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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:150,898,815-150,937,220)mRNA (may differ from genome)Protein (1291 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase SETDB1; EC=; 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

-  MalaCards Disease Associations
  MalaCards Gene Search: SETDB1
Diseases sorted by gene-association score: dracunculiasis (16), huntington disease (15), pleuropneumonia (11), hypoglycemic coma (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.90 RPKM in Testis
Total median expression: 363.45 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -61.70190-0.325 Picture PostScript Text
3' UTR -101.09380-0.266 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016177 - DNA-bd_integrase-typ
IPR025796 - Hist-Lys_N-MeTrfase_SETDB1
IPR001739 - Methyl_CpG_DNA-bd
IPR003616 - Post-SET_dom
IPR007728 - Pre-SET_dom
IPR003606 - Pre-SET_Zn-bd_sub
IPR001214 - SET_dom
IPR002999 - Tudor

Pfam Domains:
PF00856 - SET domain
PF01429 - Methyl-CpG binding domain
PF05033 - Pre-SET motif

SCOP Domains:
63748 - Tudor/PWWP/MBT
82199 - SET domain
54171 - DNA-binding domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q15047
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0008168 methyltransferase activity
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0018024 histone-lysine N-methyltransferase activity
GO:0046872 metal ion binding
GO:1990841 promoter-specific chromatin binding

Biological Process:
GO:0006325 chromatin organization
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0007265 Ras protein signal transduction
GO:0032259 methylation
GO:0033273 response to vitamin
GO:0034968 histone lysine methylation
GO:0045471 response to ethanol
GO:0090309 positive regulation of methylation-dependent chromatin silencing

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0043231 intracellular membrane-bounded organelle

-  Descriptions from all associated GenBank mRNAs
  LF383809 - JP 2014500723-A/191312: Polycomb-Associated Non-Coding RNAs.
AK302461 - Homo sapiens cDNA FLJ52896 complete cds, highly similar to Histone-lysine N-methyltransferase, H3lysine-9 specific 4 (EC
AK308335 - Homo sapiens cDNA, FLJ98283.
BC028671 - Homo sapiens SET domain, bifurcated 1, mRNA (cDNA clone MGC:16563 IMAGE:4098658), complete cds.
D31891 - Homo sapiens KIAA0067 mRNA.
BC009362 - Homo sapiens SET domain, bifurcated 1, mRNA (cDNA clone IMAGE:4301680), complete cds.
BC008738 - Homo sapiens cDNA clone IMAGE:3345759, with apparent retained intron.
JD408102 - Sequence 389126 from Patent EP1572962.
KJ900837 - Synthetic construct Homo sapiens clone ccsbBroadEn_10231 SETDB1 gene, encodes complete protein.
CU679323 - Synthetic construct Homo sapiens gateway clone IMAGE:100018215 5' read SETDB1 mRNA.
AB383733 - Synthetic construct DNA, clone: pF1KSDA0067, Homo sapiens SETDB1 gene for SET domain, bifurcated 1, complete cds, without stop codon, in Flexi system.
LF352519 - JP 2014500723-A/160022: Polycomb-Associated Non-Coding RNAs.
LF352518 - JP 2014500723-A/160021: Polycomb-Associated Non-Coding RNAs.
LF352517 - JP 2014500723-A/160020: Polycomb-Associated Non-Coding RNAs.
LF352514 - JP 2014500723-A/160017: Polycomb-Associated Non-Coding RNAs.
LF352513 - JP 2014500723-A/160016: Polycomb-Associated Non-Coding RNAs.
LF352512 - JP 2014500723-A/160015: Polycomb-Associated Non-Coding RNAs.
LF352506 - JP 2014500723-A/160009: Polycomb-Associated Non-Coding RNAs.
AK095075 - Homo sapiens cDNA FLJ37756 fis, clone BRHIP2023773, highly similar to Mus musculus ERG-associated protein ESET mRNA.
LF352505 - JP 2014500723-A/160008: Polycomb-Associated Non-Coding RNAs.
JD317600 - Sequence 298624 from Patent EP1572962.
JD402863 - Sequence 383887 from Patent EP1572962.
JD152122 - Sequence 133146 from Patent EP1572962.
JD146899 - Sequence 127923 from Patent EP1572962.
MA619386 - JP 2018138019-A/191312: Polycomb-Associated Non-Coding RNAs.
MA588096 - JP 2018138019-A/160022: Polycomb-Associated Non-Coding RNAs.
MA588095 - JP 2018138019-A/160021: Polycomb-Associated Non-Coding RNAs.
MA588094 - JP 2018138019-A/160020: Polycomb-Associated Non-Coding RNAs.
MA588091 - JP 2018138019-A/160017: Polycomb-Associated Non-Coding RNAs.
MA588090 - JP 2018138019-A/160016: Polycomb-Associated Non-Coding RNAs.
MA588089 - JP 2018138019-A/160015: Polycomb-Associated Non-Coding RNAs.
MA588083 - JP 2018138019-A/160009: Polycomb-Associated Non-Coding RNAs.
MA588082 - JP 2018138019-A/160008: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00310 - Lysine degradation

Reactome (by CSHL, EBI, and GO)

Protein Q15047 (Reactome details) participates in the following event(s):

R-HSA-5159250 ATF7IP binds SETDB1
R-HSA-3214841 PKMTs methylate histone lysines
R-HSA-3247509 Chromatin modifying enzymes
R-HSA-4839726 Chromatin organization

-  Other Names for This Gene
  Alternate Gene Symbols: A6NEW2, KIAA0067, KMT1E, NM_001145415, NP_001138887, Q15047, Q5SZD8, Q5SZD9, Q5SZE0, Q5SZE7, Q96GM9, SETB1_HUMAN
UCSC ID: uc001evu.2
RefSeq Accession: NM_001145415
Protein: Q15047 (aka SETB1_HUMAN or SETB_HUMAN)
CCDS: CCDS972.1, CCDS44217.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001145415.1
exon count: 22CDS single in 3' UTR: no RNA size: 4449
ORF size: 3876CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7923.00frame shift in genome: no % Coverage: 99.93
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.