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 d... See more...

Aliases for SETDB1 Gene

Aliases for SETDB1 Gene

  • SET Domain Bifurcated Histone Lysine Methyltransferase 1 2 3 5
  • SET Domain Bifurcated 1 2 3 4
  • Histone-Lysine N-Methyltransferase SETDB1 3 4
  • Histone H3-K9 Methyltransferase 4 3 4
  • Lysine N-Methyltransferase 1E 3 4
  • Tudor Domain Containing 21 2 3
  • KMT1E 3 4
  • ESET 3 4
  • Histone-Lysine N-Methyltransferase, H3lysine-9 Specific 4 3
  • ERG-Associated Protein With A SET Domain, ESET 3
  • ERG-Associated Protein With SET Domain 4
  • SET Domain, Bifurcated 1 2
  • H3-K9-HMTase 4 4
  • H3-K9-HMTase4 3
  • EC 2.1.1.43 52
  • EC 2.1.1.- 4
  • KIAA0067 4
  • TDRD21 3
  • KG1T 3

External Ids for SETDB1 Gene

Previous GeneCards Identifiers for SETDB1 Gene

  • GC01P148740
  • GC01P146646
  • GC01P147673
  • GC01P148115
  • GC01P147711
  • GC01P149165
  • GC01P150898
  • GC01P122275

Summaries for SETDB1 Gene

Entrez Gene Summary for SETDB1 Gene

  • 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]

GeneCards Summary for SETDB1 Gene

SETDB1 (SET Domain Bifurcated Histone Lysine Methyltransferase 1) is a Protein Coding gene. Diseases associated with SETDB1 include Huntington Disease and Prostate Squamous Cell Carcinoma. Among its related pathways are Signaling pathways regulating pluripotency of stem cells and PKMTs methylate histone lysines. Gene Ontology (GO) annotations related to this gene include histone-lysine N-methyltransferase activity. An important paralog of this gene is KMT2C.

UniProtKB/Swiss-Prot Summary for SETDB1 Gene

  • 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 (PubMed:12869583, PubMed:17952062). 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 (PubMed:27732843, PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086, PubMed:15327775). 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). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). 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).

Gene Wiki entry for SETDB1 Gene

Additional gene information for SETDB1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SETDB1 Gene

Genomics for SETDB1 Gene

GeneHancer (GH) Regulatory Elements for SETDB1 Gene

Promoters and enhancers for SETDB1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SETDB1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SETDB1

Top Transcription factor binding sites by QIAGEN in the SETDB1 gene promoter:
  • ATF6
  • Cdc5
  • Lmo2
  • Sp1

Genomic Locations for SETDB1 Gene

Genomic Locations for SETDB1 Gene
chr1:150,926,263-150,964,901
(GRCh38/hg38)
Size:
38,639 bases
Orientation:
Plus strand
chr1:150,898,739-150,937,220
(GRCh37/hg19)
Size:
38,482 bases
Orientation:
Plus strand

Genomic View for SETDB1 Gene

Genes around SETDB1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SETDB1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SETDB1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SETDB1 Gene

Proteins for SETDB1 Gene

  • Protein details for SETDB1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15047-SETB1_HUMAN
    Recommended name:
    Histone-lysine N-methyltransferase SETDB1
    Protein Accession:
    Q15047
    Secondary Accessions:
    • A6NEW2
    • Q5SZD8
    • Q5SZD9
    • Q5SZE0
    • Q5SZE7
    • Q96GM9

    Protein attributes for SETDB1 Gene

    Size:
    1291 amino acids
    Molecular mass:
    143157 Da
    Quaternary structure:
    • Part of a complex containing at least CDYL, REST, WIZ, SETDB1, EHMT1 and EHMT2 (PubMed:19061646). 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 (PubMed:15327775). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306). Interacts with TRIM28/TIF1B (PubMed:11959841). Interacts with ATF7IP and ATF7IP2; the interaction with ATF7IP protects SETDB1 from proteasomal degradation and is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 'Lys-9' (PubMed:14536086, PubMed:15691849). Interacts with MBD1; interaction is abolished when MBD1 is sumoylated (PubMed:15327775, PubMed:17066076). Interacts with CBX1 and CBX5 (PubMed:15899859). Interacts with DNMT3A and DNMT3B (PubMed:16682412). Interacts with SUMO2. Interacts with CHD7, NLK1 and PPARG (PubMed:17952062). Interacts with MPHOSPH8 (PubMed:20871592). Interacts with ERG (By similarity). Interacts with HDAC1, HDAC2, SIN3A and SIN3B (By similarity). Interacts with ATRX. Forms a complex with ATRX, TRIM28 and ZNF274 (PubMed:27029610). Interacts with RESF1 (By similarity). Interacts with ZNF638 (PubMed:30487602).
    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.
    SequenceCaution:
    • Sequence=BAA06689.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SETDB1 Gene

    Alternative splice isoforms for SETDB1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SETDB1 Gene

Selected DME Specific Peptides for SETDB1 Gene

Q15047:
  • YPNRPMVLLK
  • EWIYRGS
  • DKSKCAC
  • FRRMTARRR
  • AGTELTWDYNYEVGSVEGK
  • FLEMFCLDPYVLVDR
  • LGKKRTKTWH
  • YKDGNQVWLYAG
  • VAYSKERIP
  • NRLVQHGLQVRLQLFKTQNKGWGIR
  • LSCVNEID
  • NHSCSPN
  • LPTGVYECN

Post-translational modifications for SETDB1 Gene

  • Degraded by the proteasome, shielded by interaction with ATF7IP.
  • Ubiquitination at Lys59 and Lys597
  • Modification sites at PhosphoSitePlus

Domains & Families for SETDB1 Gene

Gene Families for SETDB1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for SETDB1 Gene

Blocks:
  • Tudor domain
  • Nuclear protein SET
  • SET-related region
  • Methyl-CpG binding
  • Nuclear protein Zn2+-binding
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for SETDB1 Gene

GenScript: Design optimal peptide antigens:
  • SET domain, bifurcated 1 (B0QZE7_HUMAN)
  • cDNA FLJ52896, highly similar to Histone-lysine N-methyltransferase, H3lysine-9 specific 4 (EC 2.1.1.43) (B4DYJ0_HUMAN)
  • SET domain bifurcated 1 (SETB1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q15047

UniProtKB/Swiss-Prot:

SETB1_HUMAN :
  • 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.
  • Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.
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.
  • Isoform 2 lacks all domains required for histone methyltransferase activity.
  • In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.
Family:
  • Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.
genes like me logo Genes that share domains with SETDB1: view

Function for SETDB1 Gene

Molecular function for SETDB1 Gene

UniProtKB/Swiss-Prot 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 (PubMed:12869583, PubMed:17952062). 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 (PubMed:27732843, PubMed:14536086). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086, PubMed:15327775). 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). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). 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).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:60288, Rhea:RHEA-COMP:15538, Rhea:RHEA-COMP:15541, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961, ChEBI:CHEBI:61976; Evidence={ECO:0000255 PROSITE-ProRule:PRU00906, ECO:0000269 PubMed:14536086}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60289; Evidence=. ;.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.78 uM for S-adenosyl-L-methionine {ECO:0000269 PubMed:14536086};
GENATLAS Biochemistry:
protein with an unusual bifurcated SET domain protein 1

Enzyme Numbers (IUBMB) for SETDB1 Gene

Phenotypes From GWAS Catalog for SETDB1 Gene

Gene Ontology (GO) - Molecular Function for SETDB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003677 DNA binding IEA --
GO:0003682 chromatin binding IDA 27029610
GO:0005515 protein binding IPI,IEA 16682412
GO:0008168 methyltransferase activity IEA --
GO:0008270 zinc ion binding IEA --
genes like me logo Genes that share ontologies with SETDB1: view
genes like me logo Genes that share phenotypes with SETDB1: view

Animal Models for SETDB1 Gene

MGI Knock Outs for SETDB1:

Animal Model Products

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SETDB1 Gene

Localization for SETDB1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SETDB1 Gene

Nucleus. Cytoplasm. Chromosome. Note=Associated with non-pericentromeric regions of chromatin. Excluded from nucleoli and islands of condensed chromatin.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SETDB1 gene
Compartment Confidence
nucleus 5
cytosol 3
plasma membrane 2
cytoskeleton 2
extracellular 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SETDB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IMP,IDA 27732843
GO:0005654 nucleoplasm IDA,TAS --
GO:0005694 chromosome IEA --
GO:0005737 cytoplasm IMP 27732843
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with SETDB1: view

Pathways & Interactions for SETDB1 Gene

genes like me logo Genes that share pathways with SETDB1: view

Pathways by source for SETDB1 Gene

1 Cell Signaling Technology pathway for SETDB1 Gene
1 GeneTex pathway for SETDB1 Gene

Gene Ontology (GO) - Biological Process for SETDB1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006325 chromatin organization IEA --
GO:0007265 Ras protein signal transduction IMP 24623306
GO:0032259 methylation IEA --
GO:0033273 response to vitamin IEA --
GO:0034968 histone lysine methylation IEA --
genes like me logo Genes that share ontologies with SETDB1: view

No data available for SIGNOR curated interactions for SETDB1 Gene

Drugs & Compounds for SETDB1 Gene

(2) Drugs for SETDB1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
D-Lysine Approved, Experimental Nutra Full agonist, Agonist 0
s-adenosylhomocysteine Experimental Pharma 0

(1) Additional Compounds for SETDB1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
s-adenosylmethionine
  • (3S)-5'-[(3-amino-3-Carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
  • Acylcarnitine
  • AdoMet
  • S-(5'-Deoxyadenosin-5'-yl)-L-methionine
485-80-3
genes like me logo Genes that share compounds with SETDB1: view

Transcripts for SETDB1 Gene

mRNA/cDNA for SETDB1 Gene

5 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
17 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SETDB1 Gene

No ASD Table

Relevant External Links for SETDB1 Gene

GeneLoc Exon Structure for
SETDB1

Expression for SETDB1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SETDB1 Gene

Protein differential expression in normal tissues from HIPED for SETDB1 Gene

This gene is overexpressed in Testis (15.3), Peripheral blood mononuclear cells (11.2), Lung (8.1), Breast (8.1), and Plasma (6.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SETDB1 Gene



Protein tissue co-expression partners for SETDB1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SETDB1

SOURCE GeneReport for Unigene cluster for SETDB1 Gene:

Hs.643565

mRNA Expression by UniProt/SwissProt for SETDB1 Gene:

Q15047-SETB1_HUMAN
Tissue specificity: Widely expressed. High expression in testis.

Evidence on tissue expression from TISSUES for SETDB1 Gene

  • Bone marrow(4.2)
  • Liver(4.2)
  • Muscle(4.2)
  • Nervous system(3.9)
genes like me logo Genes that share expression patterns with SETDB1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SETDB1 Gene

Orthologs for SETDB1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SETDB1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SETDB1 31 30
  • 99.74 (n)
OneToOne
dog
(Canis familiaris)
Mammalia SETDB1 31 30
  • 92.29 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SETDB1 31 30
  • 91.98 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Setdb1 17 31 30
  • 88.98 (n)
rat
(Rattus norvegicus)
Mammalia Setdb1 30
  • 88.17 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SETDB1 31
  • 85 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia SETDB1 31
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves -- 31
  • 77 (a)
OneToMany
-- 31
  • 76 (a)
OneToMany
LOC101751150 30
  • 70.92 (n)
lizard
(Anolis carolinensis)
Reptilia SETDB1 31
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia setdb1 30
  • 70.84 (n)
Str.4156 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.16848 30
zebrafish
(Danio rerio)
Actinopterygii setdb1b 31 30
  • 62.55 (n)
OneToMany
setdb1a 31
  • 33 (a)
OneToMany
wufa04a12 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5926 30
fruit fly
(Drosophila melanogaster)
Insecta CG30426 32
  • 44 (a)
CG30422 32
  • 35 (a)
egg 31
  • 30 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea set-11 31
  • 26 (a)
ManyToMany
met-2 31
  • 20 (a)
ManyToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SET2 31
  • 10 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea Cin.12807 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.12807 30