylation, acetylation), the vast majority lack defined mechanisms for their regulation and impact on cell fate. In this review, we will highlight the field of PTM research as it currently stands, discussing the mechanisms that dictate site specificity, analytical methods for their detection and study, and the chemical tools that can be leveraged to define PTM regulation. In addition, we will highlight the approaches needed to discover and validate novel PTMs. Lastly, this review will provide a starting point for those interested in PTM biology, providing a comprehensive list of PTMs and what is known regarding their regulation and metabolic origins.

Keywords: acetylation/deacetylation; acylation; glycation; mass spectrometry; methylglyoxal; post-translational modification.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1.
Figure 1.. A comprehensive view of the PTM landscape in the human proteome.
Figure 2.
Figure 2.. Analytical approaches for the study of PTMs.
Created with BioRender.com.
Figure 3.
Figure 3.. Lys acylations are structurally diverse yet display significant redundancy in modification sites.
Proteomic inventories were mined to reveal a striking overlap in modification sites. While many of these sites are surface-exposed, some display a high propensity to modification despite being stearically hindered (e.g. Lys343 on ENO1 and Cys152 on GAPDH). PTM sites were curated from [44,92,116–120,141–147]. ENO1 (PDB: 2SPN) and GAPDH (PDB:3GPD).
Figure 4.
Figure 4.. Hypothesized role for non-regulatory acylation sites on proteins.
Recent work has demonstrated the presence of non-regulatory acylation sites that can be taken back into acyl-CoA pools and redistributed to regulatory sites. We opine that this may serve as an additional metabolic feedback mechanism during periods of nutrient excess or demand. KDAC, lysine deacylase; ACSS, acyl-CoA synthetase short chain family member; KAT, Lys acytransferase. Created with BioRender.com.
See this image and copyright information in PMC

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