BRD4
entrez
23476
canonical
uniprot
O60885
canonical
ensembl
ENSG00000141867
resolver
ensp
ENSP00000263377
resolver
ensp
ENSP00000353112
resolver
ensp
ENSP00000360901
resolver
ensp
ENSP00000506350
resolver
ensp
ENSP00000679074
resolver
genesymbol
BRD4
resolver
genesymbol_syn
HUNK1
resolver
hgnc
HGNC:13575
resolver
uniprot
O60433
resolver
uniprot
Q4G0X8
resolver
uniprot
Q86YS8
resolver
uniprot
Q96PD3
resolver
uniprot_entry
BRD4_HUMAN
resolver
uniprot_sec
O60433
resolver
uniprot_sec
Q4G0X8
resolver
uniprot_sec
Q86YS8
resolver
uniprot_sec
Q96PD3
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by JQ1, a thieno-triazolo-1,4-diazepine derivative, which specifically inhibits members of the BET family (BRD2, BRD3 and BRD4) (PubMed:20871596). The first bromo domain is inhibited by GSK778 (iBET-BD1), which specifically inhibits the first bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:32193360). The second bromo domain is inhibited by ABBV-744, which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:31969702). The second bromo domain is inhibited by GSK046 (iBET-BD2), which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4) (PubMed:32193360). {ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:31969702, ECO:0000269|PubMed:32193360}.
uniprot
proteins
amino_acid_sequence
MSAESGPGTRLRNLPVMGDGLETSQMSTTQAQAQPQPANAASTNPPPPETSNPNKPKRQTNQLQYLLRVVLKTLWKHQFAWPFQQPVDAVKLNLPDYYKIIKTPMDMGTIKKRLENNYYWNAQECIQDFNTMFTNCYIYNKPGDDIVLMAEALEKLFLQKINELPTEETEIMIVQAKGRGRGRKETGTAKPGVSTVPNTTQASTPPQTQTPQPNPPPVQATPHPFPAVTPDLIVQTPVMTVVPPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPIIAATPQPVKTKKGVKRKADTTTPTTIDPIHEPPSLPPEPKTTKLGQRRESSRPVKPPKKDVPDSQQHPAPEKSSKVSEQLKCCSGILKEMFAKKHAAYAWPFYKPVDVEALGLHDYCDIIKHPMDMSTIKSKLEAREYRDAQEFGADVRLMFSNCYKYNPPDHEVVAMARKLQDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQEQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEEDKCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKMKGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF
uniprot
proteins
disease_involvement
DISEASE: Cornelia de Lange syndrome 6 (CDLS6) [MIM:620568]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. CDLS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:29379197, ECO:0000269|PubMed:35470444}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=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 NUTM1 which produces a BRD4-NUTM1 fusion protein. {ECO:0000269|PubMed:11733348, ECO:0000269|PubMed:12543779}.
uniprot
proteins
function
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 evidence 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). {ECO:0000250|UniProtKB:Q9ESU6, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:19596240, ECO:0000269|PubMed:22334664, ECO:0000269|PubMed:22509028, ECO:0000269|PubMed:23086925, ECO:0000269|PubMed:23317504, ECO:0000269|PubMed:23589332, ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:29176719}.; FUNCTION: [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 H2AX/H2A.x phosphorylation. {ECO:0000269|PubMed:23728299}.
uniprot
proteins
mass_dalton
152219
uniprot
proteins
mutagenesis
MUTAGEN 140; /note="N->A: Abolishes binding to acetylated histones."; /evidence="ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:23728299"; MUTAGEN 433; /note="N->A: Abolishes binding to acetylated histones."; /evidence="ECO:0000269|PubMed:22464331"; MUTAGEN 492..494; /note="SSS->ASA: Impaired phosphorylation by CK2 and binding to acetylated histones."; /evidence="ECO:0000269|PubMed:23317504"; MUTAGEN 498..500; /note="SST->AAA: Impaired phosphorylation by CK2 and binding to acetylated histones."; /evidence="ECO:0000269|PubMed:23317504"; MUTAGEN 503; /note="S->A: Impaired phosphorylation by CK2 and binding to acetylated histones."; /evidence="ECO:0000269|PubMed:23317504"; MUTAGEN 651..653; /note="EIE->AIA: Decreases interaction with JMJD6 and NSD3. No effect on interaction with histone 4 acetylated."; /evidence="ECO:0000269|PubMed:29176719
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:23317504}.
uniprot
proteins
protein_family
BET family
uniprot
proteins
pubmed
11733348
uniprot
proteins
pubmed
12543779
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16109376
uniprot
proteins
pubmed
16109377
uniprot
proteins
pubmed
16940503
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17189189
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18500820
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18922874
uniprot
proteins
pubmed
19103749
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19596240
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20871596
uniprot
proteins
pubmed
21068722
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21555454
uniprot
proteins
pubmed
21568322
uniprot
proteins
pubmed
21890894
uniprot
proteins
pubmed
21964340
uniprot
proteins
pubmed
22136404
uniprot
proteins
pubmed
22137933
uniprot
proteins
pubmed
22334664
uniprot
proteins
pubmed
22464331
uniprot
proteins
pubmed
22509028
uniprot
proteins
pubmed
22645123
uniprot
proteins
pubmed
23086925
uniprot
proteins
pubmed
23095041
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23317504
uniprot
proteins
pubmed
23517011
uniprot
proteins
pubmed
23530754
uniprot
proteins
pubmed
23589332
uniprot
proteins
pubmed
23728299
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24360279
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25593309
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29176719
uniprot
proteins
pubmed
29374058
uniprot
proteins
pubmed
29379197
uniprot
proteins
pubmed
29440723
uniprot
proteins
pubmed
31168063
uniprot
proteins
pubmed
31969702
uniprot
proteins
pubmed
32193360
uniprot
proteins
pubmed
35470444
uniprot
proteins
sequence_length
1362
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:25593309}. Chromosome {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:21890894}. Note=Associates with acetylated chromatin (PubMed:16109376, PubMed:21890894). Released from chromatin upon deacetylation of histones that can be triggered by different signals such as activation of the JNK pathway or nocodazole treatment (PubMed:16109376, PubMed:21890894). Preferentially localizes to mitotic chromosomes, while it does not localize to meiotic chromosomes (PubMed:16109376, PubMed:21890894). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:21890894}.; SUBCELLULAR LOCATION: [Isoform B]: Chromosome {ECO:0000269|PubMed:23728299}.
uniprot
proteins