SETDB1 [The Human Chemical-Genetic Interaction Map Project]

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======= SETDB1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SETDB1
  * **<color #00a2e8>Official Name</color>**: SET domain bifurcated histone lysine methyltransferase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9869|9869]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q15047|Q15047]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SETDB1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SETDB1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604396|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:15327775, ECO:0000269|PubMed:17952062, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|MBD|
|SET|
|Pre-SET|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|histone methyltransferase activity (H3-K9 specific)|
|positive regulation of methylation-dependent chromatin silencing|
|regulation of methylation-dependent chromatin silencing|
|positive regulation of chromatin silencing|
|negative regulation of single stranded viral RNA replication via double stranded DNA intermediate|
|histone H3-K9 methylation|
|regulation of single stranded viral RNA replication via double stranded DNA intermediate|
|histone H3-K9 modification|
|histone-lysine N-methyltransferase activity|
|regulation of chromatin silencing|
|promoter-specific chromatin binding|
|negative regulation of viral genome replication|
|histone lysine methylation|
|negative regulation of viral life cycle|
|response to vitamin|
|peptidyl-lysine methylation|
|histone methylation|
|regulation of viral genome replication|
|negative regulation of viral process|
|positive regulation of chromatin organization|
|chromosome|
|response to ethanol|
|regulation of gene silencing|
|protein alkylation|
|protein methylation|
|regulation of viral life cycle|
|positive regulation of chromosome organization|
|regulation of chromatin organization|
|regulation of viral process|
|response to nutrient|
|negative regulation of multi-organism process|
|regulation of symbiosis, encompassing mutualism through parasitism|
|response to alcohol|
|Ras protein signal transduction|
|macromolecule methylation|
|response to antibiotic|
|methylation|
|peptidyl-lysine modification|
|small GTPase mediated signal transduction|
|regulation of chromosome organization|
|histone modification|
|covalent chromatin modification|
|chromatin binding|
|response to nutrient levels|
|response to toxic substance|
|response to extracellular stimulus|
|positive regulation of organelle organization|
|intracellular membrane-bounded organelle|
|chromatin organization|
|regulation of multi-organism process|
|zinc ion binding|
|peptidyl-amino acid modification|
|response to drug|
|chromosome organization|
|positive regulation of cellular component organization|
|regulation of organelle organization|
|DNA binding|
|response to oxygen-containing compound|
|intracellular signal transduction|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp75|MK-1775 0.32μM R02 exp75]]|-1.77|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|1.74|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|1.77|
|[[:results:exp379|MSC2530818 10μM R07 exp379]]|2.04|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|2.16|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|2.41|
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|2.74|
|[[:results:exp59|UMK57 1μM R01 exp59]]|3.14|
|[[:results:exp312|2-Methoxyestradiol 0.55 to 1μM on day4 R07 exp312]]|3.48|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|5.91|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:a:atf7ip|ATF7IP]]|0.538|
|[[:human genes:i:id3|ID3]]|0.504|
|[[:human genes:c:cbx3|CBX3]]|0.495|
|[[:human genes:t:trim28|TRIM28]]|0.479|
|[[:human genes:a:atat1|ATAT1]]|0.471|
|[[:human genes:z:znf592|ZNF592]]|0.463|
|[[:human genes:b:brpf1|BRPF1]]|0.458|
|[[:human genes:e:ehmt2|EHMT2]]|0.458|
|[[:human genes:a:arl14ep|ARL14EP]]|0.439|
|[[:human genes:n:nsd1|NSD1]]|0.434|
|[[:human genes:m:mllt1|MLLT1]]|0.429|
|[[:human genes:a:aff1|AFF1]]|0.428|
|[[:human genes:d:ddx5|DDX5]]|0.418|
|[[:human genes:c:ccdc101|CCDC101]]|0.408|
|[[:human genes:t:taf5l|TAF5L]]|0.406|
|[[:human genes:a:ambra1|AMBRA1]]|0.404|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 69/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|2/28|
|blood|9/28|
|bone|7/25|
|breast|1/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|3/17|
|esophagus|4/13|
|fibroblast|0/1|
|gastric|1/15|
|kidney|1/21|
|liver|2/20|
|lung|5/75|
|lymphocyte|0/14|
|ovary|2/26|
|pancreas|2/24|
|peripheral nervous system|2/16|
|plasma cell|3/15|
|prostate|1/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|4/22|
|urinary tract|3/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1249
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.48 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SETDB1 Expression in NALM6 Cells: 6.48'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>