A Comparative Analysis and Review of lysyl Residues Affected by Posttranslational Modifications

Post-translational modification is the most common mechanism of regulating protein function. Ifphosphorylation is considered a key event in many signal transduction pathways, other modifications must beconsidered as well. In particular the side chain of lysine residues is a target of different modifications; notablyacetylation, methylation, ubiquitylation, sumoylation, neddylation, etc. Mass spectrometry approaches combininghighly sensitive instruments and specific enrichment strategies have enabled the identification of modifiedsites on a large scale. Here we make a comparative analysis of the most representative lysine modifications(ubiquitylation, acetylation, sumoylation and methylation) identified in the human proteome. This review focuses onconserved amino acids, secondary structures preference, subcellular localization of modified proteins, and signaling pathwayswhere these modifications are implicated. We discuss specific differences and similarities between these modifications,characteristics of the crosstalk among lysine post translational modifications, and single nucleotide polymorphismsthat could influence lysine post-translational modifications in humans.