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Aliases for BRD4 Gene

Aliases for BRD4 Gene

  • Bromodomain Containing 4 2 3 5
  • Chromosome-Associated Protein 2 3
  • Bromodomain-Containing 4 2 3
  • HUNK1 3 4
  • Protein HUNK1 4
  • HUNKI 3
  • MCAP 3
  • CAP 3

External Ids for BRD4 Gene

Previous GeneCards Identifiers for BRD4 Gene

  • GC19M015727
  • GC19M015193
  • GC19M015209
  • GC19M015348
  • GC19M014916

Summaries for BRD4 Gene

Entrez Gene Summary for BRD4 Gene

  • 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]

GeneCards Summary for BRD4 Gene

BRD4 (Bromodomain Containing 4) is a Protein Coding gene. Diseases associated with BRD4 include nut midline carcinoma and extragonadal seminoma. Among its related pathways are EphB-EphrinB Signaling and Beta-Adrenergic Signaling. GO annotations related to this gene include chromatin binding and lysine-acetylated histone binding. An important paralog of this gene is BRD3.

UniProtKB/Swiss-Prot for BRD4 Gene

  • 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.

  • 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.

Tocris Summary for BRD4 Gene

  • Bromodomains (BRDs) are epigenetic reader domains that selectively recognize acetylated lysine residues on the tails of histone proteins, and are the only known protein modules that can target acetylated lysine residues.

Gene Wiki entry for BRD4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for BRD4 Gene

Genomics for BRD4 Gene

Regulatory Elements for BRD4 Gene

Promoters for BRD4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around BRD4 on UCSC Golden Path with GeneCards custom track

Genomic Location for BRD4 Gene

Chromosome:
19
Start:
15,235,519 bp from pter
End:
15,332,545 bp from pter
Size:
97,027 bases
Orientation:
Minus strand

Genomic View for BRD4 Gene

Genes around BRD4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BRD4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BRD4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BRD4 Gene

Proteins for BRD4 Gene

  • Protein details for BRD4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60885-BRD4_HUMAN
    Recommended name:
    Bromodomain-containing protein 4
    Protein Accession:
    O60885
    Secondary Accessions:
    • O60433
    • Q4G0X8
    • Q86YS8
    • Q96PD3

    Protein attributes for BRD4 Gene

    Size:
    1362 amino acids
    Molecular mass:
    152219 Da
    Quaternary structure:
    • Interacts with p53/TP53; the interaction is direct. Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex. Interacts with RELA (when acetylated at Lys-310). Interacts (via NET domain) with WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5. Isoform B: interacts with NCAPD3 and SMC2. Interacts with bovine papillomavirus type 1 regulatory protein E2 and human herpes virus-8 (HHV-8) protein LANA. These interactions may serve for the tethering of viral genomes to host mitotic chromosomes allowing successful partitioning of the viral genome during cell division. Interacts with Epstein-Barr virus (EBV) protein EBNA1; this interaction facilitates transcriptional activation by EBNA1.
    Miscellaneous:
    • Some specific inhibitors of BRD4 that prevent binding to acetylated histones by binding Asn-140 and Asn-433 are promising therapeutic molecules for the treatment of leukemias. JQ1, a thieno-triazolo-1,4-diazepine derivative, and I-BET, a benzodiazepine derivative, have been tested on tumors with success (PubMed:20871596, PubMed:21068722, PubMed:21964340). Treatment with GSK1210151A (I-BET151, a I-BET derivative) has strong effets on mixed lineage leukemia and promotes myeloid differentiation and leukemia stem-cell depletion (PubMed:21964340).
    SequenceCaution:
    • Sequence=AAC27978.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for BRD4 Gene

    Alternative splice isoforms for BRD4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for BRD4 Gene

Proteomics data for BRD4 Gene at MOPED

Post-translational modifications for BRD4 Gene

  • Phosphorylation by CK2 disrupt the intramolecular binding between the bromo domain 2 and the NPS region and promotes binding between the NPS and the BID regions, leading to activate the protein and promote binding to acetylated histones. In absence of phosphorylation, BRD4 does not localize to p53/TP53 target gene promoters, phosphorylation promoting recruitment to p53/TP53 target promoters.
  • Ubiquitination at Lys 99
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for BRD4 (BRD4)

No data available for DME Specific Peptides for BRD4 Gene

Domains & Families for BRD4 Gene

Gene Families for BRD4 Gene

Protein Domains for BRD4 Gene

Suggested Antigen Peptide Sequences for BRD4 Gene

Graphical View of Domain Structure for InterPro Entry

O60885

UniProtKB/Swiss-Prot:

BRD4_HUMAN :
  • The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5).
Domain:
  • The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5).
  • The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex (PubMed:16109376, PubMed:16109377). It is also required for maintenance of higher-order chromatin structure (PubMed:22334664).
  • The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-433, respectively (PubMed:20871596). The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3 (PubMed:22464331). A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-433, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives (PubMed:22137933, PubMed:22136404, PubMed:23517011, PubMed:23530754).
  • Contains 2 bromo domains.
  • Contains 1 NET domain.
genes like me logo Genes that share domains with BRD4: view

Function for BRD4 Gene

Molecular function for BRD4 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot 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.
genes like me logo Genes that share phenotypes with BRD4: view

Animal Model Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for BRD4 Gene

Localization for BRD4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for BRD4 Gene

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.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for BRD4 Gene COMPARTMENTS Subcellular localization image for BRD4 gene
Compartment Confidence
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for BRD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA --
genes like me logo Genes that share ontologies with BRD4: view

Pathways & Interactions for BRD4 Gene

genes like me logo Genes that share pathways with BRD4: view

Pathways by source for BRD4 Gene

1 GeneTex pathway for BRD4 Gene

SIGNOR curated interactions for BRD4 Gene

Activates:

Gene Ontology (GO) - Biological Process for BRD4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000083 regulation of transcription involved in G1/S transition of mitotic cell cycle IMP 18039861
GO:0006338 chromatin remodeling IDA 23728299
GO:0006974 cellular response to DNA damage stimulus IMP 23728299
GO:0016568 chromatin modification IEA --
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IDA 23086925
genes like me logo Genes that share ontologies with BRD4: view

Drugs & Compounds for BRD4 Gene

(33) Drugs for BRD4 Gene - From: ApexBio, DGIdb, Tocris, and ClinicalTrials

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
CPI-203 Pharma BET bromodomain inhibitor 0
I-BET-762 Pharma BET inhibitor,highly potent 0
MS436 Pharma BRD4 inhibitor 0
(+)-JQ1 Pharma Potent, selective BET bromodomain inhibitor; cell permeable 0
Pharmaceutical Solutions Pharma 7004

(4) Additional Compounds for BRD4 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
I-BET 151 dihydrochloride
Ischemin sodium salt
LY 303511
154447-38-8
PFI 1
1403764-72-6

(5) Tocris Compounds for BRD4 Gene

Compound Action Cas Number
(+)-JQ1 Potent, selective BET bromodomain inhibitor; cell permeable 1268524-70-4
I-BET 151 dihydrochloride BET bromodomain inhibitor; also promotes differentiation of hiPSCs into megakaryocytes
Ischemin sodium salt CBP inhibitor; cell permeable
LY 303511 Negative control of LY 294002 (Cat. No. 1130) 154447-38-8
PFI 1 BET bromodomain inhibitor 1403764-72-6

(12) ApexBio Compounds for BRD4 Gene

Compound Action Cas Number
(-)-JQ1 BET bromodomain inhibitor 1268524-71-5
Bromodomain Inhibitor, (+)-JQ1 BET bromodomain inhibitor 1268524-70-4
CPI-203 BET bromodomain inhibitor 1446144-04-2
I-BET151 (GSK1210151A) Selective BET inhibitor 1300031-49-5
I-BET-762 BET inhibitor,highly potent 1260907-17-2
MS436 BRD4 inhibitor 1395084-25-9
OF-1 BRPF1B and BRPF2 bromodomain inhibitor 919973-83-4
OTX-015 BRD inhibitor 202590-98-5
PFI-1 (PF-6405761) BET inhibitor 1403764-72-6
RVX-208 Potent BET bromodomain inhibitor 1044870-39-4
UNC1215 Chemical probe for the methyllysine (Kme) 1415800-43-9
UNC669 L3MBTL antagonist,potent and selective 1314241-44-5
genes like me logo Genes that share compounds with BRD4: view

Transcripts for BRD4 Gene

Unigene Clusters for BRD4 Gene

Bromodomain containing 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for BRD4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17a · 17b ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24a ·
SP1: -
SP2:
SP3:
SP4:
SP5: -
SP6: - -
SP7: - -
SP8: -
SP9:
SP10: -
SP11:
SP12:
SP13:

ExUns: 24b ^ 25 ^ 26 ^ 27 ^ 28 ^ 29 ^ 30
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:

Relevant External Links for BRD4 Gene

GeneLoc Exon Structure for
BRD4
ECgene alternative splicing isoforms for
BRD4

Expression for BRD4 Gene

mRNA expression in normal human tissues for BRD4 Gene

Protein differential expression in normal tissues from HIPED for BRD4 Gene

This gene is overexpressed in Adrenal (13.6), Peripheral blood mononuclear cells (10.0), and Lymph node (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for BRD4 Gene



SOURCE GeneReport for Unigene cluster for BRD4 Gene Hs.187763

mRNA Expression by UniProt/SwissProt for BRD4 Gene

O60885-BRD4_HUMAN
Tissue specificity: Ubiquitously expressed.
genes like me logo Genes that share expression patterns with BRD4: view

Protein tissue co-expression partners for BRD4 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for BRD4 Gene

Orthologs for BRD4 Gene

This gene was present in the common ancestor of animals.

Orthologs for BRD4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia BRD4 35
  • 96.88 (n)
  • 96.48 (a)
BRD4 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia BRD4 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia BRD4 36
  • 97 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia BRD4 36
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Brd4 36
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia BRD4 36
  • 88 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOC100859056 35
  • 77.15 (n)
  • 81.11 (a)
BRD4 36
  • 79 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia BRD4 36
  • 81 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii brd4 36
  • 55 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta fs(1)h 37
  • 53 (a)
fs(1)h 36
  • 24 (a)
OneToMany
Species with no ortholog for BRD4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for BRD4 Gene

ENSEMBL:
Gene Tree for BRD4 (if available)
TreeFam:
Gene Tree for BRD4 (if available)

Paralogs for BRD4 Gene

Paralogs for BRD4 Gene

genes like me logo Genes that share paralogs with BRD4: view

Variants for BRD4 Gene

Sequence variations from dbSNP and Humsavar for BRD4 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs35177876 - 15,272,991(+) GGCTG(A/G)CTGGG reference, missense
rs55805532 - 15,264,504(+) CGTAG(C/G)CGGCG reference, missense
rs55970906 - 15,256,127(+) CTTTG(C/T)TTTTT reference, missense
rs34362023 - 15,255,552(+) ATACG(A/T)GGGAG reference, missense
rs35824241 - 15,255,338(+) CATAG(C/T)GCTCC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for BRD4 Gene

Variant ID Type Subtype PubMed ID
esv34154 CNV Loss 18971310
nsv911132 CNV Loss 21882294
esv271038 CNV Insertion 20981092

Variation tolerance for BRD4 Gene

Residual Variation Intolerance Score: 1.79% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.96; 49.43% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for BRD4 Gene

HapMap Linkage Disequilibrium report
BRD4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BRD4 Gene

Disorders for BRD4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for BRD4 Gene - From: Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
nut midline carcinoma
  • nuclear protein in testis midline carcinoma
extragonadal seminoma
  • primary extragonadal seminoma
- elite association - COSMIC cancer census association via MalaCards
Search BRD4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

BRD4_HUMAN
  • Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. {ECO:0000269 PubMed:11733348, ECO:0000269 PubMed:12543779}.

Relevant External Links for BRD4

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
BRD4
genes like me logo Genes that share disorders with BRD4: view

No data available for Genatlas for BRD4 Gene

Publications for BRD4 Gene

  1. A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. (PMID: 10938129) Dey A. … Ozato K. (Mol. Cell. Biol. 2000) 2 3 23 67
  2. Abrogation of the Brd4-positive transcription elongation factor B complex by papillomavirus E2 protein contributes to viral oncogene repression. (PMID: 19846528) Yan J. … You J. (J. Virol. 2010) 3 23
  3. Chromatin adaptor Brd4 modulates E2 transcription activity and protein stability. (PMID: 19038968) Lee A.Y. … Chiang C.M. (J. Biol. Chem. 2009) 3 23
  4. Proteasomal degradation of the papillomavirus E2 protein is inhibited by overexpression of bromodomain-containing protein 4. (PMID: 19211738) Gagnon D. … Archambault J. (J. Virol. 2009) 3 23
  5. Identification of the P-TEFb complex-interacting domain of Brd4 as an inhibitor of HIV-1 replication by functional cDNA library screening in MT-4 cells. (PMID: 18996376) Urano E. … Komano J. (FEBS Lett. 2008) 3 23

Products for BRD4 Gene

Sources for BRD4 Gene

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