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Protein

Bromodomain-containing protein 4

Gene

Brd4

Organism
Mus musculus (Mouse)
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. 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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei140 – 1401Acetylated histones1 Publication
Binding sitei140 – 1401InhibitorBy similarity
Binding sitei434 – 4341Acetylated histonesBy similarity
Binding sitei434 – 4341InhibitorBy similarity

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • lysine-acetylated histone binding Source: UniProtKB
  • p53 binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Biological processi

Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Bromodomain-containing protein 4
Alternative name(s):
Mitotic chromosome-associated protein
Short name:
MCAP
Gene namesi
Name:Brd4
Synonyms:Mcap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1888520. 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. Preferentially localizes to mitotic chromosomes, while it does not localizes to meiotic chromosomes.

GO - Cellular componenti

  • condensed nuclear chromosome Source: MGI
  • nuclear chromatin Source: MGI
  • nucleus Source: MGI
  • positive transcription elongation factor complex b Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic lethal. Embryos ndie shortly after implantation and are compromised in their ability to maintain an inner cell mass.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi139 – 1391Y → A: No effect on acetylated histone binding. 1 Publication
Mutagenesisi146 – 1461I → A: No effect on acetylated histone binding. 1 Publication
Mutagenesisi433 – 4331Y → A: No effect on acetylated histone binding. 1 Publication
Mutagenesisi440 – 4401V → A: No effect on acetylated histone binding. 1 Publication

Chemistry

ChEMBLiCHEMBL3085619.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14001400Bromodomain-containing protein 4PRO_0000211184Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei471 – 4711PhosphoserineBy similarity
Modified residuei485 – 4851Phosphoserine; by CK2By similarity
Modified residuei489 – 4891Phosphoserine; by CK2By similarity
Modified residuei493 – 4931Phosphoserine; by CK2By similarity
Modified residuei495 – 4951PhosphoserineBy similarity
Modified residuei499 – 4991Phosphoserine; by CK2By similarity
Modified residuei500 – 5001Phosphoserine; by CK2By similarity
Modified residuei504 – 5041Phosphoserine; by CK2By similarity
Modified residuei602 – 6021PhosphoserineBy similarity
Cross-linki695 – 695Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1147 – 11471N6-acetyllysine; alternateBy similarity
Cross-linki1147 – 1147Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei1153 – 11531PhosphoserineBy similarity

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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9ESU6.
MaxQBiQ9ESU6.
PaxDbiQ9ESU6.
PRIDEiQ9ESU6.

PTM databases

iPTMnetiQ9ESU6.
PhosphoSiteiQ9ESU6.

Expressioni

Gene expression databases

BgeeiQ9ESU6.
CleanExiMM_BRD4.
ExpressionAtlasiQ9ESU6. baseline and differential.
GenevisibleiQ9ESU6. MM.

Interactioni

Subunit structurei

Interacts with p53/TP53; the interaction is direct. Interacts with RELA (when acetylated at 'Lys-310'). Interacts (via NET domain) with WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5 (By similarity). Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RELAQ042066EBI-6260864,EBI-73886From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208231. 1 interaction.
IntActiQ9ESU6. 5 interactions.
MINTiMINT-1176459.
STRINGi10090.ENSMUSP00000113070.

Chemistry

BindingDBiQ9ESU6.

Structurei

Secondary structure

1
1400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi61 – 688Combined sources
Helixi70 – 745Combined sources
Helixi81 – 833Combined sources
Helixi89 – 924Combined sources
Helixi97 – 1004Combined sources
Helixi107 – 11610Combined sources
Helixi122 – 13918Combined sources
Helixi145 – 16016Combined sources
Helixi353 – 36513Combined sources
Helixi368 – 3703Combined sources
Helixi371 – 3744Combined sources
Helixi375 – 3773Combined sources
Helixi383 – 3864Combined sources
Helixi391 – 3944Combined sources
Helixi401 – 4099Combined sources
Helixi416 – 43318Combined sources
Helixi439 – 45517Combined sources
Turni602 – 6054Combined sources
Helixi613 – 62311Combined sources
Helixi628 – 6314Combined sources
Helixi634 – 6396Combined sources
Helixi643 – 6453Combined sources
Turni657 – 6593Combined sources
Helixi662 – 67312Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWWX-ray1.80A347-460[»]
2JNSNMR-A601-683[»]
3JVJX-ray1.55A42-168[»]
3JVKX-ray1.80A42-168[»]
3JVLX-ray1.20A349-464[»]
3JVMX-ray1.20A349-464[»]
3MUKX-ray1.75A42-168[»]
3MULX-ray1.65A42-168[»]
ProteinModelPortaliQ9ESU6.
SMRiQ9ESU6. Positions 44-166, 349-460, 606-683.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9ESU6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 14773Bromo 1PROSITE-ProRule annotationAdd
BLAST
Domaini369 – 44173Bromo 2PROSITE-ProRule annotationAdd
BLAST
Domaini601 – 68383NETPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni485 – 50420NPS regionBy similarityAdd
BLAST
Regioni525 – 58056BID regionBy similarityAdd
BLAST
Regioni1050 – 1400351C-terminal (CTD) regionBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi206 – 345140Pro-richAdd
BLAST
Compositional biasi485 – 50420Ser-richAdd
BLAST
Compositional biasi536 – 59560Lys-richAdd
BLAST
Compositional biasi693 – 71826Ser-richAdd
BLAST
Compositional biasi745 – 1226482Pro-richAdd
BLAST
Compositional biasi929 – 1115187Gln-richAdd
BLAST
Compositional biasi1319 – 136244Gln-richAdd
BLAST

Domaini

The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-434, respectively (PubMed:19828451). 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 (By similarity).By similarity1 Publication
The NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (WHSC1L1, JMJD6, CHD4, GLTSCR1 and ATAD5).By similarity
The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex. It is also required for maintenance of higher-order chromatin structure (By similarity).By similarity

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.
InParanoidiQ9ESU6.
KOiK11722.
OrthoDBiEOG7TTQ86.
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9ESU6-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSTESGPGTR 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 RGRKETGAAK PGVSTVPNTT
210 220 230 240 250
QASTSPQTQT PQQNPPPPVQ ATTHPFPAVT PDLIAQPPVM TMVPPQPLQT
260 270 280 290 300
PSPVPPQPPP PPAPVPQPVQ SHPPIIATTP QPVKTKKGVK RKADTTTPTT
310 320 330 340 350
IDPIHEPPSL APEPKTAKLG PRRESSRPVK PPKKDVPDSQ QHPGPEKSSK
360 370 380 390 400
ISEQLKCCSG ILKEMFAKKH AAYAWPFYKP VDVEALGLHD YCDIIKHPMD
410 420 430 440 450
MSTIKSKLES REYRDAQEFG ADVRLMFSNC YKYNPPDHEV VAMARKLQDV
460 470 480 490 500
FEMRFAKMPD EPEEPVVTVS SPAVPPPTKV VAPPSSSDSS SDSSSDSDSS
510 520 530 540 550
TDDSEEERAQ RLAELQEQLK AVHEQLAALS QPQQNKPKKK EKDKKEKKKE
560 570 580 590 600
KHKKKEEVEE NKKSKTKELP PKKTKKNNSS NSNVSKKEPV PTKTKPPPTY
610 620 630 640 650
ESEEEDKCKP MSYEEKRQLS LDINKLPGEK LGRVVHIIQS REPSLKNSNP
660 670 680 690 700
DEIEIDFETL KPSTLRELER YVTSCLRKKR KPQAEKVDVI AGSSKMKGFS
710 720 730 740 750
SSESESTSES SSSDSEDSET EMAPKSKKKG HTGRDQKKHH HHHHPQMQPA
760 770 780 790 800
PAPVPQQPPP PPQQPPPPPP PQQQQQQPPP PPPPPSMPQQ TAPAMKSSPP
810 820 830 840 850
PFITAQVPVL EPQLPGSVFD PIGHFTQPIL HLPQPELPPH LPQPPEHSTP
860 870 880 890 900
PHLNQHAVVS PPALHNALPQ QPSRPSNRAA ALPPKPTRPP AVSPALAQPP
910 920 930 940 950
LLPQPPMAQP PQVLLEDEEP PAPPLTSMQM QLYLQQLQKV QPPTPLLPSV
960 970 980 990 1000
KVQSQPPPPL PPPPHPSVQQ QQLQPQPPPP PPPQPQPPPQ QQHQPPPRPV
1010 1020 1030 1040 1050
HLPSMPFSAH IQQPPPPPGQ QPTHPPPGQQ PPPPQPAKPQ QVIQHHPSPR
1060 1070 1080 1090 1100
HHKSDPYSAG HLREAPSPLM IHSPQMPQFQ SLTHQSPPQQ NVQPKKQVKG
1110 1120 1130 1140 1150
RAEPQPPGPV MGQGQGCPPA SPAAVPMLSQ ELRPPSVVQP QPLVVVKEEK
1160 1170 1180 1190 1200
IHSPIIRSEP FSTSLRPEPP KHPENIKAPV HLPQRPEMKP VDIGRPVIRP
1210 1220 1230 1240 1250
PEQSAPPPGA PDKDKQKQEP KTPVAPKKDL KIKNMGSWAS LVQKHPTTPS
1260 1270 1280 1290 1300
STAKSSSDSF EHFRRAAREK EEREKALKAQ AEHAEKEKER LRQERMRSRE
1310 1320 1330 1340 1350
DEDALEQARR AHEEARRRQE QQQQQQQQRQ EQQQQQQQAA AVAAASAPQA
1360 1370 1380 1390 1400
QSSQPQSMLD QQRELARKRE QERRRREAMA ATIDMNFQSD LLSIFEENLF
Length:1,400
Mass (Da):155,895
Last modified:July 24, 2013 - v2
Checksum:i3D90F6D3254D5691
GO
Isoform 2 (identifier: Q9ESU6-2) [UniParc]FASTAAdd to basket

Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     721-723: EMA → GPA
     724-1400: Missing.

Show »
Length:723
Mass (Da):80,605
Checksum:iF1115540F58A56B8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti188 – 1881A → T in AAL67834 (PubMed:11997514).Curated
Sequence conflicti823 – 8231G → S in AAL67833 (PubMed:11997514).Curated
Sequence conflicti908 – 9081A → V in AAG02191 (PubMed:10938129).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei721 – 7233EMA → GPA in isoform 2. 1 PublicationVSP_010904
Alternative sequencei724 – 1400677Missing in isoform 2. 1 PublicationVSP_010905Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF273217 mRNA. Translation: AAG02191.1.
AF461395 mRNA. Translation: AAL67833.1.
AF461396 mRNA. Translation: AAL67834.1.
CT033751 Genomic DNA. No translation available.
CT033755 Genomic DNA. No translation available.
CH466640 Genomic DNA. Translation: EDL40326.1.
CH466640 Genomic DNA. Translation: EDL40329.1.
CCDSiCCDS37554.1. [Q9ESU6-2]
CCDS50057.1. [Q9ESU6-1]
RefSeqiNP_065254.3. NM_020508.4. [Q9ESU6-1]
NP_932762.2. NM_198094.2. [Q9ESU6-2]
XP_006524751.1. XM_006524688.1. [Q9ESU6-1]
XP_006524752.1. XM_006524689.2. [Q9ESU6-1]
UniGeneiMm.253518.

Genome annotation databases

EnsembliENSMUST00000114475; ENSMUSP00000110119; ENSMUSG00000024002. [Q9ESU6-2]
ENSMUST00000119123; ENSMUSP00000113197; ENSMUSG00000024002. [Q9ESU6-1]
ENSMUST00000121285; ENSMUSP00000113070; ENSMUSG00000024002. [Q9ESU6-1]
GeneIDi57261.
KEGGimmu:57261.
UCSCiuc008bwa.3. mouse. [Q9ESU6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF273217 mRNA. Translation: AAG02191.1.
AF461395 mRNA. Translation: AAL67833.1.
AF461396 mRNA. Translation: AAL67834.1.
CT033751 Genomic DNA. No translation available.
CT033755 Genomic DNA. No translation available.
CH466640 Genomic DNA. Translation: EDL40326.1.
CH466640 Genomic DNA. Translation: EDL40329.1.
CCDSiCCDS37554.1. [Q9ESU6-2]
CCDS50057.1. [Q9ESU6-1]
RefSeqiNP_065254.3. NM_020508.4. [Q9ESU6-1]
NP_932762.2. NM_198094.2. [Q9ESU6-2]
XP_006524751.1. XM_006524688.1. [Q9ESU6-1]
XP_006524752.1. XM_006524689.2. [Q9ESU6-1]
UniGeneiMm.253518.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DWWX-ray1.80A347-460[»]
2JNSNMR-A601-683[»]
3JVJX-ray1.55A42-168[»]
3JVKX-ray1.80A42-168[»]
3JVLX-ray1.20A349-464[»]
3JVMX-ray1.20A349-464[»]
3MUKX-ray1.75A42-168[»]
3MULX-ray1.65A42-168[»]
ProteinModelPortaliQ9ESU6.
SMRiQ9ESU6. Positions 44-166, 349-460, 606-683.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208231. 1 interaction.
IntActiQ9ESU6. 5 interactions.
MINTiMINT-1176459.
STRINGi10090.ENSMUSP00000113070.

Chemistry

BindingDBiQ9ESU6.
ChEMBLiCHEMBL3085619.

PTM databases

iPTMnetiQ9ESU6.
PhosphoSiteiQ9ESU6.

Proteomic databases

EPDiQ9ESU6.
MaxQBiQ9ESU6.
PaxDbiQ9ESU6.
PRIDEiQ9ESU6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000114475; ENSMUSP00000110119; ENSMUSG00000024002. [Q9ESU6-2]
ENSMUST00000119123; ENSMUSP00000113197; ENSMUSG00000024002. [Q9ESU6-1]
ENSMUST00000121285; ENSMUSP00000113070; ENSMUSG00000024002. [Q9ESU6-1]
GeneIDi57261.
KEGGimmu:57261.
UCSCiuc008bwa.3. mouse. [Q9ESU6-1]

Organism-specific databases

CTDi23476.
MGIiMGI:1888520. Brd4.

Phylogenomic databases

eggNOGiKOG1474. Eukaryota.
COG5076. LUCA.
GeneTreeiENSGT00760000119206.
HOGENOMiHOG000231200.
HOVERGENiHBG004896.
InParanoidiQ9ESU6.
KOiK11722.
OrthoDBiEOG7TTQ86.
TreeFamiTF317345.

Miscellaneous databases

ChiTaRSiBrd4. mouse.
EvolutionaryTraceiQ9ESU6.
NextBioi313577.
PROiQ9ESU6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9ESU6.
CleanExiMM_BRD4.
ExpressionAtlasiQ9ESU6. baseline and differential.
GenevisibleiQ9ESU6. MM.

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...

Publicationsi

« Hide 'large scale' publications
  1. "A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition."
    Dey A., Ellenberg J., Farina A., Coleman A.E., Maruyama T., Sciortino S., Lippincott-Schwartz J., Ozato K.
    Mol. Cell. Biol. 20:6537-6549(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, FUNCTION.
  2. "Growth and early postimplantation defects in mice deficient for the bromodomain-containing protein Brd4."
    Houzelstein D., Bullock S.L., Lynch D.E., Grigorieva E.F., Wilson V.A., Beddington R.S.P.
    Mol. Cell. Biol. 22:3794-3802(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), DISRUPTION PHENOTYPE.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis."
    Dey A., Chitsaz F., Abbasi A., Misteli T., Ozato K.
    Proc. Natl. Acad. Sci. U.S.A. 100:8758-8763(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-139; ILE-146; TYR-433 AND VAL-440.
  6. "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.
  7. "Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis."
    Nagashima T., Maruyama T., Furuya M., Kajitani T., Uchida H., Masuda H., Ono M., Arase T., Ozato K., Yoshimura Y.
    Mol. Hum. Reprod. 13:141-148(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. Cited for: POSSIBLE ROLE OF I-BET INHIBITOR IN TUMOR.
  9. Cited for: POSSIBLE ROLE OF JQ1 INHIBITOR IN TUMOR.
  10. "Activation of JNK triggers release of Brd4 from mitotic chromosomes and mediates protection from drug-induced mitotic stress."
    Nishiyama A., Dey A., Tamura T., Ko M., Ozato K.
    PLoS ONE 7:E34719-E34719(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  11. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast.
  12. "Crystal structure of bromodomain-containing protein 4."
    RIKEN structural genomics initiative (RSGI)
    Submitted (AUG-2007) to the PDB data bank
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 347-460, STRUCTURE BY NMR OF 601-683.
  13. "Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution."
    Vollmuth F., Blankenfeldt W., Geyer M.
    J. Biol. Chem. 284:36547-36556(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 42-168 IN COMPLEX WITH ACETYLATED HISTONE, X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 349-464.
  14. "Interaction of propionylated and butyrylated histone H3 lysine marks with Brd4 bromodomains."
    Vollmuth F., Geyer M.
    Angew. Chem. Int. Ed. 49:6768-6772(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 42-168.

Entry informationi

Entry nameiBRD4_MOUSE
AccessioniPrimary (citable) accession number: Q9ESU6
Secondary accession number(s): B0V2V7, Q8VHF7, Q8VHF8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 24, 2013
Last modified: May 11, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Some specific inhibitors of Brd4 that prevent binding to acetylated histones by binding Asn-140 and Asn-434 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. 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:21814200, PubMed:21964340).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.