CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001019
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Bromodomain-containing protein 4 
Protein Synonyms/Alias
 Protein HUNK1 
Gene Name
 BRD4 
Gene Synonyms/Alias
 HUNK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
99LNLPDYYKIIKTPMDubiquitination[1, 2]
112MDMGTIKKRLENNYYubiquitination[3]
362KCCSGILKEMFAKKHacetylation[4]
367ILKEMFAKKHAAYAWacetylation[4]
368LKEMFAKKHAAYAWPacetylation[4]
685KRKPQAEKVDVIAGSacetylation[5]
1111PQPLVVVKEEKIHSPacetylation[5, 6, 7, 8]
1111PQPLVVVKEEKIHSPsumoylation[9]
1177PPPGAPDKDKQKQEPacetylation[8]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [7] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [8] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [9] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 75 147 Bromo 1.
 DOMAIN 368 440 Bromo 2.
 DOMAIN 600 682 NET.
 REGION 484 503 NPS region.
 REGION 524 579 BID region.
 REGION 1047 1362 C-terminal (CTD) region.
 BINDING 140 140 Acetylated histones.
 BINDING 140 140 Inhibitor.
 BINDING 433 433 Acetylated histones.
 BINDING 433 433 Inhibitor.
 MOD_RES 470 470 Phosphoserine.
 MOD_RES 484 484 Phosphoserine; by CK2.
 MOD_RES 488 488 Phosphoserine; by CK2.
 MOD_RES 492 492 Phosphoserine; by CK2.
 MOD_RES 498 498 Phosphoserine; by CK2.
 MOD_RES 499 499 Phosphoserine; by CK2.
 MOD_RES 503 503 Phosphoserine; by CK2.
 MOD_RES 598 598 Phosphothreonine (By similarity).
 MOD_RES 601 601 Phosphoserine.
 MOD_RES 1045 1045 Phosphoserine (By similarity).
 MOD_RES 1111 1111 N6-acetyllysine.
 MOD_RES 1117 1117 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Bromodomain; Chromatin regulator; Chromosomal rearrangement; Chromosome; Complete proteome; DNA damage; Host-virus interaction; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Transcription; Transcription regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1362 AA 
Protein Sequence
MSAESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET SNPNKPKRQT 60
NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI IKTPMDMGTI KKRLENNYYW 120
NAQECIQDFN TMFTNCYIYN KPGDDIVLMA EALEKLFLQK INELPTEETE IMIVQAKGRG 180
RGRKETGTAK PGVSTVPNTT QASTPPQTQT PQPNPPPVQA TPHPFPAVTP DLIVQTPVMT 240
VVPPQPLQTP PPVPPQPQPP PAPAPQPVQS HPPIIAATPQ PVKTKKGVKR KADTTTPTTI 300
DPIHEPPSLP PEPKTTKLGQ RRESSRPVKP PKKDVPDSQQ HPAPEKSSKV SEQLKCCSGI 360
LKEMFAKKHA AYAWPFYKPV DVEALGLHDY CDIIKHPMDM STIKSKLEAR EYRDAQEFGA 420
DVRLMFSNCY KYNPPDHEVV AMARKLQDVF EMRFAKMPDE PEEPVVAVSS PAVPPPTKVV 480
APPSSSDSSS DSSSDSDSST DDSEEERAQR LAELQEQLKA VHEQLAALSQ PQQNKPKKKE 540
KDKKEKKKEK HKRKEEVEEN KKSKAKEPPP KKTKKNNSSN SNVSKKEPAP MKSKPPPTYE 600
SEEEDKCKPM SYEEKRQLSL DINKLPGEKL GRVVHIIQSR EPSLKNSNPD EIEIDFETLK 660
PSTLRELERY VTSCLRKKRK PQAEKVDVIA GSSKMKGFSS SESESSSESS SSDSEDSETE 720
MAPKSKKKGH PGREQKKHHH HHHQQMQQAP APVPQQPPPP PQQPPPPPPP QQQQQPPPPP 780
PPPSMPQQAA PAMKSSPPPF IATQVPVLEP QLPGSVFDPI GHFTQPILHL PQPELPPHLP 840
QPPEHSTPPH LNQHAVVSPP ALHNALPQQP SRPSNRAAAL PPKPARPPAV SPALTQTPLL 900
PQPPMAQPPQ VLLEDEEPPA PPLTSMQMQL YLQQLQKVQP PTPLLPSVKV QSQPPPPLPP 960
PPHPSVQQQL QQQPPPPPPP QPQPPPQQQH QPPPRPVHLQ PMQFSTHIQQ PPPPQGQQPP 1020
HPPPGQQPPP PQPAKPQQVI QHHHSPRHHK SDPYSTGHLR EAPSPLMIHS PQMSQFQSLT 1080
HQSPPQQNVQ PKKQELRAAS VVQPQPLVVV KEEKIHSPII RSEPFSPSLR PEPPKHPESI 1140
KAPVHLPQRP EMKPVDVGRP VIRPPEQNAP PPGAPDKDKQ KQEPKTPVAP KKDLKIKNMG 1200
SWASLVQKHP TTPSSTAKSS SDSFEQFRRA AREKEEREKA LKAQAEHAEK EKERLRQERM 1260
RSREDEDALE QARRAHEEAR RRQEQQQQQR QEQQQQQQQQ AAAVAAAATP QAQSSQPQSM 1320
LDQQRELARK REQERRRREA MAATIDMNFQ SDLLSIFEEN LF 1362 
Gene Ontology
 GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0000790; C:nuclear chromatin; IEA:Compara.
 GO:0003677; F:DNA binding; IEA:Compara.
 GO:0007059; P:chromosome segregation; IEA:Compara.
 GO:0044154; P:histone H3-K14 acetylation; IEA:Compara.
 GO:0043983; P:histone H4-K12 acetylation; IEA:Compara.
 GO:0001833; P:inner cell mass cell proliferation; IEA:Compara.
 GO:0043388; P:positive regulation of DNA binding; IEA:Compara.
 GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:MGI.
 GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IMP:MGI.
 GO:0006468; P:protein phosphorylation; IEA:Compara.
 GO:0000114; P:regulation of transcription involved in G1 phase of mitotic cell cycle; IMP:MGI.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR001487; Bromodomain.
 IPR018359; Bromodomain_CS.
 IPR027353; NET_dom. 
Pfam
 PF00439; Bromodomain 
SMART
 SM00297; BROMO 
PROSITE
 PS00633; BROMODOMAIN_1
 PS50014; BROMODOMAIN_2
 PS51525; NET 
PRINTS
 PR00503; BROMODOMAIN.