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Browse SETDB1

Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus. Chromosome. Note=Associated with non-pericentromeric regions of chromatin. Excluded from nucleoli and islands of condensed chromatin.
Domain PF01429 Methyl-CpG binding domain
PF05033 Pre-SET motif
PF00856 SET domain
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. 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).

> Gene Ontology
 
Biological Process GO:0006342 chromatin silencing
GO:0006346 methylation-dependent chromatin silencing
GO:0006479 protein methylation
GO:0007265 Ras protein signal transduction
GO:0007584 response to nutrient
GO:0008213 protein alkylation
GO:0009991 response to extracellular stimulus
GO:0016458 gene silencing
GO:0016570 histone modification
GO:0016571 histone methylation
GO:0018022 peptidyl-lysine methylation
GO:0018205 peptidyl-lysine modification
GO:0031667 response to nutrient levels
GO:0031935 regulation of chromatin silencing
GO:0031937 positive regulation of chromatin silencing
GO:0032259 methylation
GO:0033273 response to vitamin
GO:0034968 histone lysine methylation
GO:0040029 regulation of gene expression, epigenetic
GO:0043414 macromolecule methylation
GO:0045471 response to ethanol
GO:0045814 negative regulation of gene expression, epigenetic
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0060968 regulation of gene silencing
GO:0090308 regulation of methylation-dependent chromatin silencing
GO:0090309 positive regulation of methylation-dependent chromatin silencing
GO:0097305 response to alcohol
GO:1902275 regulation of chromatin organization
GO:1905269 positive regulation of chromatin organization
Molecular Function GO:0003682 chromatin binding
GO:0008168 methyltransferase activity
GO:0008170 N-methyltransferase activity
GO:0008276 protein methyltransferase activity
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
GO:0016278 lysine N-methyltransferase activity
GO:0016279 protein-lysine N-methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
GO:0018024 histone-lysine N-methyltransferase activity
GO:0042054 histone methyltransferase activity
GO:1990841 promoter-specific chromatin binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04550 Signaling pathways regulating pluripotency of stem cells
hsa00310 Lysine degradation
Reactome R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-3214841: PKMTs methylate histone lysines
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SETDB1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SETDB1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 3.87; FDR: 0.023 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX STARS Score: 4.78; FDR: 0.006 Resistant to T cell-mediated killing
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SETDB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0880.733
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1080.946
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0660.96
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4110.257
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.4790.835
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3320.914
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1840.586
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0680.966
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3240.854
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4060.778
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1660.571
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2050.00612
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SETDB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277311.1011.10.0181
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.1011.10.0286
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SETDB1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SETDB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SETDB1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SETDB1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SETDB1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SETDB1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSETDB1
NameSET domain, bifurcated 1
Aliases KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SETDB1 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.