Actin-histidine N-methyltransferase SETD3 (IPR025785)

Short name: SETD3

Overlapping homologous superfamilies


Family relationships



SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' [PMID: 30526847]. 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 wherin 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 [PMID: 30526847].

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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [PMID: 16225687, PMID: 21858014, PMID: 12826405]. All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM [PMID: 7897657]. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids [PMID: 16225687, PMID: 21858014, PMID: 7897657]. Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [PMID: 16225687, PMID: 21858014, PMID: 12826405]. More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.

GO terms

Biological Process

GO:0030047 actin modification

Molecular Function

GO:0018064 protein-histidine 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