Search Results

Overview

Uniprot IDO60885
Protein NameBromodomain-containing protein 4
Gene NameBRD4
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1050 HHSPRHHKSDPYSTG
1191 PKTPVAPKKDLKIKN
1192 KTPVAPKKDLKIKNM
1242 EEREKALKAQAEHAE
177 EIMIVQAKGRGRGRK
291 TKKGVKRKADTTTPT
317 PPEPKTTKLGQRRES
333 RPVKPPKKDVPDSQQ
585 SSNSNVSKKEPAPMK
586 SNSNVSKKEPAPMKS
694 DVIAGSSKMKGFSSS
696 IAGSSKMKGFSSSES

Function

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 (PubMed:20871596, PubMed:23086925, PubMed:23317504, PubMed:29176719, PubMed:29379197). 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 (PubMed:22334664, PubMed:23317504, PubMed:23589332). 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 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). BRD4 and JMJD6 are 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 (PubMed:16109376, PubMed:16109377, PubMed:19596240, PubMed:23589332, PubMed:24360279). Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters (By similarity). Promotes phosphorylation of 'Ser-2' of the C-terminal domain (CTD) of RNA polymerase II (PubMed:23086925). 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 (PubMed:19103749). Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters (PubMed:23317504)

Protein Sequence

10 MSAESGPGTR 20 LRNLPVMGDG 30 LETSQMSTTQ 40 AQAQPQPANA 50 ASTNPPPPET 60 SNPNKPKRQT 70 NQLQYLLRVV 80 LKTLWKHQFA 90 WPFQQPVDAV 100 KLNLPDYYKI 110 IKTPMDMGTI 120 KKRLENNYYW 130 NAQECIQDFN 140 TMFTNCYIYN 150 KPGDDIVLMA 160 EALEKLFLQK 170 INELPTEETE 180 IMIVQAKGRG 190 RGRKETGTAK 200 PGVSTVPNTT 210 QASTPPQTQT 220 PQPNPPPVQA 230 TPHPFPAVTP 240 DLIVQTPVMT 250 VVPPQPLQTP 260 PPVPPQPQPP 270 PAPAPQPVQS 280 HPPIIAATPQ 290 PVKTKKGVKR 300 KADTTTPTTI 310 DPIHEPPSLP 320 PEPKTTKLGQ 330 RRESSRPVKP 340 PKKDVPDSQQ 350 HPAPEKSSKV 360 SEQLKCCSGI 370 LKEMFAKKHA 380 AYAWPFYKPV 390 DVEALGLHDY 400 CDIIKHPMDM 410 STIKSKLEAR 420 EYRDAQEFGA 430 DVRLMFSNCY 440 KYNPPDHEVV 450 AMARKLQDVF 460 EMRFAKMPDE 470 PEEPVVAVSS 480 PAVPPPTKVV 490 APPSSSDSSS 500 DSSSDSDSST 510 DDSEEERAQR 520 LAELQEQLKA 530 VHEQLAALSQ 540 PQQNKPKKKE 550 KDKKEKKKEK 560 HKRKEEVEEN 570 KKSKAKEPPP 580 KKTKKNNSSN 590 SNVSKKEPAP 600 MKSKPPPTYE 610 SEEEDKCKPM 620 SYEEKRQLSL 630 DINKLPGEKL 640 GRVVHIIQSR 650 EPSLKNSNPD 660 EIEIDFETLK 670 PSTLRELERY 680 VTSCLRKKRK 690 PQAEKVDVIA 700 GSSKMKGFSS 710 SESESSSESS 720 SSDSEDSETE 730 MAPKSKKKGH 740 PGREQKKHHH 750 HHHQQMQQAP 760 APVPQQPPPP 770 PQQPPPPPPP 780 QQQQQPPPPP 790 PPPSMPQQAA 800 PAMKSSPPPF 810 IATQVPVLEP 820 QLPGSVFDPI 830 GHFTQPILHL 840 PQPELPPHLP 850 QPPEHSTPPH 860 LNQHAVVSPP 870 ALHNALPQQP 880 SRPSNRAAAL 890 PPKPARPPAV 900 SPALTQTPLL 910 PQPPMAQPPQ 920 VLLEDEEPPA 930 PPLTSMQMQL 940 YLQQLQKVQP 950 PTPLLPSVKV 960 QSQPPPPLPP 970 PPHPSVQQQL 980 QQQPPPPPPP 990 QPQPPPQQQH 1000 QPPPRPVHLQ 1010 PMQFSTHIQQ 1020 PPPPQGQQPP 1030 HPPPGQQPPP 1040 PQPAKPQQVI 1050 QHHHSPRHHK 1060 SDPYSTGHLR 1070 EAPSPLMIHS 1080 PQMSQFQSLT 1090 HQSPPQQNVQ 1100 PKKQELRAAS 1110 VVQPQPLVVV 1120 KEEKIHSPII 1130 RSEPFSPSLR 1140 PEPPKHPESI 1150 KAPVHLPQRP 1160 EMKPVDVGRP 1170 VIRPPEQNAP 1180 PPGAPDKDKQ 1190 KQEPKTPVAP 1200 KKDLKIKNMG 1210 SWASLVQKHP 1220 TTPSSTAKSS 1230 SDSFEQFRRA 1240 AREKEEREKA 1250 LKAQAEHAEK 1260 EKERLRQERM 1270 RSREDEDALE 1280 QARRAHEEAR 1290 RRQEQQQQQR 1300 QEQQQQQQQQ 1310 AAAVAAAATP 1320 QAQSSQPQSM 1330 LDQQRELARK 1340 REQERRRREA 1350 MAATIDMNFQ 1360 SDLLSIFEEN LF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005694 chromosome
Cellular Component GO:0000794 condensed nuclear chromosome
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0019899 enzyme binding
Molecular Function GO:0042393 histone binding
Molecular Function GO:0140119 histone H3K27ac reader activity
Molecular Function GO:0140072 histone H3K9ac reader activity
Molecular Function GO:0140008 histone H4 reader activity
Molecular Function GO:0140011 histone H4K12ac reader activity
Molecular Function GO:0140046 histone H4K16ac reader activity
Molecular Function GO:0140012 histone H4K5ac reader activity
Molecular Function GO:0140055 histone H4K8ac reader activity
Molecular Function GO:0106140 P-TEFb complex binding
Molecular Function GO:0002039 p53 binding
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0099122 RNA polymerase II C-terminal domain binding
Molecular Function GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
Molecular Function GO:0000976 transcription cis-regulatory region binding
Molecular Function GO:0003713 transcription coactivator activity
Molecular Function GO:0003712 transcription coregulator activity
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0043922 host-mediated suppression of viral transcription
Biological Process GO:2000002 negative regulation of DNA damage checkpoint
Biological Process GO:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
Biological Process GO:2000330 positive regulation of T-helper 17 cell lineage commitment
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0032968 positive regulation of transcription elongation by RNA polymerase II
Biological Process GO:0050727 regulation of inflammatory response
Biological Process GO:0006357 regulation of transcription by RNA polymerase II

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[3] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[4] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.