a protein lysine methyltransferase that specifically trimethylates K9 of histone H3 (H3K9me3), a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Unlike SUV39H H3K9 methyltransferase, which functions mainly in heterochromatin regions such as pericentric heterochromatin, SETDB1 functions mainly in euchromatic regions, playing a central role in the silencing of euchromatic genes. H3K9me3 is coordinated with DNA methylation. Interacts with a variety of proteins, including transcription factors (ERG), histone deacetylases (HDAC1/2), DNA methyltransferases (DNMT3A/B) and transcriptional co-repressors (mSin3A/B, MBD1, KAP-1, the ATFa-associated modulator mAM). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. Contains Tudor and methyl-CpG-binding domains, which may coordinate binding to methylated histones and methylated DNA, respectively. Is targeted to histone H3 by TIF1B, a factor recruited by KRAB zinc-finger proteins. Recruited by DNMT3A to silenced promoters in cancer cells. May play a role in the pathogenesis of Huntington's disease, since levels of SETDB1 and H3K9me3 are both increased in diseased brains. Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily. Three isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Amino Acid Metabolism - lysine degradation; Methyltransferase; EC 184.108.40.206; Methyltransferase, protein lysine
Cellular Component: chromosome
Molecular Function: protein binding; DNA binding; zinc ion binding; histone-lysine N-methyltransferase activity
Biological Process: regulation of transcription, DNA-dependent; transcription, DNA-dependent; inner cell mass cell proliferation
Alt. Names/Synonyms: ERG-associated protein with a SET domain, ESET; ERG-associated protein with SET domain; ESET; H3-K9-HMTase 4; H3-K9-HMTase4; Histone H3-K9 methyltransferase 4; Histone-lysine N-methyltransferase SETDB1; histone-lysine N-methyltransferase, H3lysine-9 specific 4; KG1T; KIAA0067; KMT1E; Lysine N-methyltransferase 1E; SET domain bifurcated 1; SET domain, bifurcated 1; SETB1; SETDB1
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.