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 2.1.1.43; Methyltransferase; Methyltransferase, protein lysine
Chromosomal Location of mouse Ortholog: 3|3 F2.1
Cellular Component:  chromosome; cytoplasm; intracellular membrane-bounded organelle; nucleoplasm; nucleus
Molecular Function:  chromatin binding; DNA binding; histone H3K9 methyltransferase activity; histone H3K9 trimethyltransferase activity; histone H3K9me2 methyltransferase activity; metal ion binding; methyltransferase activity; promoter-specific chromatin binding; protein binding; transferase activity; zinc ion binding
Biological Process:  bone development; chromatin organization; heterochromatin organization; histone H3-K9 methylation; histone lysine methylation; inner cell mass cell proliferation; methylation; negative regulation of gene expression; negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; negative regulation of transcription by RNA polymerase II; positive regulation of DNA methylation-dependent heterochromatin formation
Reference #:  O88974 (UniProtKB)
Alt. Names/Synonyms: AU022152; ERG-associated protein with SET domain; ESE; ESET; Histone-lysine N-methyltransferase SETDB1; Kiaa0067; KMT1E; MGC90670; mKIAA0067; OTTMUSP00000018599; OTTMUSP00000018601; SET domain bifurcated 1; SET domain ERG-associated histone methyltransferase; SET domain, bifurcated 1; SETB1; Setdb1
Gene Symbols: Setdb1
Molecular weight: 144,549 Da
Basal Isoelectric point: 5.71  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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SETDB1

Protein Structure Not Found.


Cross-references to other databases:  AlphaFold  |  STRING  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene