Arginine methylation at a glance.

Arginine methylation is a prevalent post-translational modification found on both nuclear and cytoplasmic proteins. The methylation of arginine residues is catalyzed by the protein arginine Nmethyltransferase (PRMT) family of enzymes. Proteins that are arginine methylated are involved in a number of different cellular processes, including transcriptional regulation, RNA metabolism and DNA damage repair (Bedford and Richard, 2005). Most PRMTs methylate glycineand arginine-rich patches (GAR motifs) within their substrates. The complexity of the methylarginine mark is enhanced by the ability of this residue to be methylated in three different ways on the guanidino group: monomethylated (MMA), symmetrically dimethylated (sDMA) and asymmetrically dimethylated (aDMA), each of which has potentially different functional consequences. Mammalian arginine methyltransferases There are three structurally defined types of S-adenosylmethionine (AdoMet)dependent methyltransferase (Katz et al., 2003). The largest class (Class I) has a common seven-stranded -sheet structure. The Class II enzymes are the SET lysine methyltransferases and Class III encompasses the membraneassociated methyltransferases. PRMT family members fall into Class I and harbor a set of four conserved sequence motifs (I, post-I, II, and III) and a THW loop (Katz et al., 2003). Motifs I, post-I and the THW loop form part of the AdoMet-binding pocket (Zhang et al., 2000). Ten mammalian PRMTs have been identified to date. Eight have been shown to catalyze the transfer of a methyl group from AdoMet to a guanidino nitrogen of arginine, generating Sadenosylhomocysteine (AdoHcy) and methylarginine. No activity has yet been demonstrated for PRMT2 and PRMT9.