Human Gene SETDB1 (uc001evu.2) Description and Page Index
Description: Homo sapiens SET domain, bifurcated 1 (SETDB1), transcript variant 1, mRNA. RefSeq Summary (NM_001145415): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: D31891.1, SRR1803614.180801.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## Transcript (Including UTRs) Position: hg19 chr1:150,898,815-150,937,220 Size: 38,406 Total Exon Count: 22 Strand: + Coding Region Position: hg19 chr1:150,900,191-150,936,840 Size: 36,650 Coding Exon Count: 21
ID:SETB1_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase SETDB1; EC=22.214.171.124; AltName: Full=ERG-associated protein with SET domain; Short=ESET; AltName: Full=Histone H3-K9 methyltransferase 4; Short=H3-K9-HMTase 4; AltName: Full=Lysine N-methyltransferase 1E; AltName: Full=SET domain bifurcated 1; 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. 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. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBUNIT: Interacts with MBD1; interaction is abolished when MBD1 is sumoylated. Interacts with ATF7IP and ATF7IP2; the interaction with ATF7IP is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 'Lys-9'. During DNA replication, it is recruited by SETDB1 to form a S phase-specific complex that facilitates methylation of H3 'Lys-9' during replication-coupled chromatin assembly and is at least composed of the CAF-1 subunit CHAF1A, MBD1 and SETDB1. Interacts with ERG, TRIM28/TIF1B, CBX1, CBX5, CHD7, DNMT3A, HDAC1, HDAC2, NLK, PPARG, SIN3A, SIN3B, DNMT3B and SUMO2. Interacts with MPHOSPH8. INTERACTION: P31749:AKT1; NbExp=9; IntAct=EBI-79691, EBI-296087; Q9Y6K1:DNMT3A; NbExp=7; IntAct=EBI-79691, EBI-923653; SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associated with non-pericentromeric regions of chromatin. Excluded from nucleoli and islands of condensed chromatin. TISSUE SPECIFICITY: Widely expressed. High expression in testis. DOMAIN: The pre-SET, SET and post-SET domains are all required for methyltransferase activity. The 347-amino-acid insertion in the SET domain has no effect on the catalytic activity. DOMAIN: Isoform 2 lacks all domains required for histone methyltransferase activity. MISCELLANEOUS: Highly up-regulated in Huntington disease patients, suggesting that participates in the altered chromatin modulation and transcription dysfunction observed in Huntington disease. Its down-regulation has salubrious effects on patients, suggesting that it may be a promising treatment in Huntington disease patients. SIMILARITY: Belongs to the histone-lysine methyltransferase family. Suvar3-9 subfamily. SIMILARITY: Contains 1 MBD (methyl-CpG-binding) domain. SIMILARITY: Contains 1 post-SET domain. SIMILARITY: Contains 1 pre-SET domain. SIMILARITY: Contains 1 SET domain. SIMILARITY: Contains 2 Tudor domains. SEQUENCE CAUTION: Sequence=BAA06689.2; Type=Erroneous initiation; Sequence=CAI13325.1; Type=Erroneous gene model prediction; Sequence=CAI13326.1; Type=Erroneous gene model prediction;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): SETDB1 CDC HuGE Published Literature: SETDB1
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15047
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.