Browse BRD4

Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
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
 
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
 
KEGG -
Reactome -
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
  Literatures describing the relation between BRD4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29670088Metastatic Malignant NeoplasmInhibit immunityPVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix.
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
  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
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1510.648
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2450.905
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0810.958
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1480.557
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0070.998
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3470.917
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1840.596
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.1170.941
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2810.872
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.5230.656
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.2670.442
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0020.954
> Mutation difference between responders and non-responders
 
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 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) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916018.8-18.80.28
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59022.2-22.20.505
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
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
 
> Receptor
 
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of BRD4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between BRD4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolBRD4
Namebromodomain containing 4
Aliases HUNKI; HUNK1; chromosome-associated protein; bromodomain-containing 4; Protein HUNK1; Bromodomain-containing ......
Chromosomal Location19p13.12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting BRD4 collected from DrugBank database.
> Drugs from DrugBank database
 

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