The functional diversity of protein lysine methylation

Large-scale characterization of post-translational modifications (PTMs), such as phosphorylation, acetylation and ubiquitination, has highlighted their importance in the regulation of a myriad of signaling events. While high-throughput technologies have tremendously helped cataloguing the proteins modified by these PTMs, the identification of lysine-methylated proteins, a PTM involving the transfer of one, two or three methyl groups to the ε-amine of a lysine side chain, has lagged behind. While the initial findings were focused on the methylation of histone proteins, several studies have recently identified novel non-histone lysine-methylated proteins. This review provides a compilation of all lysine methylation sites reported to date. We also present key examples showing the impact of lysine methylation and discuss the circuitries wired by this important PTM.