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Protein

Bromodomain-containing protein 4

Gene

BRD4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Binding sitei140Acetylated histones1 Publication1
Binding sitei140Inhibitor1
Binding sitei433Acetylated histones1 Publication1
Binding sitei433Inhibitor1

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • lysine-acetylated histone binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • RNA polymerase II core binding Source: MGI

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • chromatin modification Source: UniProtKB-KW
  • chromatin remodeling Source: UniProtKB
  • negative regulation of DNA damage checkpoint Source: UniProtKB
  • positive regulation of G2/M transition of mitotic cell cycle Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of transcription elongation from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of inflammatory response Source: UniProtKB
  • regulation of phosphorylation of RNA polymerase II C-terminal domain Source: UniProtKB
  • regulation of transcription involved in G1/S transition of mitotic cell cycle Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Biological processi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141867-MONOMER.
SIGNORiO60885.

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
Proteomesi
  • UP000005640 Componenti: 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

  • chromosome Source: UniProtKB
  • condensed nuclear chromosome Source: MGI
  • cytoplasm Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
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.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi140N → A: Abolishes binding to acetylated histones. 2 Publications1
Mutagenesisi433N → A: Abolishes binding to acetylated histones. 1 Publication1
Mutagenesisi492 – 494SSS → ASA: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication3
Mutagenesisi498 – 500SST → AAA: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication3
Mutagenesisi503S → A: Impaired phosphorylation by CK2 and binding to acetylated histones. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei719 – 720Breakpoint for translocation to form BDR4-NUT fusion protein2

Organism-specific databases

DisGeNETi23476.
OpenTargetsiENSG00000141867.
PharmGKBiPA25416.

Chemistry databases

ChEMBLiCHEMBL1163125.
GuidetoPHARMACOLOGYi1945.

Polymorphism and mutation databases

BioMutaiBRD4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002111831 – 1362Bromodomain-containing protein 4Add BLAST1362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei470PhosphoserineCombined sources1
Modified residuei484Phosphoserine; by CK21 Publication1
Modified residuei488Phosphoserine; by CK21 Publication1
Modified residuei492Phosphoserine; by CK21 Publication1
Modified residuei494Phosphoserine; by CK21 Publication1
Modified residuei498Phosphoserine; by CK21 Publication1
Modified residuei499Phosphoserine; by CK21 Publication1
Modified residuei503Phosphoserine; by CK21 Publication1
Modified residuei601PhosphoserineCombined sources1
Cross-linki694Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1111N6-acetyllysine; alternateCombined sources1
Cross-linki1111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki1111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1117PhosphoserineCombined sources1
Modified residuei1126PhosphoserineCombined sources1
Modified residuei1201PhosphoserineCombined sources1
Modified residuei1204PhosphoserineCombined sources1

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.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO60885.
MaxQBiO60885.
PaxDbiO60885.
PeptideAtlasiO60885.
PRIDEiO60885.

PTM databases

iPTMnetiO60885.
PhosphoSitePlusiO60885.

Miscellaneous databases

PMAP-CutDBO60885.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000141867.
CleanExiHS_BRD4.
ExpressionAtlasiO60885. baseline and differential.
GenevisibleiO60885. HS.

Organism-specific databases

HPAiCAB068177.
CAB068178.
HPA015055.
HPA061646.

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
HIST2H4BP628057EBI-9345088,EBI-302023
JMJD6Q6NYC110EBI-723869,EBI-8464037
NCK1P163332EBI-723869,EBI-389883
RELAQ042068EBI-723869,EBI-73886
TWIST1Q156729EBI-9345088,EBI-1797287

GO - Molecular functioni

  • lysine-acetylated histone binding Source: UniProtKB
  • p53 binding Source: UniProtKB
  • RNA polymerase II core binding Source: MGI

Protein-protein interaction databases

BioGridi117036. 72 interactors.
DIPiDIP-39776N.
IntActiO60885. 28 interactors.
MINTiMINT-1176376.
STRINGi9606.ENSP00000263377.

Chemistry databases

BindingDBiO60885.

Structurei

Secondary structure

11362
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi53 – 55Combined sources3
Helixi61 – 68Combined sources8
Helixi70 – 75Combined sources6
Helixi81 – 83Combined sources3
Turni89 – 93Combined sources5
Helixi97 – 100Combined sources4
Helixi107 – 115Combined sources9
Helixi122 – 139Combined sources18
Helixi145 – 161Combined sources17
Beta strandi342 – 346Combined sources5
Helixi350 – 364Combined sources15
Helixi367 – 369Combined sources3
Helixi370 – 373Combined sources4
Helixi374 – 376Combined sources3
Helixi382 – 385Combined sources4
Helixi390 – 393Combined sources4
Helixi400 – 408Combined sources9
Beta strandi412 – 414Combined sources3
Helixi415 – 432Combined sources18
Beta strandi435 – 437Combined sources3
Helixi438 – 454Combined sources17
Helixi602 – 605Combined sources4
Helixi612 – 624Combined sources13
Helixi627 – 640Combined sources14
Helixi642 – 644Combined sources3
Beta strandi651 – 655Combined sources5
Turni656 – 658Combined sources3
Helixi661 – 675Combined sources15
Helixi1345 – 1354Combined sources10
Turni1355 – 1357Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I8NNMR-A352-457[»]
2LSPNMR-B333-460[»]
2MJVNMR-B333-460[»]
2N3KNMR-A600-678[»]
2NCZNMR-A601-683[»]
2ND0NMR-A601-683[»]
2ND1NMR-A601-683[»]
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[»]
4CL9X-ray1.40A44-168[»]
4CLBX-ray1.60A44-168[»]
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[»]
4QB3X-ray0.94A44-168[»]
4QR3X-ray1.37A44-166[»]
4QR4X-ray1.28A44-166[»]
4QR5X-ray1.41A44-166[»]
4QZSX-ray1.45A44-168[»]
4UIXX-ray1.58A/B/C44-168[»]
4UIYX-ray1.30A44-168[»]
4UIZX-ray1.19A44-168[»]
4UYDX-ray1.37A44-183[»]
4WHWX-ray1.34A44-168[»]
4WIVX-ray1.56A44-168[»]
4X2IX-ray1.20A42-166[»]
4XY9X-ray1.83A42-168[»]
4XYAX-ray2.05A42-168[»]
4YH3X-ray1.60A44-170[»]
4YH4X-ray1.33A44-170[»]
4Z1QX-ray1.40A/B42-167[»]
4Z1SX-ray1.06A/B42-166[»]
4Z93X-ray1.27A349-460[»]
4ZC9X-ray0.99A44-168[»]
4ZW1X-ray1.75A44-168[»]
5A5SX-ray1.36A44-168[»]
5A85X-ray1.72A44-168[»]
5ACYX-ray2.01A/B44-168[»]
5AD2X-ray2.01A/B44-168[»]
5AD3X-ray1.49A/B44-168[»]
5BT4X-ray1.50A/B/C44-168[»]
5CFWX-ray1.15A44-168[»]
5COIX-ray1.62A44-168[»]
5CP5X-ray1.79A44-168[»]
5CPEX-ray1.62A44-168[»]
5CQTX-ray1.60A44-168[»]
5CRMX-ray1.99A44-168[»]
5CRZX-ray2.12A44-168[»]
5CS8X-ray1.62A44-168[»]
5CTLX-ray2.51A44-168[»]
5CY9X-ray1.55A44-168[»]
5D0CX-ray1.49A44-168[»]
5D24X-ray1.65A43-168[»]
5D25X-ray1.70A43-168[»]
5D26X-ray1.82A42-168[»]
5D3HX-ray1.70A44-168[»]
5D3JX-ray1.70A43-168[»]
5D3LX-ray1.50A42-168[»]
5D3NX-ray2.15A43-168[»]
5D3PX-ray1.95A42-168[»]
5D3RX-ray2.20A42-168[»]
5D3SX-ray1.75A44-168[»]
5D3TX-ray1.93A42-168[»]
5DLXX-ray1.90A44-168[»]
5DLZX-ray1.70A44-168[»]
5DW2X-ray1.12A44-170[»]
5DX4X-ray2.30A44-168[»]
5E0RX-ray1.35A44-168[»]
5EGUX-ray2.21A/B/C/D44-168[»]
5EI4X-ray1.05A44-168[»]
5EISX-ray1.60A44-168[»]
5FBXX-ray1.85A44-168[»]
5HLSX-ray2.18A42-168[»]
5HM0X-ray1.40A42-168[»]
5I80X-ray1.45A42-167[»]
5I88X-ray1.40A42-167[»]
5IGKX-ray1.70A44-168[»]
5JWMX-ray1.71A/B333-460[»]
5KHMX-ray1.48A/B44-168[»]
5LJ1X-ray1.90A42-168[»]
5LJ2X-ray1.19A42-168[»]
5LUUX-ray1.61A44-168[»]
ProteinModelPortaliO60885.
SMRiO60885.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60885.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 147Bromo 1PROSITE-ProRule annotationAdd BLAST73
Domaini368 – 440Bromo 2PROSITE-ProRule annotationAdd BLAST73
Domaini600 – 682NETPROSITE-ProRule annotationAdd BLAST83

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni484 – 503NPS regionAdd BLAST20
Regioni524 – 579BID regionAdd BLAST56
Regioni1047 – 1362C-terminal (CTD) regionAdd BLAST316

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi535 – 594Lys-richAdd BLAST60
Compositional biasi692 – 717Ser-richAdd BLAST26
Compositional biasi703 – 714Poly-SerAdd BLAST12
Compositional biasi738 – 743Poly-His6
Compositional biasi757 – 761Poly-Pro5
Compositional biasi764 – 770Poly-Pro7
Compositional biasi771 – 775Poly-Gln5
Compositional biasi776 – 783Poly-Pro8
Compositional biasi954 – 964Poly-ProAdd BLAST11
Compositional biasi974 – 986Poly-ProAdd BLAST13
Compositional biasi1011 – 1014Poly-Pro4
Compositional biasi1028 – 1033Poly-Pro6
Compositional biasi1283 – 1300Poly-GlnAdd BLAST18
Compositional biasi1301 – 1308Poly-Ala8
Compositional biasi1335 – 1338Poly-Arg4

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

eggNOGiKOG1474. Eukaryota.
COG5076. LUCA.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiO60885.
KOiK11722.
OMAiQPQSMLD.
OrthoDBiEOG091G01QC.
PhylomeDBiO60885.
TreeFamiTF317345.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR031354. BRD4_CDT.
IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF17035. BET. 1 hit.
PF17105. BRD4_CDT. 1 hit.
PF00439. 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. AlignAdd to basket

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 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04191937P → S.1 PublicationCorresponds to variant rs35177876dbSNPEnsembl.1
Natural variantiVAR_041920371A → G.1 PublicationCorresponds to variant rs55805532dbSNPEnsembl.1
Natural variantiVAR_041921563S → N.1 PublicationCorresponds to variant rs55970906dbSNPEnsembl.1
Natural variantiVAR_041922598T → S.1 PublicationCorresponds to variant rs34362023dbSNPEnsembl.1
Natural variantiVAR_041923669R → H.1 PublicationCorresponds to variant rs35824241dbSNPEnsembl.1
Natural variantiVAR_0484271097R → H.Corresponds to variant rs35676845dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047671720 – 1362EMAPK…EENLF → AFCTSGDFVSPGPSPYHSHV QCGRFREMLRWFLVDVEQTA AGQPHRQSAAGPAITWAPAI AYPSPECARCCVGCS in isoform B. 1 PublicationAdd BLAST643
Alternative sequenceiVSP_010902720 – 722EMA → GPA in isoform C. 1 Publication3
Alternative sequenceiVSP_010903723 – 1362Missing in isoform C. 1 PublicationAdd BLAST640

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]
CCDS82307.1. [O60885-3]
RefSeqiNP_001317313.1. NM_001330384.1.
NP_055114.1. NM_014299.2. [O60885-2]
NP_490597.1. NM_058243.2. [O60885-1]
XP_011526156.1. XM_011527854.1. [O60885-1]
XP_011526158.1. XM_011527856.2. [O60885-2]
UniGeneiHs.187763.

Genome annotation databases

EnsembliENST00000263377; ENSP00000263377; ENSG00000141867. [O60885-1]
ENST00000360016; ENSP00000353112; ENSG00000141867. [O60885-3]
ENST00000371835; ENSP00000360901; ENSG00000141867. [O60885-2]
GeneIDi23476.
KEGGihsa:23476.
UCSCiuc002nar.4. human. [O60885-1]

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.
CCDSiCCDS12328.1. [O60885-1]
CCDS46004.1. [O60885-2]
CCDS82307.1. [O60885-3]
RefSeqiNP_001317313.1. NM_001330384.1.
NP_055114.1. NM_014299.2. [O60885-2]
NP_490597.1. NM_058243.2. [O60885-1]
XP_011526156.1. XM_011527854.1. [O60885-1]
XP_011526158.1. XM_011527856.2. [O60885-2]
UniGeneiHs.187763.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I8NNMR-A352-457[»]
2LSPNMR-B333-460[»]
2MJVNMR-B333-460[»]
2N3KNMR-A600-678[»]
2NCZNMR-A601-683[»]
2ND0NMR-A601-683[»]
2ND1NMR-A601-683[»]
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[»]
4CL9X-ray1.40A44-168[»]
4CLBX-ray1.60A44-168[»]
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[»]
4QB3X-ray0.94A44-168[»]
4QR3X-ray1.37A44-166[»]
4QR4X-ray1.28A44-166[»]
4QR5X-ray1.41A44-166[»]
4QZSX-ray1.45A44-168[»]
4UIXX-ray1.58A/B/C44-168[»]
4UIYX-ray1.30A44-168[»]
4UIZX-ray1.19A44-168[»]
4UYDX-ray1.37A44-183[»]
4WHWX-ray1.34A44-168[»]
4WIVX-ray1.56A44-168[»]
4X2IX-ray1.20A42-166[»]
4XY9X-ray1.83A42-168[»]
4XYAX-ray2.05A42-168[»]
4YH3X-ray1.60A44-170[»]
4YH4X-ray1.33A44-170[»]
4Z1QX-ray1.40A/B42-167[»]
4Z1SX-ray1.06A/B42-166[»]
4Z93X-ray1.27A349-460[»]
4ZC9X-ray0.99A44-168[»]
4ZW1X-ray1.75A44-168[»]
5A5SX-ray1.36A44-168[»]
5A85X-ray1.72A44-168[»]
5ACYX-ray2.01A/B44-168[»]
5AD2X-ray2.01A/B44-168[»]
5AD3X-ray1.49A/B44-168[»]
5BT4X-ray1.50A/B/C44-168[»]
5CFWX-ray1.15A44-168[»]
5COIX-ray1.62A44-168[»]
5CP5X-ray1.79A44-168[»]
5CPEX-ray1.62A44-168[»]
5CQTX-ray1.60A44-168[»]
5CRMX-ray1.99A44-168[»]
5CRZX-ray2.12A44-168[»]
5CS8X-ray1.62A44-168[»]
5CTLX-ray2.51A44-168[»]
5CY9X-ray1.55A44-168[»]
5D0CX-ray1.49A44-168[»]
5D24X-ray1.65A43-168[»]
5D25X-ray1.70A43-168[»]
5D26X-ray1.82A42-168[»]
5D3HX-ray1.70A44-168[»]
5D3JX-ray1.70A43-168[»]
5D3LX-ray1.50A42-168[»]
5D3NX-ray2.15A43-168[»]
5D3PX-ray1.95A42-168[»]
5D3RX-ray2.20A42-168[»]
5D3SX-ray1.75A44-168[»]
5D3TX-ray1.93A42-168[»]
5DLXX-ray1.90A44-168[»]
5DLZX-ray1.70A44-168[»]
5DW2X-ray1.12A44-170[»]
5DX4X-ray2.30A44-168[»]
5E0RX-ray1.35A44-168[»]
5EGUX-ray2.21A/B/C/D44-168[»]
5EI4X-ray1.05A44-168[»]
5EISX-ray1.60A44-168[»]
5FBXX-ray1.85A44-168[»]
5HLSX-ray2.18A42-168[»]
5HM0X-ray1.40A42-168[»]
5I80X-ray1.45A42-167[»]
5I88X-ray1.40A42-167[»]
5IGKX-ray1.70A44-168[»]
5JWMX-ray1.71A/B333-460[»]
5KHMX-ray1.48A/B44-168[»]
5LJ1X-ray1.90A42-168[»]
5LJ2X-ray1.19A42-168[»]
5LUUX-ray1.61A44-168[»]
ProteinModelPortaliO60885.
SMRiO60885.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117036. 72 interactors.
DIPiDIP-39776N.
IntActiO60885. 28 interactors.
MINTiMINT-1176376.
STRINGi9606.ENSP00000263377.

Chemistry databases

BindingDBiO60885.
ChEMBLiCHEMBL1163125.
GuidetoPHARMACOLOGYi1945.

PTM databases

iPTMnetiO60885.
PhosphoSitePlusiO60885.

Polymorphism and mutation databases

BioMutaiBRD4.

Proteomic databases

EPDiO60885.
MaxQBiO60885.
PaxDbiO60885.
PeptideAtlasiO60885.
PRIDEiO60885.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263377; ENSP00000263377; ENSG00000141867. [O60885-1]
ENST00000360016; ENSP00000353112; ENSG00000141867. [O60885-3]
ENST00000371835; ENSP00000360901; ENSG00000141867. [O60885-2]
GeneIDi23476.
KEGGihsa:23476.
UCSCiuc002nar.4. human. [O60885-1]

Organism-specific databases

CTDi23476.
DisGeNETi23476.
GeneCardsiBRD4.
HGNCiHGNC:13575. BRD4.
HPAiCAB068177.
CAB068178.
HPA015055.
HPA061646.
MIMi608749. gene.
neXtProtiNX_O60885.
OpenTargetsiENSG00000141867.
PharmGKBiPA25416.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1474. Eukaryota.
COG5076. LUCA.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiO60885.
KOiK11722.
OMAiQPQSMLD.
OrthoDBiEOG091G01QC.
PhylomeDBiO60885.
TreeFamiTF317345.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141867-MONOMER.
SIGNORiO60885.

Miscellaneous databases

ChiTaRSiBRD4. human.
EvolutionaryTraceiO60885.
GeneWikiiBRD4.
GenomeRNAii23476.
PMAP-CutDBO60885.
PROiO60885.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141867.
CleanExiHS_BRD4.
ExpressionAtlasiO60885. baseline and differential.
GenevisibleiO60885. HS.

Family and domain databases

Gene3Di1.20.920.10. 2 hits.
InterProiIPR031354. BRD4_CDT.
IPR001487. Bromodomain.
IPR018359. Bromodomain_CS.
IPR027353. NET_dom.
[Graphical view]
PfamiPF17035. BET. 1 hit.
PF17105. BRD4_CDT. 1 hit.
PF00439. 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]
ProtoNetiSearch...

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 30, 2016
This is version 157 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.