TISIDB

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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 [ TOP ]
There is no record.

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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

[ TOP ]

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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 3.87; FDR: 0.023	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.78; FDR: 0.006	Resistant to T cell-mediated killing
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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

[ TOP ]

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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.088	0.733
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.108	0.946
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.066	0.96
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.411	0.257
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.479	0.835
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.332	0.914
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.184	0.586
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.068	0.966
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.324	0.854
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.406	0.778
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.166	0.571
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.205	0.00612

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	11.1	0	11.1	0.0181
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	11.1	0	11.1	0.0286
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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 [ TOP ]

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SETDB1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SETDB1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SETDB1
Name	SET domain, bifurcated 1
Aliases	KG1T; KIAA0067; ESET; KMT1E; TDRD21; tudor domain containing 21; H3-K9-HMTase4; ERG-associated protein with ......
Chromosomal Location	1q21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SETDB1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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