SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' []. It was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me). However, this conclusion was based on mass spectrometry data wherein mass shifts were inconsistent with a bona fide methylation event. In vitro, the protein-lysine methyltransferase activity is weak compared to the protein-histidine methyltransferase activity [].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.A review published in 2003 []divides allmethyltransferases into 5 classes based on the structure of their catalyticdomain (fold):class I: Rossmann-like alpha/betaclass II: TIM beta/α-barrel alpha/betaclass III: tetrapyrrole methylase alpha/betaclass IV: SPOUT alpha/beta class V: SET domain all betaA more recent paper []based on a study of the Saccharomyces cerevisiaemethyltransferome argues for four more folds:class VI: transmembrane all alpha class VII: DNA/RNA-binding 3-helical bundle all alphaclass VIII: SSo0622-like alpha betaclass IX: thymidylate synthetase alpha betaClass V proteins contain the SET domain usually flanked byother domains forming the so-called pre- and post-SET regions. Except themembers of the STD3 family which N-methylate histidine in beta-actin (EC2.1.1.85) [, ], enzymes belonging to this class N-methylatelysine in proteins. Most of them are histone methyltransferases (EC 2.1.1.43)like the histone H3-K9 methyltransferase dim-5 or the histoneH3-K4 methyltransferase SETD7 [, ]. Some others methylatethe large subunit of the enzyme ribulose-bisphosphate-carboxylase/oxygenase(RuBisCO) (EC 2.1.1.127) in plants; in these enzymes the SET domain isinterrupted by a novel domain []. Cytochrome c lysine N-methyltransferases(EC 2.1.1.59) do not possess a SET domain, or at least not a SET domaindetected by any of the detection methods; however they do display a SET-likeregion and for this reason they are also assigned to this class [].
This entry represents the SET domain found in SETD3 and related proteins.SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' []. It was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me). However, this conclusion was based on mass spectrometry data wherein mass shifts were inconsistent with a bona fide methylation event. In vitro, the protein-lysine methyltransferase activity is weak compared to the protein-histidine methyltransferase activity [].
