Reviewed, UniProtKB/Swiss-Prot O60885 (BRD4_HUMAN)

Names and origin

Protein names

Recommended name:
    Bromodomain-containing protein 4
Alternative name(s):
    HUNK1 protein

Gene names

Name:	BRD4
Synonyms:	HUNK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1362 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
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.4 Ref.1
Sequence similarities	Contains 2 bromo domains.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Bromodomain Repeat
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-723869,EBI-886
E2	P03120	2	EBI-723869,EBI-1779322	From a different organism.
GRB2	P62993	1	EBI-723869,EBI-401755
NCK1	P16333	1	EBI-723869,EBI-389883
PIK3R1	P27986	1	EBI-723869,EBI-79464

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1362

1362

Bromodomain-containing protein 4

PRO_0000211183

Regions

Domain

75 – 147

73

Bromo 1

Domain

368 – 440

73

Bromo 2

Compositional bias

535 – 594

60

Lys-rich

Compositional bias

692 – 717

26

Ser-rich

Compositional bias

703 – 714

12

Poly-Ser

Compositional bias

738 – 743

6

Poly-His

Compositional bias

757 – 761

5

Poly-Pro

Compositional bias

764 – 770

7

Poly-Pro

Compositional bias

771 – 775

5

Poly-Gln

Compositional bias

776 – 783

8

Poly-Pro

Compositional bias

954 – 964

11

Poly-Pro

Compositional bias

974 – 986

13

Poly-Pro

Compositional bias

1011 – 1014

4

Poly-Pro

Compositional bias

1028 – 1033

6

Poly-Pro

Compositional bias

1283 – 1300

18

Poly-Gln

Compositional bias

1301 – 1308

8

Poly-Ala

Compositional bias

1335 – 1338

4

Poly-Arg

Sites

Site

719 – 720

2

Breakpoint for translocation to form BDR4-NUT fusion protein

Amino acid modifications

Modified residue

470

1

Phosphoserine Ref.5 Ref.10

Modified residue

601

1

Phosphoserine Ref.8

Modified residue

1045

1

Phosphoserine Ref.6

Modified residue

1117

1

Phosphoserine Ref.10 Ref.6 Ref.7 Ref.9

Natural variations

Alternative sequence

720 – 722

3

EMA → GPA in isoform 2.

VSP_010902

Alternative sequence

723 – 1362

640

Missing in isoform 2.

VSP_010903

Natural variant

37

1

P → S Ref.12

VAR_041919

Natural variant

371

1

A → G Ref.12

VAR_041920

Natural variant

563

1

S → N Ref.12

VAR_041921

Natural variant

598

1

T → S Ref.12

VAR_041922

Natural variant

669

1

R → H Ref.12

VAR_041923

Natural variant

1097

1

R → H: dbSNP rs35676845.

VAR_048427

Secondary structure

1

.

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.

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.

.

.

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.

.

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.

.

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1362

Helix Strand Turn

Details...

Helix

61 – 68

8

Helix

70 – 75

6

Helix

81 – 83

3

Turn

89 – 93

5

Helix

97 – 100

4

Helix

107 – 115

9

Helix

122 – 139

18

Helix

145 – 161

17

Helix

350 – 364

15

Helix

367 – 369

3

Helix

370 – 373

4

Helix

374 – 376

3

Helix

390 – 393

4

Helix

400 – 408

9

Helix

415 – 432

18

Helix

438 – 455

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified January 31, 2002. Version 2. Checksum: D52EFE1CF9960907	FASTA	1,362	152,219
	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
	Isoform 2 (Short). Checksum: FF040EE016B37F87	FASTA	722	80,463
	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 SSDSEDSETG PA

References

	« Hide 'large scale' referencesShow '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: 11733348] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DISEASE, CHROMOSOMAL TRANSLOCATION.
[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. , 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: 15057824] [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: 12543779] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-719, DISEASE, CHROMOSOMAL TRANSLOCATION WITH NUT, TISSUE SPECIFICITY. Tissue: Carcinoma.
[5]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"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: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1045 AND SER-1117, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1117, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-601, MASS SPECTROMETRY.
[9]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1117, MASS SPECTROMETRY.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470 AND SER-1117, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], 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. , 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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-37; GLY-371; ASN-563; SER-598 AND HIS-669.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00440727.
IPI00440728.

RefSeq

NP_055114.1.
NP_490597.1.

UniGene

Hs.187763

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I8N	NMR	-	A	352-457	[»]
2NNU	X-ray	1.59	B	1343-1362	[»]
2OSS	X-ray	1.35	A	44-168	[»]
2OUO	X-ray	1.89	A	333-460	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O60885. 10 interactions.

PTM databases

PhosphoSite

O60885.

Proteomic databases

PeptideAtlas

O60885.

PRIDE

O60885.

Genome annotation databases

Ensembl

ENSG00000141867. Homo sapiens. [Contig view]

GeneID

23476.

KEGG

hsa:23476.

Organism-specific databases

GeneCards

GC19M015209.

H-InvDB

HIX0001212.
HIX0040004.

HGNC

HGNC:13575. BRD4.

HPA

HPA015055.

MIM

608749. gene.

PharmGKB

PA25416.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O60885.

HOVERGEN

O60885.

OMA

O60885. PPALHNA.

Gene expression databases

ArrayExpress

O60885.

Bgee

O60885.

CleanEx

HS_BRD4.

GermOnline

ENSG00000141867. Homo sapiens.

Family and domain databases

InterPro

IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
[Graphical view]

Gene3D

G3DSA:1.20.920.10. Bromodomain. 2 hits.

Pfam

PF00439. Bromodomain. 2 hits.
[Graphical view]

PRINTS

PR00503. BROMODOMAIN.

SMART

SM00297. BROMO. 2 hits.
[Graphical view]

PROSITE

PS00633. BROMODOMAIN_1. 1 hit.
PS50014. BROMODOMAIN_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

45817.

PMAP-CutDB

O60885.

SOURCE

Search...

Entry information

Entry name

BRD4_HUMAN

Accession

Primary (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:	June 16, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)