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BRD4 (bromodomain containing 4)

Written2007-02Anna Collin
Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

(Note : for Links provided by Atlas : click)

Identity

Alias_namesbromodomain-containing 4
Alias_symbol (synonym)HUNKI
MCAP
CAP
HUNK1
Other alias
HGNC (Hugo) BRD4
LocusID (NCBI) 23476
Atlas_Id 837
Location 19p13.12  [Link to chromosome band 19p13]
Location_base_pair Starts at 15252995 and ends at 15332543 bp from pter ( according to hg19-Feb_2009)  [Mapping BRD4.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BRD4 (19p13.12) / BRD4 (19p13.12)BRD4 (19p13.12) / NUTM1 (15q14)CD99L2 (Xq28) / BRD4 (19p13.12)
EPS15L1 (19p13.11) / BRD4 (19p13.12)NUTM1 (15q14) / BRD4 (19p13.12)RARA (17q21.2) / BRD4 (19p13.12)

DNA/RNA

Description The gene consists of 20 exons that span approximately 43 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon and stop codon are located to exon 2 and exon 20, respectively.
Transcription Two isoforms of BRD4 have been reported. The "BRD4 long isoform" corresponds to the ordinary full length transcript while the "BRD4 short isoform" corresponds to an alternative splicing variant lacking exons 12-20. The "BRD4 long variant" encodes a 6.0 kb transcript and the "BRD4 short variant" encodes a 4.4 kb transcript.

Protein

Description BRD4 belongs to the BET subgroup of the bromodomain superfamily and contains 2 bromodomains and a conserved ET-domain.
The open reading frame encodes a 1362 amino acid protein with a molecular weight of 200 kDa.
Expression Northen blot analysis has shown an ubiquitous normal expression of both BRD4 isoforms.
Localisation Nuclear.
Function A striking feature of BRD4 is its association with euchromatic regions of mitotic chromosomes. By this association, the protein exerts its function as regulator of cell cycle progression from G2 to M but also in the G1 to S transition. It has also been suggested that the association of BRD4 to chromatin is important for the transmission of a transcriptional memory during cell division.

Implicated in

Note
  
Entity Carcinoma with t(15;19)(q14;p13) translocation.
Prognosis Carcinoma with t(15;19) translocation is invariably fatal with a rapid clinical course when located to the midline thoracic, head and neck structures. One tumor, displaying the cytogenetic and molecular cytogenetic features of carcinoma with t(15;19) translocation, but located to the iliac bone, has been reported as successfully cured.
Cytogenetics t(15;19)(q14;p13) [reported breakpoints: t(15;19)(q11-15;p13)].
Hybrid/Mutated Gene The t(15;19)(q14;p13) results in a BRD4-NUT chimeric gene where exon 10 of BRD4 is fused to exon 2 of NUT.
Abnormal Protein The BRD4-NUT fusion protein is composed of the N-terminal of BRD4 (amino acids 1-720 out of 1372) and almost the entire protein sequence of NUT (amino acids 6-1127). The N-terminal of BRD4 includes bromodomains 1 and 2 and other, less well characterized functional domains.
Oncogenesis It has been suggested that the oncogenic effect of the NUT-BRD4 fusion is caused not only by the abnormal regulation of NUT by BRD4 promoter elements but also by the consequent ectopic expression of NUT in non-germinal tissues.
  

Breakpoints

Note The vast majority of reported 19p breakpoints were assigned to band 19p13, the exception being the cytogenetic interpretation of a 19q13 breakpoint reported once. The reported breakpoints on chromosome 15 have varied (15q11-q15).

Bibliography

The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis.
Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K
Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (15) : 8758-8763.
PMID 12840145
 
A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition.
Dey A, Ellenberg J, Farina A, Coleman AE, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K
Molecular and cellular biology. 2000 ; 20 (17) : 6537-6549.
PMID 10938129
 
Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy.
Engleson J, Soller M, Panagopoulos I, Dahlén A, Dictor M, Jerkeman M
BMC cancer. 2006 ; 6 : page 69.
PMID 16542442
 
You bet-cha: a novel family of transcriptional regulators.
Florence B, Faller DV
Frontiers in bioscience : a journal and virtual library. 2001 ; 6 : D1008-D1018.
PMID 11487468
 
Midline carcinoma of children and young adults with NUT rearrangement.
French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 ; 22 (20) : 4135-4139.
PMID 15483023
 
BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.
French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA
Cancer research. 2003 ; 63 (2) : 304-307.
PMID 12543779
 
Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19).
Kees UR, Mulcahy MT, Willoughby ML
The American journal of pediatric hematology/oncology. 1991 ; 13 (4) : 459-464.
PMID 1785673
 
A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase.
Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K
Molecular and cellular biology. 2002 ; 22 (18) : 6509-6520.
PMID 12192049
 
Carcinoma with t(15;19) translocation.
Marx A, French CA, Fletcher JA
In..
 
Successful treatment of a child with t(15;19)-positive tumor.
Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA
Pediatric blood & cancer. 2007 ; 49 (7) : 1015-1017.
PMID 16435379
 
Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes.
You J, Croyle JL, Nishimura A, Ozato K, Howley PM
Cell. 2004 ; 117 (3) : 349-360.
PMID 15109495
 

Citation

This paper should be referenced as such :
Collin, A
BRD4 (bromodomain containing 4)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):180-181.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/BRD4ID837ch19p13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(14;19)(q32;p13) IGH/EPOR::t(14;19)(q32;p13) IGH/BRD4 ?


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Midline Carcinoma: t(15;19)(q14;p13) BRD4/NUTM1


External links

Nomenclature
HGNC (Hugo)BRD4   13575
Cards
AtlasBRD4ID837ch19p13
Entrez_Gene (NCBI)BRD4  23476  bromodomain containing 4
AliasesCAP; HUNK1; HUNKI; MCAP
GeneCards (Weizmann)BRD4
Ensembl hg19 (Hinxton)ENSG00000141867 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000141867 [Gene_View]  chr19:15252995-15332543 [Contig_View]  BRD4 [Vega]
ICGC DataPortalENSG00000141867
TCGA cBioPortalBRD4
AceView (NCBI)BRD4
Genatlas (Paris)BRD4
WikiGenes23476
SOURCE (Princeton)BRD4
Genetics Home Reference (NIH)BRD4
Genomic and cartography
GoldenPath hg38 (UCSC)BRD4  -     chr19:15252995-15332543 -  19p13.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BRD4  -     19p13.12   [Description]    (hg19-Feb_2009)
EnsemblBRD4 - 19p13.12 [CytoView hg19]  BRD4 - 19p13.12 [CytoView hg38]
Mapping of homologs : NCBIBRD4 [Mapview hg19]  BRD4 [Mapview hg38]
OMIM608749   
Gene and transcription
Genbank (Entrez)AF252390 AF386649 AK307664 BC000156 BC008354
RefSeq transcript (Entrez)NM_001330384 NM_014299 NM_058243
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)BRD4
Cluster EST : UnigeneHs.187763 [ NCBI ]
CGAP (NCI)Hs.187763
Alternative Splicing GalleryENSG00000141867
Gene ExpressionBRD4 [ NCBI-GEO ]   BRD4 [ EBI - ARRAY_EXPRESS ]   BRD4 [ SEEK ]   BRD4 [ MEM ]
Gene Expression Viewer (FireBrowse)BRD4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23476
GTEX Portal (Tissue expression)BRD4
Human Protein AtlasENSG00000141867-BRD4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO60885   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO60885  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO60885
Splice isoforms : SwissVarO60885
PhosPhoSitePlusO60885
Domaine pattern : Prosite (Expaxy)BROMODOMAIN_1 (PS00633)    BROMODOMAIN_2 (PS50014)    NET (PS51525)   
Domains : Interpro (EBI)BRD4_CDT    Bromodomain    Bromodomain_CS    NET_dom   
Domain families : Pfam (Sanger)BET (PF17035)    BRD4_CDT (PF17105)    Bromodomain (PF00439)   
Domain families : Pfam (NCBI)pfam17035    pfam17105    pfam00439   
Domain families : Smart (EMBL)BROMO (SM00297)  
Conserved Domain (NCBI)BRD4
DMDM Disease mutations23476
Blocks (Seattle)BRD4
PDB (SRS)###############################################################################################################################################################################################################################################################   
PDB (PDBSum)###############################################################################################################################################################################################################################################################   
PDB (IMB)###############################################################################################################################################################################################################################################################   
PDB (RSDB)###############################################################################################################################################################################################################################################################   
Structural Biology KnowledgeBase###############################################################################################################################################################################################################################################################   
SCOP (Structural Classification of Proteins)###############################################################################################################################################################################################################################################################   
CATH (Classification of proteins structures)###############################################################################################################################################################################################################################################################   
SuperfamilyO60885
Human Protein Atlas [tissue]ENSG00000141867-BRD4 [tissue]
Peptide AtlasO60885
HPRD10574
IPIIPI00440727   IPI00440728   IPI00477699   
Protein Interaction databases
DIP (DOE-UCLA)O60885
IntAct (EBI)O60885
FunCoupENSG00000141867
BioGRIDBRD4
STRING (EMBL)BRD4
ZODIACBRD4
Ontologies - Pathways
QuickGOO60885
Ontology : AmiGOregulation of transcription involved in G1/S transition of mitotic cell cycle  condensed nuclear chromosome  RNA polymerase II core binding  p53 binding  chromatin binding  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  cellular response to DNA damage stimulus  positive regulation of G2/M transition of mitotic cell cycle  viral process  covalent chromatin modification  positive regulation of transcription elongation from RNA polymerase II promoter  positive regulation of transcription elongation from RNA polymerase II promoter  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of transcription from RNA polymerase II promoter  regulation of inflammatory response  lysine-acetylated histone binding  regulation of phosphorylation of RNA polymerase II C-terminal domain  
Ontology : EGO-EBIregulation of transcription involved in G1/S transition of mitotic cell cycle  condensed nuclear chromosome  RNA polymerase II core binding  p53 binding  chromatin binding  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  cellular response to DNA damage stimulus  positive regulation of G2/M transition of mitotic cell cycle  viral process  covalent chromatin modification  positive regulation of transcription elongation from RNA polymerase II promoter  positive regulation of transcription elongation from RNA polymerase II promoter  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of transcription from RNA polymerase II promoter  regulation of inflammatory response  lysine-acetylated histone binding  regulation of phosphorylation of RNA polymerase II C-terminal domain  
NDEx NetworkBRD4
Atlas of Cancer Signalling NetworkBRD4
Wikipedia pathwaysBRD4
Orthology - Evolution
OrthoDB23476
GeneTree (enSembl)ENSG00000141867
Phylogenetic Trees/Animal Genes : TreeFamBRD4
HOVERGENO60885
HOGENOMO60885
Homologs : HomoloGeneBRD4
Homology/Alignments : Family Browser (UCSC)BRD4
Gene fusions - Rearrangements
Fusion : MitelmanBRD4/NUTM1 [19p13.12/15q14]  
Fusion : MitelmanEPS15L1/BRD4 [19p13.11/19p13.12]  [t(19;19)(p13;p13)]  
Fusion : COSMICBRD4 [19p13.12]  -  C15orf55 [780]  [fusion_781]  [fusion_821]  [fusion_972]  
Fusion: TCGAEPS15L1 19p13.11 BRD4 19p13.12 BRCA
Fusion : TICdbNUTM1 [15q14]  -  BRD4 [19p13.12]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBRD4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BRD4
dbVarBRD4
ClinVarBRD4
1000_GenomesBRD4 
Exome Variant ServerBRD4
ExAC (Exome Aggregation Consortium)ENSG00000141867
GNOMAD BrowserENSG00000141867
Genetic variants : HAPMAP23476
Genomic Variants (DGV)BRD4 [DGVbeta]
DECIPHERBRD4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBRD4 
Mutations
ICGC Data PortalBRD4 
TCGA Data PortalBRD4 
Broad Tumor PortalBRD4
OASIS PortalBRD4 [ Somatic mutations - Copy number]
Cancer Gene: CensusBRD4 
Somatic Mutations in Cancer : COSMICBRD4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDBRD4
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch BRD4
DgiDB (Drug Gene Interaction Database)BRD4
DoCM (Curated mutations)BRD4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)BRD4 (select a term)
intoGenBRD4
NCG5 (London)BRD4
Cancer3DBRD4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608749   
Orphanet23447   
MedgenBRD4
Genetic Testing Registry BRD4
NextProtO60885 [Medical]
TSGene23476
GENETestsBRD4
Target ValidationBRD4
Huge Navigator BRD4 [HugePedia]
snp3D : Map Gene to Disease23476
BioCentury BCIQBRD4
ClinGenBRD4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23476
Chemical/Pharm GKB GenePA25416
Clinical trialBRD4
Miscellaneous
canSAR (ICR)BRD4 (select the gene name)
Probes
Litterature
PubMed162 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineBRD4
EVEXBRD4
GoPubMedBRD4
iHOPBRD4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Oct 12 16:17:35 CEST 2017

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