Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(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)

O60885

- BRD4_HUMAN

UniProt

O60885 - BRD4_HUMAN

Protein

Bromodomain-containing protein 4

Gene

BRD4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (31 Jan 2002)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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
    5. protein 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

    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

    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.
    Mutagenesisi498 – 5003SST → AAA: Impaired phosphorylation by CK2 and binding to acetylated histones.
    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

    ArrayExpressiO60885.
    BgeeiO60885.
    CleanExiHS_BRD4.
    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. 40 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 – 553
    Helixi61 – 688
    Helixi70 – 756
    Helixi81 – 833
    Helixi89 – 924
    Helixi97 – 1004
    Helixi107 – 1159
    Helixi122 – 13918
    Helixi145 – 16117
    Beta strandi342 – 3465
    Helixi350 – 36415
    Helixi367 – 3693
    Helixi370 – 3734
    Helixi374 – 3763
    Helixi382 – 3854
    Helixi390 – 3934
    Helixi400 – 4089
    Beta strandi412 – 4143
    Helixi415 – 43218
    Beta strandi435 – 4373
    Helixi438 – 45518

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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[»]
    ProteinModelPortaliO60885.
    SMRiO60885. Positions 44-225, 333-460, 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.
    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

    MSAESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET     50
    SNPNKPKRQT NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI 100
    IKTPMDMGTI KKRLENNYYW NAQECIQDFN TMFTNCYIYN KPGDDIVLMA 150
    EALEKLFLQK INELPTEETE IMIVQAKGRG RGRKETGTAK PGVSTVPNTT 200
    QASTPPQTQT PQPNPPPVQA TPHPFPAVTP DLIVQTPVMT VVPPQPLQTP 250
    PPVPPQPQPP PAPAPQPVQS HPPIIAATPQ PVKTKKGVKR KADTTTPTTI 300
    DPIHEPPSLP PEPKTTKLGQ RRESSRPVKP PKKDVPDSQQ HPAPEKSSKV 350
    SEQLKCCSGI LKEMFAKKHA AYAWPFYKPV DVEALGLHDY CDIIKHPMDM 400
    STIKSKLEAR EYRDAQEFGA DVRLMFSNCY KYNPPDHEVV AMARKLQDVF 450
    EMRFAKMPDE PEEPVVAVSS PAVPPPTKVV APPSSSDSSS DSSSDSDSST 500
    DDSEEERAQR LAELQEQLKA VHEQLAALSQ PQQNKPKKKE KDKKEKKKEK 550
    HKRKEEVEEN KKSKAKEPPP KKTKKNNSSN SNVSKKEPAP MKSKPPPTYE 600
    SEEEDKCKPM SYEEKRQLSL DINKLPGEKL GRVVHIIQSR EPSLKNSNPD 650
    EIEIDFETLK PSTLRELERY VTSCLRKKRK PQAEKVDVIA GSSKMKGFSS 700
    SESESSSESS SSDSEDSETE MAPKSKKKGH PGREQKKHHH HHHQQMQQAP 750
    APVPQQPPPP PQQPPPPPPP QQQQQPPPPP PPPSMPQQAA PAMKSSPPPF 800
    IATQVPVLEP QLPGSVFDPI GHFTQPILHL PQPELPPHLP QPPEHSTPPH 850
    LNQHAVVSPP ALHNALPQQP SRPSNRAAAL PPKPARPPAV SPALTQTPLL 900
    PQPPMAQPPQ VLLEDEEPPA PPLTSMQMQL YLQQLQKVQP PTPLLPSVKV 950
    QSQPPPPLPP PPHPSVQQQL QQQPPPPPPP QPQPPPQQQH QPPPRPVHLQ 1000
    PMQFSTHIQQ PPPPQGQQPP HPPPGQQPPP PQPAKPQQVI QHHHSPRHHK 1050
    SDPYSTGHLR EAPSPLMIHS PQMSQFQSLT HQSPPQQNVQ PKKQELRAAS 1100
    VVQPQPLVVV KEEKIHSPII RSEPFSPSLR PEPPKHPESI KAPVHLPQRP 1150
    EMKPVDVGRP VIRPPEQNAP PPGAPDKDKQ KQEPKTPVAP KKDLKIKNMG 1200
    SWASLVQKHP TTPSSTAKSS SDSFEQFRRA AREKEEREKA LKAQAEHAEK 1250
    EKERLRQERM RSREDEDALE QARRAHEEAR RRQEQQQQQR QEQQQQQQQQ 1300
    AAAVAAAATP QAQSSQPQSM LDQQRELARK REQERRRREA MAATIDMNFQ 1350
    SDLLSIFEEN LF 1362
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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 [» ]
    ProteinModelPortali O60885.
    SMRi O60885. Positions 44-225, 333-460, 605-682.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117036. 40 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.
    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

    ArrayExpressi O60885.
    Bgeei O60885.
    CleanExi HS_BRD4.
    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

    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: October 1, 2014
    This is version 133 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