Protein methylation was identified as a PTM in the 1980s; conversion of S-adenosyl-L-methionine (SAM) to S-adenosyl-L-homocysteine mediates transfer of methyl groups to a protein, a reaction catalyzed by a family of protein methyltransferases and subject to metabolic control . Methylated lysine exists in mono-, di-, and trimethylated forms. Methylated arginine exists in mono- and dimethylated forms [11, 12]. Trimethyl-arginine has not been identified to date. Methylation of arginine results in the addition of methyl groups to the guanidine nitrogens to form monomethyl-arginine and dimethyl- arginine. Symmetric and asymmetric dimethyl-arginines are both naturally occurring forms, resulting from the addition of two methyl groups to one or two guanidino nitrogen atoms, respectively. Although the extent to which dem- ethylation occurs has been debated, it is clearly accepted that lysine methylation status is enzyme mediated with the addition and removal of methylation catalyzed by lysine methyltransferases (KMTs) and demethylases (KDMs), two enzyme superfamilies. For arginine methylation, a key finding in this area is the identification of reversible arginine methylation of TRAF6 as a novel mechanism for dynamic regulation of innate immune pathways . Nonhistone lysine methylation also regulates signaling pathways including p53- and NFkB- mediated signaling .