TISIDB

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
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=Associates with acetylated chromatin. Released from chromatin upon deacetylation of histones that can be triggered by different signals such as activation of the JNK pathway or nocodazole treatment.
Domain	PF17035 Bromodomain extra-terminal - transcription regulation PF17105 C-terminal domain of bromodomain protein 4 PF00439 Bromodomain
Function	Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters: BRD4 is required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II. Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II. According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo (PubMed:22509028). In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters. ; FUNCTION: Isoform B: Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AFX/H2A.x phosphorylation.

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle GO:0000086 G2/M transition of mitotic cell cycle GO:0006354 DNA-templated transcription, elongation GO:0006368 transcription elongation from RNA polymerase II promoter GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0007346 regulation of mitotic cell cycle GO:0010389 regulation of G2/M transition of mitotic cell cycle GO:0010971 positive regulation of G2/M transition of mitotic cell cycle GO:0032784 regulation of DNA-templated transcription, elongation GO:0032786 positive regulation of DNA-templated transcription, elongation GO:0032968 positive regulation of transcription elongation from RNA polymerase II promoter GO:0034243 regulation of transcription elongation from RNA polymerase II promoter GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044839 cell cycle G2/M phase transition GO:0044843 cell cycle G1/S phase transition GO:0045787 positive regulation of cell cycle GO:0045931 positive regulation of mitotic cell cycle GO:0050727 regulation of inflammatory response GO:0070816 phosphorylation of RNA polymerase II C-terminal domain GO:0090068 positive regulation of cell cycle process GO:1901407 regulation of phosphorylation of RNA polymerase II C-terminal domain GO:1901987 regulation of cell cycle phase transition GO:1901989 positive regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1901992 positive regulation of mitotic cell cycle phase transition GO:1902749 regulation of cell cycle G2/M phase transition GO:1902751 positive regulation of cell cycle G2/M phase transition
Molecular Function	GO:0000993 RNA polymerase II core binding GO:0001098 basal transcription machinery binding GO:0001099 basal RNA polymerase II transcription machinery binding GO:0002039 p53 binding GO:0003682 chromatin binding GO:0042393 histone binding GO:0043175 RNA polymerase core enzyme binding GO:0070063 RNA polymerase binding GO:0070577 lysine-acetylated histone binding
Cellular Component	GO:0000793 condensed chromosome GO:0000794 condensed nuclear chromosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between BRD4 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

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Literatures describing the relation between BRD4 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29670088	Metastatic Malignant Neoplasm	Inhibit immunity	PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix.

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
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

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Statistical results of BRD4 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	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
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	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
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

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Points in the above scatter plot represent the expression difference of BRD4 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	0.151	0.648
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.245	0.905
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.081	0.958
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.148	0.557
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.007	0.998
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.347	0.917
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.184	0.596
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.117	0.941
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.281	0.872
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.523	0.656
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	1.267	0.442
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.002	0.954

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of BRD4 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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	18.8	-18.8	0.28
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	0	0	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	0	0	1

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of BRD4. 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	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of BRD4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by BRD4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of BRD4. 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	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of BRD4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between BRD4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	BRD4
Name	bromodomain containing 4
Aliases	HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location	19p13.12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting BRD4 collected from DrugBank database.

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

Browse BRD4