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O60885 (BRD4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Bromodomain-containing protein 4
Alternative name(s):
Protein HUNK1
Gene names
Name:BRD4
Synonyms:HUNK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1362 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in a process governing chromosomal dynamics during mitosis By similarity.

Subunit structure

Associated with chromosomes during mitosis By similarity. Interacts with bovine papillomavirus type 1 regulatory protein E2. Ref.6

Subcellular location

Nucleus By similarity.

Tissue specificity

Ubiquitously expressed. Ref.4

Involvement in disease

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. Ref.1 Ref.4

Sequence similarities

Contains 2 bromo domains.

Contains 1 NET domain.

Sequence caution

The sequence AAC27978.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DomainBromodomain
Repeat
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromosome segregation

Inferred from electronic annotation. Source: Compara

histone H3-K14 acetylation

Inferred from electronic annotation. Source: Compara

histone H4-K12 acetylation

Inferred from electronic annotation. Source: Compara

inner cell mass cell proliferation

Inferred from electronic annotation. Source: Compara

positive regulation of DNA binding

Inferred from electronic annotation. Source: Compara

positive regulation of G2/M transition of mitotic cell cycle

Inferred from mutant phenotype PubMed 10938129. Source: MGI

positive regulation of transcription elongation from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18039861. Source: MGI

protein phosphorylation

Inferred from electronic annotation. Source: Compara

regulation of transcription involved in G1 phase of mitotic cell cycle

Inferred from mutant phenotype PubMed 18039861. Source: MGI

virus-host interaction

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcondensed nuclear chromosome

Inferred from direct assay PubMed 10938129. Source: MGI

cytoplasm

Inferred from direct assay. Source: HPA

nuclear chromatin

Inferred from electronic annotation. Source: Compara

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: Compara

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GRB2P629932EBI-723869,EBI-401755
NCK1P163332EBI-723869,EBI-389883

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60885-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O60885-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     720-722: EMA → GPA
     723-1362: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13621362Bromodomain-containing protein 4
PRO_0000211183

Regions

Domain75 – 14773Bromo 1
Domain368 – 44073Bromo 2
Domain600 – 68283NET
Compositional bias535 – 59460Lys-rich
Compositional bias692 – 71726Ser-rich
Compositional bias703 – 71412Poly-Ser
Compositional bias738 – 7436Poly-His
Compositional bias757 – 7615Poly-Pro
Compositional bias764 – 7707Poly-Pro
Compositional bias771 – 7755Poly-Gln
Compositional bias776 – 7838Poly-Pro
Compositional bias954 – 96411Poly-Pro
Compositional bias974 – 98613Poly-Pro
Compositional bias1011 – 10144Poly-Pro
Compositional bias1028 – 10336Poly-Pro
Compositional bias1283 – 130018Poly-Gln
Compositional bias1301 – 13088Poly-Ala
Compositional bias1335 – 13384Poly-Arg

Sites

Site719 – 7202Breakpoint for translocation to form BDR4-NUT fusion protein

Amino acid modifications

Modified residue4701Phosphoserine Ref.7
Modified residue5981Phosphothreonine By similarity
Modified residue6011Phosphoserine Ref.9 Ref.11
Modified residue10451Phosphoserine By similarity
Modified residue11111N6-acetyllysine Ref.8
Modified residue11171Phosphoserine Ref.5 Ref.9 Ref.11

Natural variations

Alternative sequence720 – 7223EMA → GPA in isoform 2.
VSP_010902
Alternative sequence723 – 1362640Missing in isoform 2.
VSP_010903
Natural variant371P → S. Ref.12
Corresponds to variant rs35177876 [ dbSNP | Ensembl ].
VAR_041919
Natural variant3711A → G. Ref.12
Corresponds to variant rs55805532 [ dbSNP | Ensembl ].
VAR_041920
Natural variant5631S → N. Ref.12
Corresponds to variant rs55970906 [ dbSNP | Ensembl ].
VAR_041921
Natural variant5981T → S. Ref.12
Corresponds to variant rs34362023 [ dbSNP | Ensembl ].
VAR_041922
Natural variant6691R → H. Ref.12
Corresponds to variant rs35824241 [ dbSNP | Ensembl ].
VAR_041923
Natural variant10971R → H.
Corresponds to variant rs35676845 [ dbSNP | Ensembl ].
VAR_048427

Secondary structure

1 ....................................... 1362
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified January 31, 2002. Version 2.
Checksum: D52EFE1CF9960907

FASTA1,362152,219
        10         20         30         40         50         60 
MSAESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET SNPNKPKRQT 

        70         80         90        100        110        120 
NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI IKTPMDMGTI KKRLENNYYW 

       130        140        150        160        170        180 
NAQECIQDFN TMFTNCYIYN KPGDDIVLMA EALEKLFLQK INELPTEETE IMIVQAKGRG 

       190        200        210        220        230        240 
RGRKETGTAK PGVSTVPNTT QASTPPQTQT PQPNPPPVQA TPHPFPAVTP DLIVQTPVMT 

       250        260        270        280        290        300 
VVPPQPLQTP PPVPPQPQPP PAPAPQPVQS HPPIIAATPQ PVKTKKGVKR KADTTTPTTI 

       310        320        330        340        350        360 
DPIHEPPSLP PEPKTTKLGQ RRESSRPVKP PKKDVPDSQQ HPAPEKSSKV SEQLKCCSGI 

       370        380        390        400        410        420 
LKEMFAKKHA AYAWPFYKPV DVEALGLHDY CDIIKHPMDM STIKSKLEAR EYRDAQEFGA 

       430        440        450        460        470        480 
DVRLMFSNCY KYNPPDHEVV AMARKLQDVF EMRFAKMPDE PEEPVVAVSS PAVPPPTKVV 

       490        500        510        520        530        540 
APPSSSDSSS DSSSDSDSST DDSEEERAQR LAELQEQLKA VHEQLAALSQ PQQNKPKKKE 

       550        560        570        580        590        600 
KDKKEKKKEK HKRKEEVEEN KKSKAKEPPP KKTKKNNSSN SNVSKKEPAP MKSKPPPTYE 

       610        620        630        640        650        660 
SEEEDKCKPM SYEEKRQLSL DINKLPGEKL GRVVHIIQSR EPSLKNSNPD EIEIDFETLK 

       670        680        690        700        710        720 
PSTLRELERY VTSCLRKKRK PQAEKVDVIA GSSKMKGFSS SESESSSESS SSDSEDSETE 

       730        740        750        760        770        780 
MAPKSKKKGH PGREQKKHHH HHHQQMQQAP APVPQQPPPP PQQPPPPPPP QQQQQPPPPP 

       790        800        810        820        830        840 
PPPSMPQQAA PAMKSSPPPF IATQVPVLEP QLPGSVFDPI GHFTQPILHL PQPELPPHLP 

       850        860        870        880        890        900 
QPPEHSTPPH LNQHAVVSPP ALHNALPQQP SRPSNRAAAL PPKPARPPAV SPALTQTPLL 

       910        920        930        940        950        960 
PQPPMAQPPQ VLLEDEEPPA PPLTSMQMQL YLQQLQKVQP PTPLLPSVKV QSQPPPPLPP 

       970        980        990       1000       1010       1020 
PPHPSVQQQL QQQPPPPPPP QPQPPPQQQH QPPPRPVHLQ PMQFSTHIQQ PPPPQGQQPP 

      1030       1040       1050       1060       1070       1080 
HPPPGQQPPP PQPAKPQQVI QHHHSPRHHK SDPYSTGHLR EAPSPLMIHS PQMSQFQSLT 

      1090       1100       1110       1120       1130       1140 
HQSPPQQNVQ PKKQELRAAS VVQPQPLVVV KEEKIHSPII RSEPFSPSLR PEPPKHPESI 

      1150       1160       1170       1180       1190       1200 
KAPVHLPQRP EMKPVDVGRP VIRPPEQNAP PPGAPDKDKQ KQEPKTPVAP KKDLKIKNMG 

      1210       1220       1230       1240       1250       1260 
SWASLVQKHP TTPSSTAKSS SDSFEQFRRA AREKEEREKA LKAQAEHAEK EKERLRQERM 

      1270       1280       1290       1300       1310       1320 
RSREDEDALE QARRAHEEAR RRQEQQQQQR QEQQQQQQQQ AAAVAAAATP QAQSSQPQSM 

      1330       1340       1350       1360 
LDQQRELARK REQERRRREA MAATIDMNFQ SDLLSIFEEN LF

« Hide

Isoform 2 (Short) [UniParc].

Checksum: FF040EE016B37F87
Show »

FASTA72280,463

References

« Hide 'large scale' references
[1]"BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19)."
French C.A., Miyoshi I., Aster J.C., Kubonishi I., Kroll T.G., Dal Cin P., Vargas S.O., Perez-Atayde A.R., Fletcher J.A.
Am. J. Pathol. 159:1987-1992(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE, CHROMOSOMAL TRANSLOCATION WITH NUT.
[2]Weber B.
Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Placenta.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma."
French C.A., Miyoshi I., Kubonishi I., Grier H.E., Perez-Atayde A.R., Fletcher J.A.
Cancer Res. 63:304-307(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-719, DISEASE, CHROMOSOMAL TRANSLOCATION WITH NUT, TISSUE SPECIFICITY.
Tissue: Carcinoma.
[5]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1117, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[6]"ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance."
Parish J.L., Bean A.M., Park R.B., Androphy E.J.
Mol. Cell 24:867-876(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BOVINE PAPILLOMAVIRUS TYPE 1 REGULATORY PROTEIN E2.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[8]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1111, MASS SPECTROMETRY.
[9]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-601 AND SER-1117, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-601 AND SER-1117, MASS SPECTROMETRY.
[12]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-37; GLY-371; ASN-563; SER-598 AND HIS-669.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF386649 mRNA. Translation: AAL26987.1.
Y12059 mRNA. Translation: CAA72780.1.
AC004798 Genomic DNA. Translation: AAC27978.1. Different initiation.
AY166680 mRNA. Translation: AAO22237.1. Different termination.
IPIIPI00440727.
IPI00440728.
RefSeqNP_055114.1. NM_014299.2.
NP_490597.1. NM_058243.2.
UniGeneHs.187763.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2I8NNMR-A352-457[»]
2LSPNMR-B333-460[»]
2NNUX-ray1.59B1343-1362[»]
2OSSX-ray1.35A44-168[»]
2OUOX-ray1.89A333-460[»]
2YELX-ray1.65A44-168[»]
2YEMX-ray2.30A/B333-460[»]
3MXFX-ray1.60A44-168[»]
3P5OX-ray1.60A44-168[»]
3SVFX-ray1.98A44-168[»]
3SVGX-ray1.68A44-168[»]
3U5JX-ray1.60A44-168[»]
3U5KX-ray1.80A/B/C/D44-168[»]
3U5LX-ray1.39A44-168[»]
3UVWX-ray1.37A44-168[»]
3UVXX-ray1.91A44-168[»]
3UVYX-ray2.02A44-168[»]
3UW9X-ray2.30A/B/C/D44-168[»]
3ZYUX-ray1.50A/B44-168[»]
4A9LX-ray1.60A44-168[»]
4DONX-ray1.52A44-166[»]
4E96X-ray1.92A44-168[»]
4F3IX-ray1.40A44-168[»]
4GPJX-ray1.60A44-168[»]
4HBVX-ray1.63A44-168[»]
4HBWX-ray1.69A44-168[»]
4HBXX-ray1.62A44-168[»]
4HBYX-ray1.59A44-168[»]
4J0RX-ray1.72A44-168[»]
4J0SX-ray1.84A44-168[»]
ProteinModelPortalO60885.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-39776N.
IntActO60885. 9 interactions.
MINTMINT-1176376.
STRING9606.ENSP00000263377.

PTM databases

PhosphoSiteO60885.

Proteomic databases

PaxDbO60885.
PeptideAtlasO60885.
PRIDEO60885.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263377; ENSP00000263377; ENSG00000141867.
ENST00000371835; ENSP00000360901; ENSG00000141867.
GeneID23476.
KEGGhsa:23476.
UCSCuc002nar.3. human.
uc002nas.3. human.

Organism-specific databases

CTD23476.
GeneCardsGC19M015348.
HGNCHGNC:13575. BRD4.
HPAHPA015055.
MIM608749. gene.
neXtProtNX_O60885.
PharmGKBPA25416.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5076.
HOGENOMHOG000231200.
HOVERGENHBG004896.
InParanoidO60885.
KOK11722.
OMAPVIRPPE.
OrthoDBEOG45DWNS.

Gene expression databases

ArrayExpressO60885.
BgeeO60885.
CleanExHS_BRD4.
GenevestigatorO60885.
GermOnlineENSG00000141867. Homo sapiens.

Family and domain databases

Gene3D1.20.920.10. 2 hits.
InterProIPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamPF00439. Bromodomain. 2 hits.
[Graphical view]
PRINTSPR00503. BROMODOMAIN.
SMARTSM00297. BROMO. 2 hits.
[Graphical view]
SUPFAMSSF47370. Bromodomain. 2 hits.
PROSITEPS00633. BROMODOMAIN_1. 1 hit.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBO60885.
ChEMBLCHEMBL1163125.
ChiTaRSBRD4. human.
EvolutionaryTraceO60885.
GenomeRNAi23476.
NextBio45817.
PMAP-CutDBO60885.
SOURCESearch...

Entry information

Entry nameBRD4_HUMAN
AccessionPrimary (citable) accession number: O60885
Secondary accession number(s): O60433, Q86YS8, Q96PD3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 31, 2002
Last modified: May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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