Tbio SETDB1 Histone-lysine N-methyltransferase SETDB1

Protein Summary

Description

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. Probably 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 (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). 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 (PubMed:27029610). This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

Uniprot Accession IDs

• Q15047
• A6NEW2
• Q5SZD8
• Q5SZD9
• Q5SZE0
• Q5SZE7
• Q96GM9

Gene Name

• SETDB1

Ensembl ID

• ENST00000271640
• ENSP00000271640
• ENSG00000143379
• ENST00000368962
• ENSP00000357958
• ENST00000368969
• ENSP00000357965

Symbol

• KIAA0067
• KMT1E
• ESET
• KG1T
• KMT1E
• TDRD21
• H3-K9-HMTase4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.97
ligand (protein) perturbation	0.96
histone modification site profile	0.87
hub protein	0.85
molecular function	0.79

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 214.57   (req: < 5)

Gene RIFs: 96   (req: <= 3)

Antibodies: 356   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 214.57   (req: >= 5)

Gene RIFs: 96   (req: > 3)

Antibodies: 356   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0