| Post Translational Modifications | Degraded by the proteasome, shielded by interaction with ATF7IP. Monoubiquitinated at Lys-867 by E2 enzymes of the UBE2E family. The conjugated-Ub is protected from deubiquitination by the SET domain. Monoubiquitination at Lys-867 is required for catalytic activity, H3K9 methylation and endogenous retrovirus silencing. |
| Function | 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. |
| Protein Name | Histone-Lysine N-Methyltransferase Setdb1Erg-Associated Protein With Set DomainEsetHistone H3-K9 Methyltransferase 4H3-K9-Hmtase 4Lysine N-Methyltransferase 1eSet Domain Bifurcated 1 |
| Database Links | Reactome: R-HSA-3214841Reactome: R-HSA-9843940Reactome: R-HSA-9843970 |
| Cellular Localisation | NucleusCytoplasmChromosomeAssociated With Non-Pericentromeric Regions Of ChromatinExcluded From Nucleoli And Islands Of Condensed Chromatin |
| Alternative Protein Names | Histone-Lysine N-Methyltransferase Setdb1 proteinErg-Associated Protein With Set Domain proteinEset proteinHistone H3-K9 Methyltransferase 4 proteinH3-K9-Hmtase 4 proteinLysine N-Methyltransferase 1e proteinSet Domain Bifurcated 1 proteinSETDB1 proteinESET proteinKIAA0067 proteinKMT1E protein |
Information sourced from Uniprot.org
