Class V SAM-dependent methyltransferases (IPR016858)

Short name: Hist_H4-K20_MeTrfase

Overlapping homologous superfamilies


Family relationships



Methyltransferases (EC 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 nitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. Methyltransferases are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [PMID: 16225687, PMID: 12826405, PMID: 21858014]. More than 230 different enzymatic reactions of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor [E1]. A review published in 2003 [PMID: 12826405] divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold):

  • class I: Rossmann-like alpha/beta
  • class II: TIM beta/alpha-barrel alpha/beta
  • class III: tetrapyrrole methylase alpha/beta
  • class IV: SPOUT alpha/beta
  • class V: SET domain all beta

    A more recent paper [PMID: 21858014] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds:

  • class VI: transmembrane all alpha
  • class VII: DNA/RNA-binding 3-helical bundle all alpha
  • class VIII: SSo0622-like alpha+beta
  • class IX: thymidylate synthetase alpha+beta

This entry represents the class V proteins, which contain the SET domain usually flanked by other domains forming the so-called pre- and post-SET regions. The enzymes belonging to this class all N-methylate lysine in proteins. Most of them are histone methyltransferases (EC like the histone H3-K9 methyltransferase dim-5 or the histone H3-K4 methyltransferase SETD7 [PMID: 21858014, PMID: 12372294]. Some others methylate the large subunit of the enzyme ribulose-bisphosphate-carboxylase/oxygenase (RuBisCO) (EC in plants; in these enzymes the SET domain is interrupted by a novel domain [PMID: 12372294]. Cytochrome c lysine N-methyltransferases (EC do not possess a SET domain, or at least not a SET domain detected by any of the detection methods; however they do display a SET-like region and for this reason they are also assigned to this class [PMID: 17327221].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0018024 histone-lysine N-methyltransferase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles