SETDB1 Histone methyltransferase that specifically trimethylates '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. 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. Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1. SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells. Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway. Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily. Widely expressed. High expression in testis. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Amino Acid Metabolism - lysine degradation; EC; Methyltransferase; Methyltransferase, protein lysine
Chromosomal Location of human Ortholog: 1q21.3
Cellular Component:  chromosome; cytoplasm; intracellular membrane-bounded organelle; nucleoplasm; nucleus
Molecular Function:  chromatin binding; DNA binding; histone H3K9 methyltransferase activity; histone lysine N-methyltransferase activity; promoter-specific chromatin binding; protein binding; zinc ion binding
Biological Process:  heterochromatin organization; histone H3-K9 methylation; negative regulation of gene expression; negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; positive regulation of DNA methylation-dependent heterochromatin formation; Ras protein signal transduction
Reference #:  Q15047 (UniProtKB)
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 histone lysine methyltransferase 1; SET domain, bifurcated 1; SETB1; SETDB1; TDRD21; tudor domain containing 21
Gene Symbols: SETDB1
Molecular weight: 143,157 Da
Basal Isoelectric point: 5.74  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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