Family

Histone-lysine N-methyltransferase SETDB1 (IPR025796)

Short name: Hist-Lys_N-MeTrfase_SETDB1

Family relationships

None.

Description

SETDB1 is a member of the histone-lysine N-methyltransferase Suvar3-9 subfamily. Members of this subfamily trimethylate 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones [PMID: 12869583]. This enzyme mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. It probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation [PMID: 14536086]. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 [PMID: 15327775]. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins [PMID: 17952062].

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.

Contributing signatures

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