BRD4_MOUSE
ID BRD4_MOUSE Reviewed; 1400 AA.
AC Q9ESU6; B0V2V7; Q8VHF7; Q8VHF8;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2013, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Bromodomain-containing protein 4;
DE AltName: Full=Mitotic chromosome-associated protein;
DE Short=MCAP;
GN Name=Brd4; Synonyms=Mcap;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=10938129; DOI=10.1128/mcb.20.17.6537-6549.2000;
RA Dey A., Ellenberg J., Farina A., Coleman A.E., Maruyama T., Sciortino S.,
RA Lippincott-Schwartz J., Ozato K.;
RT "A bromodomain protein, MCAP, associates with mitotic chromosomes and
RT affects G(2)-to-M transition.";
RL Mol. Cell. Biol. 20:6537-6549(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND DISRUPTION PHENOTYPE.
RX PubMed=11997514; DOI=10.1128/mcb.22.11.3794-3802.2002;
RA Houzelstein D., Bullock S.L., Lynch D.E., Grigorieva E.F., Wilson V.A.,
RA Beddington R.S.P.;
RT "Growth and early postimplantation defects in mice deficient for the
RT bromodomain-containing protein Brd4.";
RL Mol. Cell. Biol. 22:3794-3802(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-139; ILE-146; TYR-433 AND
RP VAL-440.
RX PubMed=12840145; DOI=10.1073/pnas.1433065100;
RA Dey A., Chitsaz F., Abbasi A., Misteli T., Ozato K.;
RT "The double bromodomain protein Brd4 binds to acetylated chromatin during
RT interphase and mitosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8758-8763(2003).
RN [6]
RP FUNCTION, AND INTERACTION WITH CDK9 AND CCNT1.
RX PubMed=16109376; DOI=10.1016/j.molcel.2005.06.027;
RA Jang M.K., Mochizuki K., Zhou M., Jeong H.S., Brady J.N., Ozato K.;
RT "The bromodomain protein Brd4 is a positive regulatory component of P-TEFb
RT and stimulates RNA polymerase II-dependent transcription.";
RL Mol. Cell 19:523-534(2005).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17267518; DOI=10.1093/molehr/gal115;
RA Nagashima T., Maruyama T., Furuya M., Kajitani T., Uchida H., Masuda H.,
RA Ono M., Arase T., Ozato K., Yoshimura Y.;
RT "Histone acetylation and subcellular localization of chromosomal protein
RT BRD4 during mouse oocyte meiosis and mitosis.";
RL Mol. Hum. Reprod. 13:141-148(2007).
RN [8]
RP POSSIBLE ROLE OF I-BET INHIBITOR IN TUMOR.
RX PubMed=21814200; DOI=10.1038/nature10334;
RA Zuber J., Shi J., Wang E., Rappaport A.R., Herrmann H., Sison E.A.,
RA Magoon D., Qi J., Blatt K., Wunderlich M., Taylor M.J., Johns C.,
RA Chicas A., Mulloy J.C., Kogan S.C., Brown P., Valent P., Bradner J.E.,
RA Lowe S.W., Vakoc C.R.;
RT "RNAi screen identifies Brd4 as a therapeutic target in acute myeloid
RT leukaemia.";
RL Nature 478:524-528(2011).
RN [9]
RP POSSIBLE ROLE OF JQ1 INHIBITOR IN TUMOR.
RX PubMed=21964340; DOI=10.1038/nature10509;
RA Dawson M.A., Prinjha R.K., Dittmann A., Giotopoulos G., Bantscheff M.,
RA Chan W.I., Robson S.C., Chung C.W., Hopf C., Savitski M.M., Huthmacher C.,
RA Gudgin E., Lugo D., Beinke S., Chapman T.D., Roberts E.J., Soden P.E.,
RA Auger K.R., Mirguet O., Doehner K., Delwel R., Burnett A.K., Jeffrey P.,
RA Drewes G., Lee K., Huntly B.J., Kouzarides T.;
RT "Inhibition of BET recruitment to chromatin as an effective treatment for
RT MLL-fusion leukaemia.";
RL Nature 478:529-533(2011).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=22567088; DOI=10.1371/journal.pone.0034719;
RA Nishiyama A., Dey A., Tamura T., Ko M., Ozato K.;
RT "Activation of JNK triggers release of Brd4 from mitotic chromosomes and
RT mediates protection from drug-induced mitotic stress.";
RL PLoS ONE 7:E34719-E34719(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 347-460, AND STRUCTURE BY NMR OF
RP 601-683.
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of bromodomain-containing protein 4.";
RL Submitted (AUG-2007) to the PDB data bank.
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 42-168 IN COMPLEX WITH ACETYLATED
RP HISTONE, AND X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 349-464.
RX PubMed=19828451; DOI=10.1074/jbc.m109.033712;
RA Vollmuth F., Blankenfeldt W., Geyer M.;
RT "Structures of the dual bromodomains of the P-TEFb-activating protein Brd4
RT at atomic resolution.";
RL J. Biol. Chem. 284:36547-36556(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 42-168.
RX PubMed=20715035; DOI=10.1002/anie.201002724;
RA Vollmuth F., Geyer M.;
RT "Interaction of propionylated and butyrylated histone H3 lysine marks with
RT Brd4 bromodomains.";
RL Angew. Chem. Int. Ed. 49:6768-6772(2010).
CC -!- FUNCTION: Chromatin reader protein that recognizes and binds acetylated
CC histones and plays a key role in transmission of epigenetic memory
CC across cell divisions and transcription regulation. Remains associated
CC with acetylated chromatin throughout the entire cell cycle and provides
CC epigenetic memory for postmitotic G1 gene transcription by preserving
CC acetylated chromatin status and maintaining high-order chromatin
CC structure (PubMed:10938129). During interphase, plays a key role in
CC regulating the transcription of signal-inducible genes by associating
CC with the P-TEFb complex and recruiting it to promoters. Also recruits
CC P-TEFb complex to distal enhancers, so called anti-pause enhancers in
CC collaboration with JMJD6. BRD4 and JMJD6 are required to form the
CC transcriptionally active P-TEFb complex by displacing negative
CC regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby
CC transforming it into an active form that can then phosphorylate the C-
CC terminal domain (CTD) of RNA polymerase II (By similarity). Promotes
CC phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA
CC polymerase II (PubMed:16109376). According to a report, directly acts
CC as an atypical protein kinase and mediates phosphorylation of 'Ser-2'
CC of the C-terminal domain (CTD) of RNA polymerase II; these data however
CC need additional evidences in vivo. In addition to acetylated histones,
CC also recognizes and binds acetylated RELA, leading to further
CC recruitment of the P-TEFb complex and subsequent activation of NF-
CC kappa-B. Also acts as a regulator of p53/TP53-mediated transcription:
CC following phosphorylation by CK2, recruited to p53/TP53 specific target
CC promoters (By similarity). {ECO:0000250|UniProtKB:O60885,
CC ECO:0000269|PubMed:10938129, ECO:0000269|PubMed:16109376}.
CC -!- SUBUNIT: Binds acetylated histone H4. Interacts with p53/TP53; the
CC interaction is direct (By similarity). Interacts (via CTD region) with
CC CDK9 and CCNT1, acting as an associated component of P-TEFb complex
CC (PubMed:16109376). Interacts with RELA (when acetylated at 'Lys-310').
CC Interacts (via NET domain) with NSD3, CHD4, BICRA and ATAD5. The
CC interaction with BICRA bridges BRD4 to the GBAF complex. Interacts (via
CC NET domain) with JMJD6 (via JmjC and N-terminal domains); the
CC interaction is stronger in presence of ssRNA and recruits JMJD6 on
CC distal enhancers. Interacts with NSD3 (By similarity).
CC {ECO:0000250|UniProtKB:O60885, ECO:0000269|PubMed:16109376}.
CC -!- INTERACTION:
CC Q9ESU6; Q04206: RELA; Xeno; NbExp=6; IntAct=EBI-6260864, EBI-73886;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10938129,
CC ECO:0000269|PubMed:12840145, ECO:0000269|PubMed:17267518,
CC ECO:0000269|PubMed:22567088}. Chromosome {ECO:0000269|PubMed:10938129,
CC ECO:0000269|PubMed:12840145, ECO:0000269|PubMed:17267518,
CC ECO:0000269|PubMed:22567088}. Note=Associates with acetylated chromatin
CC (PubMed:12840145). Released from chromatin upon deacetylation of
CC histones that can be triggered by different signals such as activation
CC of the JNK pathway or nocodazole treatment (PubMed:22567088).
CC Preferentially localizes to mitotic chromosomes, while it does not
CC localizes to meiotic chromosomes (PubMed:17267518).
CC {ECO:0000269|PubMed:12840145, ECO:0000269|PubMed:17267518,
CC ECO:0000269|PubMed:22567088}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=Q9ESU6-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=Q9ESU6-2; Sequence=VSP_010904, VSP_010905;
CC -!- DOMAIN: The NET domain mediates interaction with a number of chromatin
CC proteins involved in transcription regulation (NSD3, JMJD6, CHD4,
CC GLTSCR1 and ATAD5). {ECO:0000250|UniProtKB:O60885}.
CC -!- DOMAIN: The C-terminal (CTD) region mediates interaction and
CC recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex. It is
CC also required for maintenance of higher-order chromatin structure.
CC {ECO:0000250|UniProtKB:O60885}.
CC -!- DOMAIN: The 2 bromo domains mediate specific binding to acetylated
CC histones via Asn-140 and Asn-434, respectively (PubMed:19828451). The
CC exact combination of modified histone tails required to recruit BRD4 to
CC target genes is still unclear. The first bromo domain has high affinity
CC for acetylated histone H4 tail, whereas the second bromo domain
CC recognizes multiply acetylated marks in histone H3. A number of
CC specific inhibitors bind competitively to acetyl-lysine-binding
CC residues Asn-140 and Asn-434, promoting removal from acetylated
CC histones. Many of these inhibitors are benzodiazepine derivatives.
CC {ECO:0000250|UniProtKB:O60885, ECO:0000269|PubMed:19828451}.
CC -!- PTM: Phosphorylation by CK2 disrupt the intramolecular binding between
CC the bromo domain 2 and the NPS region and promotes binding between the
CC NPS and the BID regions, leading to activate the protein and promote
CC binding to acetylated histones. In absence of phosphorylation, BRD4
CC does not localize to p53/TP53 target gene promoters, phosphorylation
CC promoting recruitment to p53/TP53 target promoters.
CC {ECO:0000250|UniProtKB:O60885}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal. Embryos ndie shortly after
CC implantation and are compromised in their ability to maintain an inner
CC cell mass. {ECO:0000269|PubMed:11997514}.
CC -!- MISCELLANEOUS: Some specific inhibitors of Brd4 that prevent binding to
CC acetylated histones by binding Asn-140 and Asn-434 are promising
CC therapeutic molecules for the treatment of leukemias. JQ1, a thieno-
CC triazolo-1,4-diazepine derivative, and I-BET, a benzodiazepine
CC derivative, have been tested on tumors with success. Treatment with
CC GSK1210151A (I-BET151, a I-BET derivative) has strong effets on mixed
CC lineage leukemia and promotes myeloid differentiation and leukemia
CC stem-cell depletion (PubMed:21814200, PubMed:21964340).
CC {ECO:0000305|PubMed:21814200, ECO:0000305|PubMed:21964340}.
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DR EMBL; AF273217; AAG02191.1; -; mRNA.
DR EMBL; AF461395; AAL67833.1; -; mRNA.
DR EMBL; AF461396; AAL67834.1; -; mRNA.
DR EMBL; CT033751; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT033755; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466640; EDL40326.1; -; Genomic_DNA.
DR EMBL; CH466640; EDL40329.1; -; Genomic_DNA.
DR CCDS; CCDS37554.1; -. [Q9ESU6-2]
DR CCDS; CCDS50057.1; -. [Q9ESU6-1]
DR RefSeq; NP_065254.3; NM_020508.4. [Q9ESU6-1]
DR RefSeq; NP_932762.2; NM_198094.2. [Q9ESU6-2]
DR RefSeq; XP_006524751.1; XM_006524688.1. [Q9ESU6-1]
DR RefSeq; XP_006524752.1; XM_006524689.2. [Q9ESU6-1]
DR PDB; 2DWW; X-ray; 1.80 A; A=347-460.
DR PDB; 2JNS; NMR; -; A=601-683.
DR PDB; 3JVJ; X-ray; 1.55 A; A=42-168.
DR PDB; 3JVK; X-ray; 1.80 A; A=42-168.
DR PDB; 3JVL; X-ray; 1.20 A; A=349-464.
DR PDB; 3JVM; X-ray; 1.20 A; A=349-464.
DR PDB; 3MUK; X-ray; 1.75 A; A=42-168.
DR PDB; 3MUL; X-ray; 1.65 A; A=42-168.
DR PDBsum; 2DWW; -.
DR PDBsum; 2JNS; -.
DR PDBsum; 3JVJ; -.
DR PDBsum; 3JVK; -.
DR PDBsum; 3JVL; -.
DR PDBsum; 3JVM; -.
DR PDBsum; 3MUK; -.
DR PDBsum; 3MUL; -.
DR AlphaFoldDB; Q9ESU6; -.
DR BMRB; Q9ESU6; -.
DR SMR; Q9ESU6; -.
DR BioGRID; 208231; 5.
DR CORUM; Q9ESU6; -.
DR DIP; DIP-42181N; -.
DR IntAct; Q9ESU6; 5.
DR MINT; Q9ESU6; -.
DR STRING; 10090.ENSMUSP00000113070; -.
DR BindingDB; Q9ESU6; -.
DR ChEMBL; CHEMBL3085619; -.
DR iPTMnet; Q9ESU6; -.
DR PhosphoSitePlus; Q9ESU6; -.
DR EPD; Q9ESU6; -.
DR jPOST; Q9ESU6; -.
DR MaxQB; Q9ESU6; -.
DR PaxDb; Q9ESU6; -.
DR PRIDE; Q9ESU6; -.
DR ProteomicsDB; 265232; -. [Q9ESU6-1]
DR ProteomicsDB; 265233; -. [Q9ESU6-2]
DR Antibodypedia; 13956; 446 antibodies from 38 providers.
DR DNASU; 57261; -.
DR Ensembl; ENSMUST00000120276; ENSMUSP00000112474; ENSMUSG00000024002. [Q9ESU6-2]
DR Ensembl; ENSMUST00000121285; ENSMUSP00000113070; ENSMUSG00000024002. [Q9ESU6-1]
DR GeneID; 57261; -.
DR KEGG; mmu:57261; -.
DR UCSC; uc008bwa.3; mouse. [Q9ESU6-1]
DR CTD; 23476; -.
DR MGI; MGI:1888520; Brd4.
DR VEuPathDB; HostDB:ENSMUSG00000024002; -.
DR eggNOG; KOG1474; Eukaryota.
DR GeneTree; ENSGT00940000154549; -.
DR HOGENOM; CLU_001499_0_3_1; -.
DR InParanoid; Q9ESU6; -.
DR TreeFam; TF317345; -.
DR BRENDA; 2.7.11.23; 3474.
DR BioGRID-ORCS; 57261; 19 hits in 78 CRISPR screens.
DR ChiTaRS; Brd4; mouse.
DR EvolutionaryTrace; Q9ESU6; -.
DR PRO; PR:Q9ESU6; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9ESU6; protein.
DR Bgee; ENSMUSG00000024002; Expressed in rostral migratory stream and 272 other tissues.
DR ExpressionAtlas; Q9ESU6; baseline and differential.
DR Genevisible; Q9ESU6; MM.
DR GO; GO:0000785; C:chromatin; IDA:MGI.
DR GO; GO:0005694; C:chromosome; ISO:MGI.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
DR GO; GO:0008024; C:cyclin/CDK positive transcription elongation factor complex; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0034211; F:GTP-dependent protein kinase activity; IDA:MGI.
DR GO; GO:0070577; F:lysine-acetylated histone binding; ISS:UniProtKB.
DR GO; GO:0106140; F:P-TEFb complex binding; ISO:MGI.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0099122; F:RNA polymerase II C-terminal domain binding; IPI:MGI.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0003712; F:transcription coregulator activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0006338; P:chromatin remodeling; ISO:MGI.
DR GO; GO:0007059; P:chromosome segregation; IMP:MGI.
DR GO; GO:0044154; P:histone H3-K14 acetylation; IMP:MGI.
DR GO; GO:0043983; P:histone H4-K12 acetylation; IMP:MGI.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI.
DR GO; GO:0043922; P:negative regulation by host of viral transcription; ISO:MGI.
DR GO; GO:2000002; P:negative regulation of DNA damage checkpoint; ISO:MGI.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:2001255; P:positive regulation of histone H3-K36 trimethylation; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IPI:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:1901407; P:regulation of phosphorylation of RNA polymerase II C-terminal domain; ISS:UniProtKB.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd05497; Bromo_Brdt_I_like; 1.
DR CDD; cd05498; Bromo_Brdt_II_like; 1.
DR Gene3D; 1.20.1270.220; -; 1.
DR Gene3D; 1.20.920.10; -; 2.
DR IDEAL; IID50100; -.
DR InterPro; IPR031354; BRD4_CDT.
DR InterPro; IPR043508; Bromo_Brdt_I.
DR InterPro; IPR043509; Bromo_Brdt_II.
DR InterPro; IPR001487; Bromodomain.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR018359; Bromodomain_CS.
DR InterPro; IPR027353; NET_dom.
DR InterPro; IPR038336; NET_sf.
DR Pfam; PF17035; BET; 1.
DR Pfam; PF17105; BRD4_CDT; 1.
DR Pfam; PF00439; Bromodomain; 2.
DR PRINTS; PR00503; BROMODOMAIN.
DR SMART; SM00297; BROMO; 2.
DR SUPFAM; SSF47370; SSF47370; 2.
DR PROSITE; PS00633; BROMODOMAIN_1; 1.
DR PROSITE; PS50014; BROMODOMAIN_2; 2.
DR PROSITE; PS51525; NET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Bromodomain;
KW Chromatin regulator; Chromosome; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..1400
FT /note="Bromodomain-containing protein 4"
FT /id="PRO_0000211184"
FT DOMAIN 75..147
FT /note="Bromo 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 369..441
FT /note="Bromo 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00035"
FT DOMAIN 601..683
FT /note="NET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00857"
FT REGION 1..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 176..353
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..504
FT /note="NPS region"
FT /evidence="ECO:0000250"
FT REGION 525..580
FT /note="BID region"
FT /evidence="ECO:0000250"
FT REGION 675..1125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1050..1400
FT /note="C-terminal (CTD) region"
FT /evidence="ECO:0000250"
FT REGION 1155..1377
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 20..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..224
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 238..275
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..497
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..518
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..574
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 575..589
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..616
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 695..709
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 730..746
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..790
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 832..849
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 882..910
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 928..943
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 949..1040
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1073..1096
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1212..1228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1240..1257
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1258..1320
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1321..1361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1362..1377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 140
FT /note="Acetylated histone binding"
FT /evidence="ECO:0000269|PubMed:19828451"
FT SITE 434
FT /note="Acetylated histone binding"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 485
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 489
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 493
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 499
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 500
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 504
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 1147
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 1153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 1162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 1237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT MOD_RES 1240
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 99
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 586
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 646
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 695
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 1053
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 1147
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 1147
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT CROSSLNK 1233
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60885"
FT VAR_SEQ 721..723
FT /note="EMA -> GPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11997514"
FT /id="VSP_010904"
FT VAR_SEQ 724..1400
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11997514"
FT /id="VSP_010905"
FT MUTAGEN 139
FT /note="Y->A: No effect on acetylated histone binding."
FT /evidence="ECO:0000269|PubMed:12840145"
FT MUTAGEN 146
FT /note="I->A: No effect on acetylated histone binding."
FT /evidence="ECO:0000269|PubMed:12840145"
FT MUTAGEN 433
FT /note="Y->A: No effect on acetylated histone binding."
FT /evidence="ECO:0000269|PubMed:12840145"
FT MUTAGEN 440
FT /note="V->A: No effect on acetylated histone binding."
FT /evidence="ECO:0000269|PubMed:12840145"
FT CONFLICT 188
FT /note="A -> T (in Ref. 2; AAL67834)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="G -> S (in Ref. 2; AAL67833)"
FT /evidence="ECO:0000305"
FT CONFLICT 908
FT /note="A -> V (in Ref. 1; AAG02191)"
FT /evidence="ECO:0000305"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 97..100
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 107..116
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 122..139
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 145..160
FT /evidence="ECO:0007829|PDB:3JVJ"
FT HELIX 353..365
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 368..370
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 371..374
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 401..409
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 416..433
FT /evidence="ECO:0007829|PDB:3JVL"
FT HELIX 439..455
FT /evidence="ECO:0007829|PDB:3JVL"
FT TURN 602..605
FT /evidence="ECO:0007829|PDB:2JNS"
FT HELIX 613..623
FT /evidence="ECO:0007829|PDB:2JNS"
FT HELIX 628..631
FT /evidence="ECO:0007829|PDB:2JNS"
FT HELIX 634..639
FT /evidence="ECO:0007829|PDB:2JNS"
FT HELIX 643..645
FT /evidence="ECO:0007829|PDB:2JNS"
FT TURN 657..659
FT /evidence="ECO:0007829|PDB:2JNS"
FT HELIX 662..673
FT /evidence="ECO:0007829|PDB:2JNS"
SQ SEQUENCE 1400 AA; 155895 MW; 3D90F6D3254D5691 CRC64;
MSTESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET SNPNKPKRQT
NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI IKTPMDMGTI KKRLENNYYW
NAQECIQDFN TMFTNCYIYN KPGDDIVLMA EALEKLFLQK INELPTEETE IMIVQAKGRG
RGRKETGAAK PGVSTVPNTT QASTSPQTQT PQQNPPPPVQ ATTHPFPAVT PDLIAQPPVM
TMVPPQPLQT PSPVPPQPPP PPAPVPQPVQ SHPPIIATTP QPVKTKKGVK RKADTTTPTT
IDPIHEPPSL APEPKTAKLG PRRESSRPVK PPKKDVPDSQ QHPGPEKSSK ISEQLKCCSG
ILKEMFAKKH AAYAWPFYKP VDVEALGLHD YCDIIKHPMD MSTIKSKLES REYRDAQEFG
ADVRLMFSNC YKYNPPDHEV VAMARKLQDV FEMRFAKMPD EPEEPVVTVS SPAVPPPTKV
VAPPSSSDSS SDSSSDSDSS TDDSEEERAQ RLAELQEQLK AVHEQLAALS QPQQNKPKKK
EKDKKEKKKE KHKKKEEVEE NKKSKTKELP PKKTKKNNSS NSNVSKKEPV PTKTKPPPTY
ESEEEDKCKP MSYEEKRQLS LDINKLPGEK LGRVVHIIQS REPSLKNSNP DEIEIDFETL
KPSTLRELER YVTSCLRKKR KPQAEKVDVI AGSSKMKGFS SSESESTSES SSSDSEDSET
EMAPKSKKKG HTGRDQKKHH HHHHPQMQPA PAPVPQQPPP PPQQPPPPPP PQQQQQQPPP
PPPPPSMPQQ TAPAMKSSPP PFITAQVPVL EPQLPGSVFD PIGHFTQPIL HLPQPELPPH
LPQPPEHSTP PHLNQHAVVS PPALHNALPQ QPSRPSNRAA ALPPKPTRPP AVSPALAQPP
LLPQPPMAQP PQVLLEDEEP PAPPLTSMQM QLYLQQLQKV QPPTPLLPSV KVQSQPPPPL
PPPPHPSVQQ QQLQPQPPPP PPPQPQPPPQ QQHQPPPRPV HLPSMPFSAH IQQPPPPPGQ
QPTHPPPGQQ PPPPQPAKPQ QVIQHHPSPR HHKSDPYSAG HLREAPSPLM IHSPQMPQFQ
SLTHQSPPQQ NVQPKKQVKG RAEPQPPGPV MGQGQGCPPA SPAAVPMLSQ ELRPPSVVQP
QPLVVVKEEK IHSPIIRSEP FSTSLRPEPP KHPENIKAPV HLPQRPEMKP VDIGRPVIRP
PEQSAPPPGA PDKDKQKQEP KTPVAPKKDL KIKNMGSWAS LVQKHPTTPS STAKSSSDSF
EHFRRAAREK EEREKALKAQ AEHAEKEKER LRQERMRSRE DEDALEQARR AHEEARRRQE
QQQQQQQQRQ EQQQQQQQAA AVAAASAPQA QSSQPQSMLD QQRELARKRE QERRRREAMA
ATIDMNFQSD LLSIFEENLF
