O60885 · BRD4_HUMAN
- ProteinBromodomain-containing protein 4
- GeneBRD4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1362 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Isoform B
Miscellaneous
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 (Probable) (PubMed:21964340).
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).
Activity regulation
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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 140 | Acetylated histone binding | ||||
Sequence: N | ||||||
Site | 433 | Acetylated histone binding | ||||
Sequence: N | ||||||
Site | 719-720 | Breakpoint for translocation to form BDR4-NUTM1 fusion protein | ||||
Sequence: TE |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBromodomain-containing protein 4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO60885
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
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).
Isoform B
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Cornelia de Lange syndrome 6 (CDLS6)
- Note
- DescriptionA 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.
- See alsoMIM:620568
Natural variants in CDLS6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089193 | 430 | Y>C | in CDLS6; likely pathogenic; reduced acetylated histone binding |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041919 | 37 | in dbSNP:rs35177876 | |||
Sequence: P → S | ||||||
Mutagenesis | 140 | Abolishes binding to acetylated histones. | ||||
Sequence: N → A | ||||||
Natural variant | VAR_089189 | 145 | found in a patient with a neurodevelopmental syndrome; uncertain significance | |||
Sequence: D → G | ||||||
Natural variant | VAR_089190 | 235-1362 | found in a patient with a neurodevelopmental syndrome; likely pathogenic | |||
Sequence: Missing | ||||||
Natural variant | VAR_089191 | 295 | found in a patient with a neurodevelopmental syndrome; uncertain significance | |||
Sequence: T → P | ||||||
Natural variant | VAR_041920 | 371 | in dbSNP:rs55805532 | |||
Sequence: A → G | ||||||
Natural variant | VAR_089192 | 390 | found in a patient with a neurodevelopmental syndrome; uncertain significance | |||
Sequence: Y → C | ||||||
Natural variant | VAR_089193 | 430 | in CDLS6; likely pathogenic; reduced acetylated histone binding | |||
Sequence: Y → C | ||||||
Mutagenesis | 433 | Abolishes binding to acetylated histones. | ||||
Sequence: N → A | ||||||
Mutagenesis | 492-494 | Impaired phosphorylation by CK2 and binding to acetylated histones. | ||||
Sequence: SSS → ASA | ||||||
Mutagenesis | 498-500 | Impaired phosphorylation by CK2 and binding to acetylated histones. | ||||
Sequence: SST → AAA | ||||||
Mutagenesis | 503 | Impaired phosphorylation by CK2 and binding to acetylated histones. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_041921 | 563 | in dbSNP:rs55970906 | |||
Sequence: S → N | ||||||
Natural variant | VAR_041922 | 598 | in dbSNP:rs34362023 | |||
Sequence: T → S | ||||||
Mutagenesis | 651-653 | Decreases interaction with JMJD6 and NSD3.No effect on interaction with histone 4 acetylated. | ||||
Sequence: EIE → AIA | ||||||
Natural variant | VAR_041923 | 669 | in dbSNP:rs35824241 | |||
Sequence: R → H | ||||||
Natural variant | VAR_048427 | 1097 | in dbSNP:rs35676845 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2,402 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, cross-link, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000211183 | 1-1362 | UniProt | Bromodomain-containing protein 4 | |||
Sequence: MSAESGPGTRLRNLPVMGDGLETSQMSTTQAQAQPQPANAASTNPPPPETSNPNKPKRQTNQLQYLLRVVLKTLWKHQFAWPFQQPVDAVKLNLPDYYKIIKTPMDMGTIKKRLENNYYWNAQECIQDFNTMFTNCYIYNKPGDDIVLMAEALEKLFLQKINELPTEETEIMIVQAKGRGRGRKETGTAKPGVSTVPNTTQASTPPQTQTPQPNPPPVQATPHPFPAVTPDLIVQTPVMTVVPPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPIIAATPQPVKTKKGVKRKADTTTPTTIDPIHEPPSLPPEPKTTKLGQRRESSRPVKPPKKDVPDSQQHPAPEKSSKVSEQLKCCSGILKEMFAKKHAAYAWPFYKPVDVEALGLHDYCDIIKHPMDMSTIKSKLEAREYRDAQEFGADVRLMFSNCYKYNPPDHEVVAMARKLQDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQEQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEEDKCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKMKGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF | |||||||
Cross-link | 99 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 296 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 338 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 469 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 470 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 470 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 484 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 488 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 492 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 494 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 498 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 499 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Modified residue | 503 | UniProt | Phosphoserine; by CK2 | ||||
Sequence: S | |||||||
Cross-link | 585 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 593 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 598 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 601 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 601 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 645 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Cross-link | 694 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 1045 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 1050 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 1051 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1055 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1064 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1070 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1074 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1078 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1083 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1100 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1111 | UniProt | N6-acetyllysine; alternate | ||||
Sequence: K | |||||||
Cross-link | 1111 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternate | ||||
Sequence: K | |||||||
Cross-link | 1111 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | |||||||
Modified residue | 1117 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1117 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1126 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1126 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1128 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 1197 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 1201 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1201 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1204 | UniProt | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex (PubMed:16109376, PubMed:16109377, PubMed:23317504, PubMed:24360279).
Interacts with RELA (when acetylated at 'Lys-310') (PubMed:19103749).
Interacts (via NET domain) with NSD3, CHD4, BICRA and ATAD5 (PubMed:21555454, PubMed:29176719).
The interaction with BICRA bridges BRD4 to the GBAF complex (PubMed:16109376, PubMed:16109377, PubMed:19103749, PubMed:21555454, PubMed:23317504, PubMed:29374058).
Interacts (via NET domain) with JMJD6 (via JmjC and N-terminal domains); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers (PubMed:21555454, PubMed:24360279, PubMed:29176719).
Interacts with NSD3 (PubMed:29176719).
Interacts with NIPBL (By similarity).
Isoform B
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-58 | Disordered | ||||
Sequence: MSAESGPGTRLRNLPVMGDGLETSQMSTTQAQAQPQPANAASTNPPPPETSNPNKPKR | ||||||
Compositional bias | 20-39 | Polar residues | ||||
Sequence: GLETSQMSTTQAQAQPQPAN | ||||||
Domain | 75-147 | Bromo 1 | ||||
Sequence: WKHQFAWPFQQPVDAVKLNLPDYYKIIKTPMDMGTIKKRLENNYYWNAQECIQDFNTMFTNCYIYNKPGDDIV | ||||||
Region | 174-229 | Disordered | ||||
Sequence: VQAKGRGRGRKETGTAKPGVSTVPNTTQASTPPQTQTPQPNPPPVQATPHPFPAVT | ||||||
Compositional bias | 191-207 | Polar residues | ||||
Sequence: PGVSTVPNTTQASTPPQ | ||||||
Compositional bias | 208-224 | Pro residues | ||||
Sequence: TQTPQPNPPPVQATPHP | ||||||
Region | 242-352 | Disordered | ||||
Sequence: VPPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPIIAATPQPVKTKKGVKRKADTTTPTTIDPIHEPPSLPPEPKTTKLGQRRESSRPVKPPKKDVPDSQQHPAPEKSSKVSE | ||||||
Compositional bias | 243-274 | Pro residues | ||||
Sequence: PPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPI | ||||||
Compositional bias | 316-340 | Basic and acidic residues | ||||
Sequence: TKLGQRRESSRPVKPPKKDVPDSQQ | ||||||
Domain | 368-440 | Bromo 2 | ||||
Sequence: KHAAYAWPFYKPVDVEALGLHDYCDIIKHPMDMSTIKSKLEAREYRDAQEFGADVRLMFSNCYKYNPPDHEVV | ||||||
Region | 463-615 | Disordered | ||||
Sequence: EPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQEQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEEDKCKPMSYEEK | ||||||
Compositional bias | 482-496 | Polar residues | ||||
Sequence: PPSSSDSSSDSSSDS | ||||||
Region | 484-503 | NPS region | ||||
Sequence: SSSDSSSDSSSDSDSSTDDS | ||||||
Compositional bias | 503-517 | Basic and acidic residues | ||||
Sequence: SEEERAQRLAELQEQ | ||||||
Region | 524-579 | BID region | ||||
Sequence: QLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSS | ||||||
Compositional bias | 549-573 | Basic and acidic residues | ||||
Sequence: EKHKRKEEVEENKKSKAKEPPPKKT | ||||||
Compositional bias | 597-615 | Basic and acidic residues | ||||
Sequence: PTYESEEEDKCKPMSYEEK | ||||||
Domain | 600-682 | NET | ||||
Sequence: ESEEEDKCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQ | ||||||
Region | 674-1100 | Disordered | ||||
Sequence: CLRKKRKPQAEKVDVIAGSSKMKGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAAS | ||||||
Compositional bias | 694-708 | Polar residues | ||||
Sequence: KMKGFSSSESESSSE | ||||||
Compositional bias | 729-745 | Basic residues | ||||
Sequence: GHPGREQKKHHHHHHQQ | ||||||
Compositional bias | 751-788 | Pro residues | ||||
Sequence: APVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQ | ||||||
Compositional bias | 830-847 | Pro residues | ||||
Sequence: LPQPELPPHLPQPPEHST | ||||||
Compositional bias | 926-941 | Polar residues | ||||
Sequence: MQMQLYLQQLQKVQPP | ||||||
Compositional bias | 947-999 | Pro residues | ||||
Sequence: SVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHL | ||||||
Compositional bias | 1012-1036 | Pro residues | ||||
Sequence: PPPQGQQPPHPPPGQQPPPPQPAKP | ||||||
Region | 1047-1362 | C-terminal (CTD) region | ||||
Sequence: RHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF | ||||||
Compositional bias | 1068-1094 | Polar residues | ||||
Sequence: IHSPQMSQFQSLTHQSPPQQNVQPKKQ | ||||||
Region | 1116-1339 | Disordered | ||||
Sequence: HSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRRE | ||||||
Compositional bias | 1176-1192 | Basic and acidic residues | ||||
Sequence: DKDKQKQEPKTPVAPKK | ||||||
Compositional bias | 1204-1224 | Polar residues | ||||
Sequence: SLVQKHPTTPSSTAKSSSDSF | ||||||
Compositional bias | 1225-1287 | Basic and acidic residues | ||||
Sequence: EQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQ | ||||||
Compositional bias | 1288-1323 | Polar residues | ||||
Sequence: QQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQ | ||||||
Compositional bias | 1324-1339 | Basic and acidic residues | ||||
Sequence: QRELARKREQERRRRE |
Domain
It is also required for maintenance of higher-order chromatin structure (PubMed:22334664).
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:22136404, PubMed:22137933, PubMed:23517011, PubMed:23530754).
Isoform B
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
O60885-1
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.
- NameA
- SynonymsBrd4L, Long
- Length1,362
- Mass (Da)152,219
- Last updated2002-01-31 v2
- ChecksumD52EFE1CF9960907
O60885-2
- NameC
- SynonymsBrd4S, Short
O60885-3
- NameB
- Differences from canonical
- 720-1362: EMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF → AFCTSGDFVSPGPSPYHSHVQCGRFREMLRWFLVDVEQTAAGQPHRQSAAGPAITWAPAIAYPSPECARCCVGCS
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 20-39 | Polar residues | ||||
Sequence: GLETSQMSTTQAQAQPQPAN | ||||||
Compositional bias | 191-207 | Polar residues | ||||
Sequence: PGVSTVPNTTQASTPPQ | ||||||
Compositional bias | 208-224 | Pro residues | ||||
Sequence: TQTPQPNPPPVQATPHP | ||||||
Compositional bias | 243-274 | Pro residues | ||||
Sequence: PPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPI | ||||||
Compositional bias | 316-340 | Basic and acidic residues | ||||
Sequence: TKLGQRRESSRPVKPPKKDVPDSQQ | ||||||
Compositional bias | 482-496 | Polar residues | ||||
Sequence: PPSSSDSSSDSSSDS | ||||||
Compositional bias | 503-517 | Basic and acidic residues | ||||
Sequence: SEEERAQRLAELQEQ | ||||||
Compositional bias | 549-573 | Basic and acidic residues | ||||
Sequence: EKHKRKEEVEENKKSKAKEPPPKKT | ||||||
Compositional bias | 597-615 | Basic and acidic residues | ||||
Sequence: PTYESEEEDKCKPMSYEEK | ||||||
Compositional bias | 694-708 | Polar residues | ||||
Sequence: KMKGFSSSESESSSE | ||||||
Alternative sequence | VSP_010902 | 720-722 | in isoform C | |||
Sequence: EMA → GPA | ||||||
Alternative sequence | VSP_047671 | 720-1362 | in isoform B | |||
Sequence: EMAPKSKKKGHPGREQKKHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVHLPQRPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF → AFCTSGDFVSPGPSPYHSHVQCGRFREMLRWFLVDVEQTAAGQPHRQSAAGPAITWAPAIAYPSPECARCCVGCS | ||||||
Alternative sequence | VSP_010903 | 723-1362 | in isoform C | |||
Sequence: Missing | ||||||
Compositional bias | 729-745 | Basic residues | ||||
Sequence: GHPGREQKKHHHHHHQQ | ||||||
Compositional bias | 751-788 | Pro residues | ||||
Sequence: APVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQ | ||||||
Compositional bias | 830-847 | Pro residues | ||||
Sequence: LPQPELPPHLPQPPEHST | ||||||
Compositional bias | 926-941 | Polar residues | ||||
Sequence: MQMQLYLQQLQKVQPP | ||||||
Compositional bias | 947-999 | Pro residues | ||||
Sequence: SVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHL | ||||||
Compositional bias | 1012-1036 | Pro residues | ||||
Sequence: PPPQGQQPPHPPPGQQPPPPQPAKP | ||||||
Compositional bias | 1068-1094 | Polar residues | ||||
Sequence: IHSPQMSQFQSLTHQSPPQQNVQPKKQ | ||||||
Compositional bias | 1176-1192 | Basic and acidic residues | ||||
Sequence: DKDKQKQEPKTPVAPKK | ||||||
Compositional bias | 1204-1224 | Polar residues | ||||
Sequence: SLVQKHPTTPSSTAKSSSDSF | ||||||
Compositional bias | 1225-1287 | Basic and acidic residues | ||||
Sequence: EQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQ | ||||||
Compositional bias | 1288-1323 | Polar residues | ||||
Sequence: QQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQ | ||||||
Compositional bias | 1324-1339 | Basic and acidic residues | ||||
Sequence: QRELARKREQERRRRE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF386649 EMBL· GenBank· DDBJ | AAL26987.1 EMBL· GenBank· DDBJ | mRNA | ||
Y12059 EMBL· GenBank· DDBJ | CAA72780.1 EMBL· GenBank· DDBJ | mRNA | ||
AC004798 EMBL· GenBank· DDBJ | AAC27978.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
AC003111 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC005776 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471106 EMBL· GenBank· DDBJ | EAW84470.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC035266 EMBL· GenBank· DDBJ | AAH35266.1 EMBL· GenBank· DDBJ | mRNA | ||
AY166680 EMBL· GenBank· DDBJ | AAO22237.1 EMBL· GenBank· DDBJ | mRNA | Different termination. |