Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

O60885

- BRD4_HUMAN

UniProt

O60885 - BRD4_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Bromodomain-containing protein 4

Gene

BRD4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei140 – 1401Acetylated histones1 Publication
Binding sitei140 – 1401Inhibitor
Binding sitei433 – 4331Acetylated histones1 Publication
Binding sitei433 – 4331Inhibitor
Sitei719 – 7202Breakpoint for translocation to form BDR4-NUT fusion protein

GO - Molecular functioni

  1. chromatin binding Source: UniProtKB
  2. DNA binding Source: Ensembl
  3. lysine-acetylated histone binding Source: UniProtKB
  4. p53 binding Source: UniProtKB

GO - Biological processi

  1. cellular response to DNA damage stimulus Source: UniProtKB-KW
  2. chromatin remodeling Source: UniProtKB
  3. chromosome segregation Source: Ensembl
  4. histone H3-K14 acetylation Source: Ensembl
  5. histone H4-K12 acetylation Source: Ensembl
  6. inner cell mass cell proliferation Source: Ensembl
  7. negative regulation of DNA damage checkpoint Source: UniProtKB
  8. positive regulation of DNA binding Source: Ensembl
  9. positive regulation of G2/M transition of mitotic cell cycle Source: MGI
  10. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  11. positive regulation of transcription elongation from RNA polymerase II promoter Source: UniProtKB
  12. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  13. protein phosphorylation Source: Ensembl
  14. regulation of inflammatory response Source: UniProtKB
  15. regulation of phosphorylation of RNA polymerase II C-terminal domain Source: UniProtKB
  16. regulation of transcription involved in G1/S transition of mitotic cell cycle Source: MGI
  17. transcription, DNA-templated Source: UniProtKB-KW
  18. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Biological processi

DNA damage, Host-virus interaction, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Bromodomain-containing protein 4
Alternative name(s):
Protein HUNK1
Gene namesi
Name:BRD4
Synonyms:HUNK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:13575. BRD4.

Subcellular locationi

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.

GO - Cellular componenti

  1. chromosome Source: UniProtKB
  2. condensed nuclear chromosome Source: MGI
  3. cytoplasm Source: HPA
  4. nuclear chromatin Source: Ensembl
  5. nucleus Source: UniProtKB
  6. positive transcription elongation factor complex b Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi140 – 1401N → A: Abolishes binding to acetylated histones. 2 Publications
Mutagenesisi433 – 4331N → A: Abolishes binding to acetylated histones. 1 Publication
Mutagenesisi492 – 4943SSS → ASA: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication
Mutagenesisi498 – 5003SST → AAA: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication
Mutagenesisi503 – 5031S → A: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication

Organism-specific databases

PharmGKBiPA25416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 13621362Bromodomain-containing protein 4PRO_0000211183Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei470 – 4701Phosphoserine1 Publication
Modified residuei484 – 4841Phosphoserine; by CK21 Publication
Modified residuei488 – 4881Phosphoserine; by CK21 Publication
Modified residuei492 – 4921Phosphoserine; by CK21 Publication
Modified residuei494 – 4941Phosphoserine; by CK21 Publication
Modified residuei498 – 4981Phosphoserine; by CK21 Publication
Modified residuei499 – 4991Phosphoserine; by CK21 Publication
Modified residuei503 – 5031Phosphoserine; by CK21 Publication
Modified residuei601 – 6011Phosphoserine2 Publications
Modified residuei1111 – 11111N6-acetyllysine1 Publication
Modified residuei1117 – 11171Phosphoserine3 Publications

Post-translational modificationi

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.6 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO60885.
PaxDbiO60885.
PeptideAtlasiO60885.
PRIDEiO60885.

PTM databases

PhosphoSiteiO60885.

Miscellaneous databases

PMAP-CutDBO60885.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiO60885.
CleanExiHS_BRD4.
ExpressionAtlasiO60885. baseline and differential.
GenevestigatoriO60885.

Organism-specific databases

HPAiHPA015055.

Interactioni

Subunit structurei

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 EBNA1.17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
E2P031203EBI-723869,EBI-1779322From a different organism.
E2P040152EBI-723869,EBI-7010556From a different organism.
E2P173832EBI-723869,EBI-7010529From a different organism.
GRB2P629932EBI-723869,EBI-401755
JMJD6Q6NYC110EBI-723869,EBI-8464037
NCK1P163332EBI-723869,EBI-389883

Protein-protein interaction databases

BioGridi117036. 43 interactions.
DIPiDIP-39776N.
IntActiO60885. 21 interactions.
MINTiMINT-1176376.
STRINGi9606.ENSP00000263377.

Structurei

Secondary structure

1
1362
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi53 – 553Combined sources
Helixi61 – 688Combined sources
Helixi70 – 756Combined sources
Helixi81 – 833Combined sources
Helixi89 – 924Combined sources
Helixi97 – 1004Combined sources
Helixi107 – 1159Combined sources
Helixi122 – 13918Combined sources
Helixi145 – 16117Combined sources
Beta strandi342 – 3465Combined sources
Helixi350 – 36415Combined sources
Helixi367 – 3693Combined sources
Helixi370 – 3734Combined sources
Helixi374 – 3763Combined sources
Helixi382 – 3854Combined sources
Helixi390 – 3934Combined sources
Helixi400 – 4089Combined sources
Beta strandi412 – 4143Combined sources
Helixi415 – 43218Combined sources
Beta strandi435 – 4373Combined sources
Helixi438 – 45518Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I8NNMR-A352-457[»]
2LSPNMR-B333-460[»]
2MJVNMR-B333-460[»]
2NNUX-ray1.59B1343-1362[»]
2OSSX-ray1.35A44-168[»]
2OUOX-ray1.89A333-460[»]
2YELX-ray1.65A44-168[»]
2YEMX-ray2.30A/B333-460[»]
3MXFX-ray1.60A42-168[»]
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[»]
4BJXX-ray1.59A44-168[»]
4BW1X-ray1.40A44-168[»]
4BW2X-ray1.92A44-168[»]
4BW3X-ray1.50A44-168[»]
4BW4X-ray1.67A44-168[»]
4C66X-ray1.87A44-167[»]
4C67X-ray1.55A44-168[»]
4CFKX-ray1.55A44-168[»]
4CFLX-ray1.32A44-168[»]
4DONX-ray1.52A44-166[»]
4E96X-ray1.92A44-168[»]
4F3IX-ray1.40A44-168[»]
4GPJX-ray1.60A44-168[»]
4HBVX-ray1.63A42-168[»]
4HBWX-ray1.69A42-168[»]
4HBXX-ray1.62A42-168[»]
4HBYX-ray1.59A44-168[»]
4HXKX-ray1.61A44-167[»]
4HXLX-ray1.52A44-167[»]
4HXMX-ray1.50A44-166[»]
4HXNX-ray1.49A44-167[»]
4HXOX-ray1.76A44-167[»]
4HXPX-ray1.73A44-166[»]
4HXRX-ray1.53A44-167[»]
4HXSX-ray1.43A44-166[»]
4IOOX-ray1.25A44-168[»]
4IOQX-ray1.50A44-168[»]
4IORX-ray1.40A44-168[»]
4J0RX-ray1.72A44-168[»]
4J0SX-ray1.84A44-168[»]
4J3IX-ray1.24A44-168[»]
4KV1X-ray1.50A/B41-168[»]
4KV4X-ray2.00A351-459[»]
4LR6X-ray1.29A42-168[»]
4LRGX-ray2.21A42-168[»]
4LYIX-ray1.30A44-168[»]
4LYSX-ray1.83A44-168[»]
4LYWX-ray1.95A44-168[»]
4LZRX-ray1.85A44-168[»]
4LZSX-ray2.20A44-168[»]
4MENX-ray1.81A44-168[»]
4MEOX-ray1.72A44-168[»]
4MEPX-ray1.85A44-168[»]
4MEQX-ray1.77A44-168[»]
4MR3X-ray1.68A44-168[»]
4MR4X-ray1.66A44-168[»]
4NQMX-ray1.58A44-168[»]
4NR8X-ray1.64A44-168[»]
4NUCX-ray1.40A44-168[»]
4NUDX-ray1.20A44-168[»]
4NUEX-ray1.30A44-168[»]
4O70X-ray1.55A/B44-168[»]
4O71X-ray1.36A/B44-168[»]
4O72X-ray1.40A44-168[»]
4O74X-ray1.45A/B44-168[»]
4O75X-ray1.55A44-168[»]
4O76X-ray1.70A/B/C/D44-168[»]
4O77X-ray2.00A/B44-168[»]
4O78X-ray1.34A44-168[»]
4O7AX-ray1.34A44-168[»]
4O7BX-ray1.50A44-168[»]
4O7CX-ray1.55A44-168[»]
4O7EX-ray1.85A/B44-168[»]
4O7FX-ray1.80A/B44-168[»]
4OGIX-ray1.73A/B44-168[»]
4OGJX-ray1.65A/B44-168[»]
4PCEX-ray1.29A44-168[»]
4PCIX-ray1.25A44-168[»]
4PS5X-ray1.40A/B44-168[»]
4UYDX-ray1.37A44-183[»]
ProteinModelPortaliO60885.
SMRiO60885. Positions 44-166, 322-459, 605-682.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60885.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 14773Bromo 1PROSITE-ProRule annotationAdd
BLAST
Domaini368 – 44073Bromo 2PROSITE-ProRule annotationAdd
BLAST
Domaini600 – 68283NETPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni484 – 50320NPS regionAdd
BLAST
Regioni524 – 57956BID regionAdd
BLAST
Regioni1047 – 1362316C-terminal (CTD) regionAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi535 – 59460Lys-richAdd
BLAST
Compositional biasi692 – 71726Ser-richAdd
BLAST
Compositional biasi703 – 71412Poly-SerAdd
BLAST
Compositional biasi738 – 7436Poly-His
Compositional biasi757 – 7615Poly-Pro
Compositional biasi764 – 7707Poly-Pro
Compositional biasi771 – 7755Poly-Gln
Compositional biasi776 – 7838Poly-Pro
Compositional biasi954 – 96411Poly-ProAdd
BLAST
Compositional biasi974 – 98613Poly-ProAdd
BLAST
Compositional biasi1011 – 10144Poly-Pro
Compositional biasi1028 – 10336Poly-Pro
Compositional biasi1283 – 130018Poly-GlnAdd
BLAST
Compositional biasi1301 – 13088Poly-Ala
Compositional biasi1335 – 13384Poly-Arg

Domaini

The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5).1 Publication
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).3 Publications
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).6 Publications

Sequence similaritiesi

Contains 2 bromo domains.PROSITE-ProRule annotation
Contains 1 NET domain.PROSITE-ProRule annotation

Keywords - Domaini

Bromodomain, Repeat

Phylogenomic databases

eggNOGiCOG5076.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiO60885.
KOiK11722.
OMAiFIATQVP.
PhylomeDBiO60885.
TreeFamiTF317345.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF00439. Bromodomain. 2 hits.
[Graphical view]
PRINTSiPR00503. BROMODOMAIN.
SMARTiSM00297. BROMO. 2 hits.
[Graphical view]
SUPFAMiSSF47370. SSF47370. 2 hits.
PROSITEiPS00633. BROMODOMAIN_1. 1 hit.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform A (identifier: O60885-1) [UniParc]FASTAAdd to Basket

Also known as: Brd4L, 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.

« Hide

        10         20         30         40         50
MSAESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET
60 70 80 90 100
SNPNKPKRQT NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI
110 120 130 140 150
IKTPMDMGTI KKRLENNYYW NAQECIQDFN TMFTNCYIYN KPGDDIVLMA
160 170 180 190 200
EALEKLFLQK INELPTEETE IMIVQAKGRG RGRKETGTAK PGVSTVPNTT
210 220 230 240 250
QASTPPQTQT PQPNPPPVQA TPHPFPAVTP DLIVQTPVMT VVPPQPLQTP
260 270 280 290 300
PPVPPQPQPP PAPAPQPVQS HPPIIAATPQ PVKTKKGVKR KADTTTPTTI
310 320 330 340 350
DPIHEPPSLP PEPKTTKLGQ RRESSRPVKP PKKDVPDSQQ HPAPEKSSKV
360 370 380 390 400
SEQLKCCSGI LKEMFAKKHA AYAWPFYKPV DVEALGLHDY CDIIKHPMDM
410 420 430 440 450
STIKSKLEAR EYRDAQEFGA DVRLMFSNCY KYNPPDHEVV AMARKLQDVF
460 470 480 490 500
EMRFAKMPDE PEEPVVAVSS PAVPPPTKVV APPSSSDSSS DSSSDSDSST
510 520 530 540 550
DDSEEERAQR LAELQEQLKA VHEQLAALSQ PQQNKPKKKE KDKKEKKKEK
560 570 580 590 600
HKRKEEVEEN KKSKAKEPPP KKTKKNNSSN SNVSKKEPAP MKSKPPPTYE
610 620 630 640 650
SEEEDKCKPM SYEEKRQLSL DINKLPGEKL GRVVHIIQSR EPSLKNSNPD
660 670 680 690 700
EIEIDFETLK PSTLRELERY VTSCLRKKRK PQAEKVDVIA GSSKMKGFSS
710 720 730 740 750
SESESSSESS SSDSEDSETE MAPKSKKKGH PGREQKKHHH HHHQQMQQAP
760 770 780 790 800
APVPQQPPPP PQQPPPPPPP QQQQQPPPPP PPPSMPQQAA PAMKSSPPPF
810 820 830 840 850
IATQVPVLEP QLPGSVFDPI GHFTQPILHL PQPELPPHLP QPPEHSTPPH
860 870 880 890 900
LNQHAVVSPP ALHNALPQQP SRPSNRAAAL PPKPARPPAV SPALTQTPLL
910 920 930 940 950
PQPPMAQPPQ VLLEDEEPPA PPLTSMQMQL YLQQLQKVQP PTPLLPSVKV
960 970 980 990 1000
QSQPPPPLPP PPHPSVQQQL QQQPPPPPPP QPQPPPQQQH QPPPRPVHLQ
1010 1020 1030 1040 1050
PMQFSTHIQQ PPPPQGQQPP HPPPGQQPPP PQPAKPQQVI QHHHSPRHHK
1060 1070 1080 1090 1100
SDPYSTGHLR EAPSPLMIHS PQMSQFQSLT HQSPPQQNVQ PKKQELRAAS
1110 1120 1130 1140 1150
VVQPQPLVVV KEEKIHSPII RSEPFSPSLR PEPPKHPESI KAPVHLPQRP
1160 1170 1180 1190 1200
EMKPVDVGRP VIRPPEQNAP PPGAPDKDKQ KQEPKTPVAP KKDLKIKNMG
1210 1220 1230 1240 1250
SWASLVQKHP TTPSSTAKSS SDSFEQFRRA AREKEEREKA LKAQAEHAEK
1260 1270 1280 1290 1300
EKERLRQERM RSREDEDALE QARRAHEEAR RRQEQQQQQR QEQQQQQQQQ
1310 1320 1330 1340 1350
AAAVAAAATP QAQSSQPQSM LDQQRELARK REQERRRREA MAATIDMNFQ
1360
SDLLSIFEEN LF
Length:1,362
Mass (Da):152,219
Last modified:January 31, 2002 - v2
Checksum:iD52EFE1CF9960907
GO
Isoform C (identifier: O60885-2) [UniParc]FASTAAdd to Basket

Also known as: Brd4S, Short

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

Show »
Length:722
Mass (Da):80,463
Checksum:iFF040EE016B37F87
GO
Isoform B (identifier: O60885-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     720-1362: EMAPKSKKKG...LLSIFEENLF → AFCTSGDFVS...ECARCCVGCS

Note: Does not contain the C-terminal (CTD) region required to recruit the P-TEFb complex.

Show »
Length:794
Mass (Da):88,289
Checksum:iACB01CC53AA4C431
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371P → S.1 Publication
Corresponds to variant rs35177876 [ dbSNP | Ensembl ].
VAR_041919
Natural varianti371 – 3711A → G.1 Publication
Corresponds to variant rs55805532 [ dbSNP | Ensembl ].
VAR_041920
Natural varianti563 – 5631S → N.1 Publication
Corresponds to variant rs55970906 [ dbSNP | Ensembl ].
VAR_041921
Natural varianti598 – 5981T → S.1 Publication
Corresponds to variant rs34362023 [ dbSNP | Ensembl ].
VAR_041922
Natural varianti669 – 6691R → H.1 Publication
Corresponds to variant rs35824241 [ dbSNP | Ensembl ].
VAR_041923
Natural varianti1097 – 10971R → H.
Corresponds to variant rs35676845 [ dbSNP | Ensembl ].
VAR_048427

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei720 – 1362643EMAPK…EENLF → AFCTSGDFVSPGPSPYHSHV QCGRFREMLRWFLVDVEQTA AGQPHRQSAAGPAITWAPAI AYPSPECARCCVGCS in isoform B. 1 PublicationVSP_047671Add
BLAST
Alternative sequencei720 – 7223EMA → GPA in isoform C. 1 PublicationVSP_010902
Alternative sequencei723 – 1362640Missing in isoform C. 1 PublicationVSP_010903Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF386649 mRNA. Translation: AAL26987.1.
Y12059 mRNA. Translation: CAA72780.1.
AC004798 Genomic DNA. Translation: AAC27978.1. Different initiation.
AC003111 Genomic DNA. No translation available.
AC005776 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84470.1.
BC035266 mRNA. Translation: AAH35266.1.
AY166680 mRNA. Translation: AAO22237.1. Different termination.
CCDSiCCDS12328.1. [O60885-1]
CCDS46004.1. [O60885-2]
RefSeqiNP_055114.1. NM_014299.2. [O60885-2]
NP_490597.1. NM_058243.2. [O60885-1]
UniGeneiHs.187763.

Genome annotation databases

EnsembliENST00000263377; ENSP00000263377; ENSG00000141867. [O60885-1]
ENST00000360016; ENSP00000353112; ENSG00000141867. [O60885-3]
ENST00000371835; ENSP00000360901; ENSG00000141867. [O60885-2]
GeneIDi23476.
KEGGihsa:23476.
UCSCiuc002nar.3. human. [O60885-1]
uc002nas.3. human. [O60885-2]
uc002nat.3. human.

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF386649 mRNA. Translation: AAL26987.1 .
Y12059 mRNA. Translation: CAA72780.1 .
AC004798 Genomic DNA. Translation: AAC27978.1 . Different initiation.
AC003111 Genomic DNA. No translation available.
AC005776 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84470.1 .
BC035266 mRNA. Translation: AAH35266.1 .
AY166680 mRNA. Translation: AAO22237.1 . Different termination.
CCDSi CCDS12328.1. [O60885-1 ]
CCDS46004.1. [O60885-2 ]
RefSeqi NP_055114.1. NM_014299.2. [O60885-2 ]
NP_490597.1. NM_058243.2. [O60885-1 ]
UniGenei Hs.187763.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2I8N NMR - A 352-457 [» ]
2LSP NMR - B 333-460 [» ]
2MJV NMR - B 333-460 [» ]
2NNU X-ray 1.59 B 1343-1362 [» ]
2OSS X-ray 1.35 A 44-168 [» ]
2OUO X-ray 1.89 A 333-460 [» ]
2YEL X-ray 1.65 A 44-168 [» ]
2YEM X-ray 2.30 A/B 333-460 [» ]
3MXF X-ray 1.60 A 42-168 [» ]
3P5O X-ray 1.60 A 44-168 [» ]
3SVF X-ray 1.98 A 44-168 [» ]
3SVG X-ray 1.68 A 44-168 [» ]
3U5J X-ray 1.60 A 44-168 [» ]
3U5K X-ray 1.80 A/B/C/D 44-168 [» ]
3U5L X-ray 1.39 A 44-168 [» ]
3UVW X-ray 1.37 A 44-168 [» ]
3UVX X-ray 1.91 A 44-168 [» ]
3UVY X-ray 2.02 A 44-168 [» ]
3UW9 X-ray 2.30 A/B/C/D 44-168 [» ]
3ZYU X-ray 1.50 A/B 44-168 [» ]
4A9L X-ray 1.60 A 44-168 [» ]
4BJX X-ray 1.59 A 44-168 [» ]
4BW1 X-ray 1.40 A 44-168 [» ]
4BW2 X-ray 1.92 A 44-168 [» ]
4BW3 X-ray 1.50 A 44-168 [» ]
4BW4 X-ray 1.67 A 44-168 [» ]
4C66 X-ray 1.87 A 44-167 [» ]
4C67 X-ray 1.55 A 44-168 [» ]
4CFK X-ray 1.55 A 44-168 [» ]
4CFL X-ray 1.32 A 44-168 [» ]
4DON X-ray 1.52 A 44-166 [» ]
4E96 X-ray 1.92 A 44-168 [» ]
4F3I X-ray 1.40 A 44-168 [» ]
4GPJ X-ray 1.60 A 44-168 [» ]
4HBV X-ray 1.63 A 42-168 [» ]
4HBW X-ray 1.69 A 42-168 [» ]
4HBX X-ray 1.62 A 42-168 [» ]
4HBY X-ray 1.59 A 44-168 [» ]
4HXK X-ray 1.61 A 44-167 [» ]
4HXL X-ray 1.52 A 44-167 [» ]
4HXM X-ray 1.50 A 44-166 [» ]
4HXN X-ray 1.49 A 44-167 [» ]
4HXO X-ray 1.76 A 44-167 [» ]
4HXP X-ray 1.73 A 44-166 [» ]
4HXR X-ray 1.53 A 44-167 [» ]
4HXS X-ray 1.43 A 44-166 [» ]
4IOO X-ray 1.25 A 44-168 [» ]
4IOQ X-ray 1.50 A 44-168 [» ]
4IOR X-ray 1.40 A 44-168 [» ]
4J0R X-ray 1.72 A 44-168 [» ]
4J0S X-ray 1.84 A 44-168 [» ]
4J3I X-ray 1.24 A 44-168 [» ]
4KV1 X-ray 1.50 A/B 41-168 [» ]
4KV4 X-ray 2.00 A 351-459 [» ]
4LR6 X-ray 1.29 A 42-168 [» ]
4LRG X-ray 2.21 A 42-168 [» ]
4LYI X-ray 1.30 A 44-168 [» ]
4LYS X-ray 1.83 A 44-168 [» ]
4LYW X-ray 1.95 A 44-168 [» ]
4LZR X-ray 1.85 A 44-168 [» ]
4LZS X-ray 2.20 A 44-168 [» ]
4MEN X-ray 1.81 A 44-168 [» ]
4MEO X-ray 1.72 A 44-168 [» ]
4MEP X-ray 1.85 A 44-168 [» ]
4MEQ X-ray 1.77 A 44-168 [» ]
4MR3 X-ray 1.68 A 44-168 [» ]
4MR4 X-ray 1.66 A 44-168 [» ]
4NQM X-ray 1.58 A 44-168 [» ]
4NR8 X-ray 1.64 A 44-168 [» ]
4NUC X-ray 1.40 A 44-168 [» ]
4NUD X-ray 1.20 A 44-168 [» ]
4NUE X-ray 1.30 A 44-168 [» ]
4O70 X-ray 1.55 A/B 44-168 [» ]
4O71 X-ray 1.36 A/B 44-168 [» ]
4O72 X-ray 1.40 A 44-168 [» ]
4O74 X-ray 1.45 A/B 44-168 [» ]
4O75 X-ray 1.55 A 44-168 [» ]
4O76 X-ray 1.70 A/B/C/D 44-168 [» ]
4O77 X-ray 2.00 A/B 44-168 [» ]
4O78 X-ray 1.34 A 44-168 [» ]
4O7A X-ray 1.34 A 44-168 [» ]
4O7B X-ray 1.50 A 44-168 [» ]
4O7C X-ray 1.55 A 44-168 [» ]
4O7E X-ray 1.85 A/B 44-168 [» ]
4O7F X-ray 1.80 A/B 44-168 [» ]
4OGI X-ray 1.73 A/B 44-168 [» ]
4OGJ X-ray 1.65 A/B 44-168 [» ]
4PCE X-ray 1.29 A 44-168 [» ]
4PCI X-ray 1.25 A 44-168 [» ]
4PS5 X-ray 1.40 A/B 44-168 [» ]
4UYD X-ray 1.37 A 44-183 [» ]
ProteinModelPortali O60885.
SMRi O60885. Positions 44-166, 322-459, 605-682.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 117036. 43 interactions.
DIPi DIP-39776N.
IntActi O60885. 21 interactions.
MINTi MINT-1176376.
STRINGi 9606.ENSP00000263377.

Chemistry

BindingDBi O60885.
ChEMBLi CHEMBL1163125.
GuidetoPHARMACOLOGYi 1945.

PTM databases

PhosphoSitei O60885.

Proteomic databases

MaxQBi O60885.
PaxDbi O60885.
PeptideAtlasi O60885.
PRIDEi O60885.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000263377 ; ENSP00000263377 ; ENSG00000141867 . [O60885-1 ]
ENST00000360016 ; ENSP00000353112 ; ENSG00000141867 . [O60885-3 ]
ENST00000371835 ; ENSP00000360901 ; ENSG00000141867 . [O60885-2 ]
GeneIDi 23476.
KEGGi hsa:23476.
UCSCi uc002nar.3. human. [O60885-1 ]
uc002nas.3. human. [O60885-2 ]
uc002nat.3. human.

Organism-specific databases

CTDi 23476.
GeneCardsi GC19M015348.
HGNCi HGNC:13575. BRD4.
HPAi HPA015055.
MIMi 608749. gene.
neXtProti NX_O60885.
PharmGKBi PA25416.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5076.
GeneTreei ENSGT00760000119206.
HOGENOMi HOG000231200.
HOVERGENi HBG004896.
InParanoidi O60885.
KOi K11722.
OMAi FIATQVP.
PhylomeDBi O60885.
TreeFami TF317345.

Miscellaneous databases

ChiTaRSi BRD4. human.
EvolutionaryTracei O60885.
GeneWikii BRD4.
GenomeRNAii 23476.
NextBioi 45817.
PMAP-CutDB O60885.
PROi O60885.
SOURCEi Search...

Gene expression databases

Bgeei O60885.
CleanExi HS_BRD4.
ExpressionAtlasi O60885. baseline and differential.
Genevestigatori O60885.

Family and domain databases

Gene3Di 1.20.920.10. 2 hits.
InterProi IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view ]
Pfami PF00439. Bromodomain. 2 hits.
[Graphical view ]
PRINTSi PR00503. BROMODOMAIN.
SMARTi SM00297. BROMO. 2 hits.
[Graphical view ]
SUPFAMi SSF47370. SSF47370. 2 hits.
PROSITEi PS00633. BROMODOMAIN_1. 1 hit.
PS50014. BROMODOMAIN_2. 2 hits.
PS51525. NET. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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 A), DISEASE, CHROMOSOMAL TRANSLOCATION WITH NUT.
  2. Weber B.
    Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
    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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
    Tissue: Testis.
  6. "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.
  7. "The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription."
    Jang M.K., Mochizuki K., Zhou M., Jeong H.S., Brady J.N., Ozato K.
    Mol. Cell 19:523-534(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CDK9 AND CCNT1, IDENTIFICATION IN THE P-TEFB COMPLEX, SUBCELLULAR LOCATION.
  8. "Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4."
    Yang Z., Yik J.H., Chen R., He N., Jang M.K., Ozato K., Zhou Q.
    Mol. Cell 19:535-545(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CDK9 AND CCNT1, IDENTIFICATION IN THE P-TEFB COMPLEX.
  9. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. "Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes."
    You J., Srinivasan V., Denis G.V., Harrington W.J. Jr., Ballestas M.E., Kaye K.M., Howley P.M.
    J. Virol. 80:8909-8919(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KSHV PROTEIN LANA.
  11. "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.
  12. "The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4."
    Lin A., Wang S., Nguyen T., Shire K., Frappier L.
    J. Virol. 82:12009-12019(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPSTEIN-BARR VIRUS PROTEIN EBNA1.
  13. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-470, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  14. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. "Control of inducible gene expression by signal-dependent transcriptional elongation."
    Hargreaves D.C., Horng T., Medzhitov R.
    Cell 138:129-145(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  16. "Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA."
    Huang B., Yang X.D., Zhou M.M., Ozato K., Chen L.F.
    Mol. Cell. Biol. 29:1375-1387(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RELA.
  17. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  18. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3."
    Rahman S., Sowa M.E., Ottinger M., Smith J.A., Shi Y., Harper J.W., Howley P.M.
    Mol. Cell. Biol. 31:2641-2652(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WHSC1L1; JMJD6; CHD4; GLTSCR1 AND ATAD5.
  21. "Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin targeting to transcriptional regulation."
    Ai N., Hu X., Ding F., Yu B., Wang H., Lu X., Zhang K., Li Y., Han A., Lin W., Liu R., Chen R.
    Nucleic Acids Res. 39:9592-9604(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  22. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Bromodomain protein Brd4 associated with acetylated chromatin is important for maintenance of higher-order chromatin structure."
    Wang R., Li Q., Helfer C.M., Jiao J., You J.
    J. Biol. Chem. 287:10738-10752(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  24. "Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells."
    Zhang W., Prakash C., Sum C., Gong Y., Li Y., Kwok J.J., Thiessen N., Pettersson S., Jones S.J., Knapp S., Yang H., Chin K.C.
    J. Biol. Chem. 287:43137-43155(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  25. "BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain."
    Devaiah B.N., Lewis B.A., Cherman N., Hewitt M.C., Albrecht B.K., Robey P.G., Ozato K., Sims R.J. III, Singer D.S.
    Proc. Natl. Acad. Sci. U.S.A. 109:6927-6932(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  26. "Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting."
    Wu S.Y., Lee A.Y., Lai H.T., Zhang H., Chiang C.M.
    Mol. Cell 49:843-857(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TP53, PHOSPHORYLATION AT SER-484; SER-488; SER-492; SER-494; SER-498; SER-499 AND SER-503, MUTAGENESIS OF 492-SER--SER-494; 498-SER--THR-500 AND SER-503.
  27. "BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes."
    Patel M.C., Debrosse M., Smith M., Dey A., Huynh W., Sarai N., Heightman T.D., Tamura T., Ozato K.
    Mol. Cell. Biol. 33:2497-2507(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  28. Cited for: FUNCTION (ISOFORM B), SUBCELLULAR LOCATION (ISOFORM B), INTERACTION WITH NCAPD3 AND SMC2, MUTAGENESIS OF ASN-140.
  29. "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] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-37; GLY-371; ASN-563; SER-598 AND HIS-669.
  30. "Structural basis and binding properties of the second bromodomain of Brd4 with acetylated histone tails."
    Liu Y., Wang X., Zhang J., Huang H., Ding B., Wu J., Shi Y.
    Biochemistry 47:6403-6417(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 352-457.
  31. Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-168 IN COMPLEX WITH JQ1 INHIBITOR, SUBCELLULAR LOCATION.
  32. Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-168 IN COMPLEX WITH I-BET INHIBITOR.
  33. Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 44-168, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 333-460.
  34. Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 44-168 IN COMPLEX WITH JQ1 INHIBITOR.
  35. "Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family."
    Filippakopoulos P., Picaud S., Fedorov O., Keller M., Wrobel M., Morgenstern O., Bracher F., Knapp S.
    Bioorg. Med. Chem. 20:1878-1886(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-168 IN COMPLEX WITH BENZODIAZEPINES AND BENZOTRIAZEPINES INHIBITORS.
  36. "Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition."
    Zhang G., Liu R., Zhong Y., Plotnikov A.N., Zhang W., Zeng L., Rusinova E., Gerona-Nevarro G., Moshkina N., Joshua J., Chuang P.Y., Ohlmeyer M., He J.C., Zhou M.M.
    J. Biol. Chem. 287:28840-28851(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 44-168, STRUCTURE BY NMR OF 333-460.
  37. "Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery."
    Chung C.W., Dean A.W., Woolven J.M., Bamborough P.
    J. Med. Chem. 55:576-586(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 44-168 IN COMPLEX WITH BENZODIAZEPINES INHIBITORS.
  38. "Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit."
    Fish P.V., Filippakopoulos P., Bish G., Brennan P.E., Bunnage M.E., Cook A.S., Federov O., Gerstenberger B.S., Jones H., Knapp S., Marsden B., Nocka K., Owen D.R., Philpott M., Picaud S., Primiano M.J., Ralph M.J., Sciammetta N., Trzupek J.D.
    J. Med. Chem. 55:9831-9837(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 44-168.
  39. Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 44-168; 333-460 AND 1343-1362 IN COMPLEX WITH ACETYLATED HISTONE, MUTAGENESIS OF ASN-140 AND ASN-433.
  40. Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 44-168 IN COMPLEX WITH 3,5-DIMETHYLISOXAZOLE INHIBITOR.
  41. "Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain."
    Zhao L., Cao D., Chen T., Wang Y., Miao Z., Xu Y., Chen W., Wang X., Li Y., Du Z., Xiong B., Li J., Xu C., Zhang N., He J., Shen J.
    J. Med. Chem. 56:3833-3851(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 44-167 IN COMPLEX WITH 2-THIAZOLIDINONE INHIBITOR.

Entry informationi

Entry nameiBRD4_HUMAN
AccessioniPrimary (citable) accession number: O60885
Secondary accession number(s): O60433
, Q4G0X8, Q86YS8, Q96PD3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 31, 2002
Last modified: November 26, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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).3 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3