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BRD4 bromodomain containing 4 [ Homo sapiens (human) ]

Gene ID: 23476, updated on 25-Nov-2021

Summary

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Official Symbol
BRD4provided by HGNC
Official Full Name
bromodomain containing 4provided by HGNC
Primary source
HGNC:HGNC:13575
See related
Ensembl:ENSG00000141867 MIM:608749
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CAP; MCAP; HUNK1; HUNKI
Summary
The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in placenta (RPKM 10.8), testis (RPKM 9.2) and 25 other tissues See more
Orthologs
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Genomic context

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See BRD4 in Genome Data Viewer
Location:
19p13.12
Exon count:
23
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 19 NC_000019.10 (15235519..15332539, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (15346330..15443350, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene notch receptor 3 Neighboring gene microRNA 6795 Neighboring gene epoxide hydrolase 3 Neighboring gene A-kinase anchoring protein 8 Neighboring gene Sharpr-MPRA regulatory region 9920 Neighboring gene A-kinase anchoring protein 8 like

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Inhibition of BRD4 Suppresses the Growth of Esophageal Squamous Cell Carcinoma. Niu H, et al. Cancer Invest, 2021 Nov. PMID 34519605
  2. Stromal induction of BRD4 phosphorylation Results in Chromatin Remodeling and BET inhibitor Resistance in Colorectal Cancer. Wang W, et al. Nat Commun, 2021 Jul 21. PMID 34290255, Free PMC Article
  3. Bromodomain-containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics. Li L, et al. Cancer Sci, 2021 Oct. PMID 34252226, Free PMC Article
  4. Bromodomain-containing Protein 4 Is a Favourable Prognostic Factor in Breast Cancer Patients. Suzuki C, et al. Anticancer Res, 2021 Jul. PMID 34230156
  5. Targeting BRD4 in acute myeloid leukemia with partial tandem duplication of the MLL gene. Bill M, et al. Haematologica, 2021 Sep 1. PMID 33979989, Free PMC Article

See all (382) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Targeting BRD4 in acute myeloid leukemia with partial tandem duplication of the MLL gene.
    Title: Targeting BRD4 in acute myeloid leukemia with partial tandem duplication of the <i>MLL</i> gene.
  2. Inhibition of BRD4 Suppresses the Growth of Esophageal Squamous Cell Carcinoma.
    Title: Inhibition of BRD4 Suppresses the Growth of Esophageal Squamous Cell Carcinoma.
  3. A BRD4-mediated elongation control point primes transcribing RNA polymerase II for 3'-processing and termination.
    Title: A BRD4-mediated elongation control point primes transcribing RNA polymerase II for 3'-processing and termination.
  4. BRD4 inhibition sensitizes cervical cancer to radiotherapy by attenuating DNA repair.
    Title: BRD4 inhibition sensitizes cervical cancer to radiotherapy by attenuating DNA repair.
  5. LncRNA XIST silencing protects against sepsis-induced acute liver injury via inhibition of BRD4 expression.
    Title: LncRNA XIST silencing protects against sepsis-induced acute liver injury via inhibition of BRD4 expression.
  6. Bromodomain-containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics.
    Title: Bromodomain-containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics.
  7. Bromodomain Epigenetic Protein Promotes Metastatic Potential in Melanoma Cells through Increased Invasiveness and Decreased Macrophage-Mediated Phagocytosis.
    Title: Bromodomain Epigenetic Protein Promotes Metastatic Potential in Melanoma Cells through Increased Invasiveness and Decreased Macrophage-Mediated Phagocytosis.
  8. circCELSR1 facilitates ovarian cancer proliferation and metastasis by sponging miR-598 to activate BRD4 signals.
    Title: circCELSR1 facilitates ovarian cancer proliferation and metastasis by sponging miR-598 to activate BRD4 signals.
  9. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.
    Title: Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation.
  10. Discovery of RSV-Induced BRD4 Protein Interactions Using Native Immunoprecipitation and Parallel Accumulation-Serial Fragmentation (PASEF) Mass Spectrometry.
    Title: Discovery of RSV-Induced BRD4 Protein Interactions Using Native Immunoprecipitation and Parallel Accumulation-Serial Fragmentation (PASEF) Mass Spectrometry.
Submit: New GeneRIF Correction See all GeneRIFs (283)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
De Lange syndrome
MedGen: C0270972 GeneReviews: Cornelia de Lange Syndrome
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
HIV-1 replication is inhibited by BRD4; siRNA-mediated knockdown allows for Tat-induced latency reversal PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat The RxL or KxL motif and the polybasic cluster of HIV-1 Tat and BRD4 exhibit similar importance for P-TEFb activation PubMed
tat The C-terminal 34 residues (1329-1362) of BRD4 are crucial for interaction with P-TEFb. Overexpression of the BRD4 P-TEFb-interacting domain disrupts the interaction between HIV-1 Tat and P-TEFb PubMed
tat CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEXIM1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1) PubMed
tat Phosphorylation of CDK9 at position Ser175 regulates the competition between HIV-1 Tat and BRD4 for P-TEFb binding PubMed
tat Brd4 inhibits HIV-1 Tat-human super elongation complex (components AFF4, ELL2, CycT1, and CDK9) by competing with HIV-1 Tat for binding to P-TEFb on HIV-1 promoter PubMed
tat JQ1, a small molecule inhibitor of Brd4, directly dissociates Brd4 from HIV-1 promoter and promotes subsequently HIV-1 Tat binding to HIV-1 promoter, resulting in increased phosphorylation of RNA polymerase II and viral transcription PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables P-TEFb complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables RNA polymerase II C-terminal domain binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables RNA polymerase II CTD heptapeptide repeat kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables chromatin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables lysine-acetylated histone binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables lysine-acetylated histone binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleosomal histone binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables p53 binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables transcription coactivator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables transcription coregulator activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
  
involved_in chromatin remodeling IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
acts_upstream_of_or_within positive regulation of G2/M transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of histone H3-K36 trimethylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of transcription elongation from RNA polymerase II promoter IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in positive regulation of transcription elongation from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within positive regulation of transcription elongation from RNA polymerase II promoter IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of phosphorylation of RNA polymerase II C-terminal domain IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within regulation of transcription involved in G1/S transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of transcription, DNA-templated IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Component Evidence Code Pubs
is_active_in chromatin IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in condensed nuclear chromosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
bromodomain-containing protein 4
Names
chromosome-associated protein
mitotic chromosome-associated protein
NP_001317313.1
NP_001366220.1
NP_001366221.1
NP_055114.1
NP_490597.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001330384.2 → NP_001317313.1  bromodomain-containing protein 4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (short) differs in the 3' UTR and coding region compared to variant long. The resulting isoform (short) is shorter and has a distinct C-terminus compared to isoform long.
    Source sequence(s)
    AC004798, AC005776, BC035266
    Consensus CDS
    CCDS82307.1
    UniProtKB/Swiss-Prot
    O60885
    UniProtKB/TrEMBL
    A0A024R7H8
    Related
    ENSP00000353112.4, ENST00000360016.9
    Conserved Domains (3) summary
    cd05497
    Location:58 → 164
    Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    cd05498
    Location:353 → 454
    Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    pfam17035
    Location:609 → 673
    BET; Bromodomain extra-terminal - transcription regulation

  2. NM_001379291.1 → NP_001366220.1  bromodomain-containing protein 4 isoform long

    Status: REVIEWED

    Source sequence(s)
    AC004257, AC004798, AC005776
    Related
    ENSP00000506350.1, ENST00000679869.1
    Conserved Domains (5) summary
    cd05497
    Location:58 → 164
    Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    cd05498
    Location:353 → 454
    Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    PRK03427
    Location:809 → 922
    PRK03427; cell division protein ZipA; Provisional
    pfam17035
    Location:609 → 673
    BET; Bromodomain extra-terminal - transcription regulation
    pfam17105
    Location:1319 → 1362
    BRD4_CDT; C-terminal domain of bromodomain protein 4

  3. NM_001379292.1 → NP_001366221.1  bromodomain-containing protein 4 isoform short

    Status: REVIEWED

    Source sequence(s)
    AC004798, AC005776
    Conserved Domains (3) summary
    cd05497
    Location:58 → 164
    Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    cd05498
    Location:353 → 454
    Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    pfam17035
    Location:609 → 673
    BET; Bromodomain extra-terminal - transcription regulation

  4. NM_014299.3 → NP_055114.1  bromodomain-containing protein 4 isoform short

    See identical proteins and their annotated locations for NP_055114.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (short) differs in the 3' UTR and coding region compared to variant long. The resulting isoform (short) is shorter and has a distinct C-terminus compared to isoform long.
    Source sequence(s)
    AC004798, BC035266, Y12059
    Consensus CDS
    CCDS46004.1
    UniProtKB/Swiss-Prot
    O60885
    Related
    ENSP00000360901.3, ENST00000371835.8
    Conserved Domains (3) summary
    cd05497
    Location:58 → 164
    Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    cd05498
    Location:353 → 454
    Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    pfam17035
    Location:609 → 673
    BET; Bromodomain extra-terminal - transcription regulation

  5. NM_058243.3 → NP_490597.1  bromodomain-containing protein 4 isoform long

    See identical proteins and their annotated locations for NP_490597.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (long) encodes the full length isoform.
    Source sequence(s)
    AC004257, AC004798, AF386649, BC035266
    Consensus CDS
    CCDS12328.1
    UniProtKB/Swiss-Prot
    O60885
    Related
    ENSP00000263377.1, ENST00000263377.6
    Conserved Domains (5) summary
    cd05497
    Location:58 → 164
    Bromo_Brdt_I_like; Bromodomain, Brdt_like subfamily, repeat I. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    cd05498
    Location:353 → 454
    Bromo_Brdt_II_like; Bromodomain, Brdt_like subfamily, repeat II. Human Brdt is a testis-specific member of the BET subfamily of bromodomain proteins; the first bromodomain in Brdt has been shown to be essential for male germ cell differentiation. Bromodomains are 110 amino ...
    PRK03427
    Location:809 → 922
    PRK03427; cell division protein ZipA; Provisional
    pfam17035
    Location:609 → 673
    BET; Bromodomain extra-terminal - transcription regulation
    pfam17105
    Location:1319 → 1362
    BRD4_CDT; C-terminal domain of bromodomain protein 4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p13 Primary Assembly

    Range
    15235519..15332539 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60885.2 GenPept UniProtKB/Swiss-Prot:O60885

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