This family of enzymes specifically methylate 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It plays an important role in transcriptional activation as a member of an RNA polymerase complex. It also binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences [].Methyltransferases (EC [intenz:2.1.1.-]) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [, , ]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM []. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [, , ]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [, , ]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
This entry represents the SET domain of SET and MYND domain-containing protein 3 (SMYD3). SMYD3 functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4 []. SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex []. It is overexpressed in colorectal, breast, prostate, and hepatocellular tumours, and has been implicated as an oncogene in human malignancies []. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers [].The SMYD family consists of five members including SMYD1/2/3/4/5. They contain two highly conserved structural and functional domains, the SET and MYND domains. The SET domain is involved in lysine methylation, while the MYND domain is involved in protein-protein interaction. They are essential in several mammalian developmental pathways [, , , ].
