Protein methylation is a post-translational modification process, in which proteins are modified by an addition of methyl groups by S-adenosylmethionine dependent methyltransferases, with S-adenosyl methionine (SAM) as the primary donor of methyl group. Methylation of proteins can occur on multiple amino acids on proteins, including arginine, lysine, histidine, etc. Methylation is mediated by methyltransferases, Methylation of lysine involves the addition of one to three methyl groups on the amino acid's ?-amine group, to form mono-, di- or tri-methyllysine. This modification often occurs in a conserved sequence motif on proteins. For example, two typical motifs are RGG box and RXR sequence. Depending on the site of residual methyl group attached to, there are two types of methylation: N-methylation and O-methylation. N-methylation is irreversible, whereas, O-methylation is potentially reversible.