CODSWALLOP

Bromodomain-containing protein 4

Homo sapiens · seed O60885 · 1362 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

1,996Entries 2,000Entities 314Constructs 13Organisms 1,323Ligand-bound
0.91 ÅBest res.
1.69 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

9KEM, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 9KEM
9KEM at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

168113621204 constructs

Constructs, most-used first

314 distinct constructs across 1,996 entries. 1,997 polymer entities differ from the UniProt canonical sequence in some way, 1 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
310 127 0.94 4QB3 residues 42-168; T43M
297 156 1.33 5PQI residues 529-688; 2 internal deletions; R529M, D531H, L532H +18 more
199 138 1.49 5PG1 residues 2034-2168; 3-residue insertion after 2052; K2034M, K2035H, R2036H +16 more
118 149 1.09 5S9G residues 1297-1440; 5-residue insertion after 1305; T1297M, R1298H, K1299H +13 more
58 119 1.05 5J0D residues 1079-1197; Q1079S, P1080M
39 115 1.28 7NPZ residues 341-455; S341G, K342S, K343M
31 141 1.28 8K14 residues 28-168; T28M, T29K, Q30K +13 more
29 129 0.99 7Z9W residues 40-168; A40G, A41S, S42H +1 more
27 125 1.20 6JJ5 residues 43-167; T43M
26 117 1.70 4IR5 residues 2052-2168; F2052S, T2053M
25 105 1.09 7BLA residues 1794-1898; N1794S, H1795M, E1845H +1 more
22 123 1.05 5R4O residues 2915-3037; C2915S, Q2916M
20 109 1.35 5UF0 residues 349-457; K349S, V350H, S351M
20 123 1.35 6V1B residues 128-250; A128S, C129M, R130L +13 more
19 105 1.30 7BL9 residues 1794-1898; N1794S, H1795M
19 128 1.18 5S8F residues 1313-1440; A1313S, Q1314M
18 116 1.65 5DYU residues 2052-2167; F2052S, T2053M
15 119 1.68 5MKX residues 713-831; P713S, S714M
14 122 1.50 6JKE residues 73-194
14 126 1.13 9F1J residues 43-168; T43M
12 114 1.20 5O38 residues 342-455; K342S, K343M, L383V
12 116 1.40 4OUF residues 1082-1197
12 124 1.43 4HXS residues 43-166; T43M
12 154 1.60 4ALG residues 47-200; T47G, M48S, A49S +16 more
11 113 1.39 7MRD residues 25-137; N25G, G26A, R27A +1 more

Showing the 25 most-used of 314.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

Y372I 70% M442A 70% P434A 69% S358R 69% K355R 68% M425I 67% K404R 67% M364L 66% R453E 66% K445R 66% S351T 65% I403M 61% K332T 59% P331G 57% K329D 56% R444H 56% K431T 56% I360V 56% D448K 56% L446M 55% D334N 54% E363Q 53% H396K 52% D381N 52% A443G 52% A409S 52% I393H 51% E345H 49% A455T 49% R423D 47%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 1,722 86.3%
dimeric2 191 9.6%
trimeric3 36 1.8%
tetrameric4 27 1.4%
undecameric11 11 0.6%
hexameric6 3 0.2%
octameric8 2 0.1%
27-meric27 1 0.1%

955 entries have the depositor's assembly corroborated by PISA, 982 carry the depositor's word alone and 59 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 22 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 2DVQ, 2DVR, 2DVS, 2FSA, 3AQA, 3HMF, 3ONI, 4QC3, 4QEV, 4QEW, 5TWX, 5VBR, 5XZC, 6V1B, 7L9J, 7RJM, 7TUQ, 7TV0, 8B5B, 8CV4.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHBromodomain-likeSCOP2BBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomainBromodomain16811362
DomainSourceSpan (seed)Chains
Bromodomain-likeCATH 1.20.920.10 358–468 1,411
Zinc/RING finger domain, C3HC4 (zinc finger)CATH 3.30.40.10 491–499 31
BromodomainSCOP2B 8084245 60–165 519
BromodomainSCOP2B 8097864 61–176 53
BromodomainSCOP2B 8033300 69–176 22
BromodomainSCOP2B 8084225 73–188 42
BromodomainSCOP2B 8084255 355–462 93
BromodomainSCOP2B 8084237 356–458 54
BromodomainSCOP2B 8084235 374–486 258
BromodomainSCOP2B 8084285 378–477 52
BromodomainSCOP2B 8084279 379–494 141
BromodomainSCOP2B 8040939 380–493 113

What binds it

DQW DQW8 entries R78 R787 entries BMF BMF7 entries JQ1 JQ16 entries 1K0 1K06 entries VYJ VYJ6 entries N6I N6I6 entries EAM EAM5 entries 3PF 3PF5 entries 2LO 2LO5 entries COA COA5 entries 79C 79C5 entries
ComponentClassNameEntriesBest (Å)
EDOcryoprotectant 1,2-Ethanediol 1,030 0.94
NAion Sodium Ion 348 1.16
GOLcryoprotectant Glycerol 132 0.91
DMScryoprotectant Dimethyl Sulfoxide 84 1.05
SO4ion Sulfate Ion 61 1.15
ZNion Zinc Ion 57 1.14
CLion Chloride Ion 51 0.91
PEGcryoprotectant Di(Hydroxyethyl)ether 28 1.04
NO3ion Nitrate Ion 25 1.42
MGion Magnesium Ion 19 1.62
FMTbuffer Formic Acid 17 1.20
ACTcryoprotectant Acetate Ion 15 1.07
BU3cryoprotectant (R,r)-2,3-Butanediol 14 1.25
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 12 1.59
NIion Nickel (Ii) Ion 11 1.10
Kion Potassium Ion 11 1.23
SCNion Thiocyanate Ion 9 1.05
PGEcryoprotectant Triethylene Glycol 9 0.94
CAion Calcium Ion 9 1.07
NH2solvent Amino Group 9 1.47

How it crystallises

Parsed from the free text 1,918 depositors typed into _exptl_crystal_grow.pdbx_details, out of 1,926 entries that recorded anything at all. Median pH 7.0 (range 3.5 to 10.5).

Precipitants

PEG × Sodium chloride × Ammonium sulfate × Magnesium chloride × Sodium formate × Lithium sulfate × MPD × Sodium citrate × PEG (unspecified) × Ethanol × Sodium malonate × Calcium chloride × Isopropanol × Tacsimate ×

Buffers

Bis-Tris × MES × Tris × HEPES × Phosphate × Bis-Tris propane × Citrate × Sodium acetate × Sodium cacodylate × Imidazole × Succinate × CAPS × Glycine ×

Which entries to trust

1,995 entries carry a wwPDB validation report: 1,249 clean, 659 worth a check and 87 with something to explain. Median clashscore 2.93, median RSRZ outliers 3.48%, median R-free minus R-work 0.033. 1,981 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens1,944 0.91 1296 53%
Mus musculus21 1.20 9 24%
Nakaseomyces glabratus6 1.08 4 15%
Plasmodium falciparum 3D76 1.56 2 13%
Candida albicans4 1.20 2 16%
Plasmodium vivax4 1.61 4 7%
Thermochaetoides thermophila3 3.50 0 7%
Schistosoma mansoni2 1.22 2 8%
Plasmodium falciparum2 1.25 2 13%
Cryptosporidium parvum1 1.38 1 5%
Candida albicans SC53141 1.45 1 8%
Fusarium graminearum1 1.58 0 8%

Seed sequence

1362 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MSAESGPGTR LRNLPVMGDG LETSQMSTTQ AQAQPQPANA ASTNPPPPET SNPNKPKRQT
61NQLQYLLRVV LKTLWKHQFA WPFQQPVDAV KLNLPDYYKI IKTPMDMGTI KKRLENNYYW
121NAQECIQDFN TMFTNCYIYN KPGDDIVLMA EALEKLFLQK INELPTEETE IMIVQAKGRG
181RGRKETGTAK PGVSTVPNTT QASTPPQTQT PQPNPPPVQA TPHPFPAVTP DLIVQTPVMT
241VVPPQPLQTP PPVPPQPQPP PAPAPQPVQS HPPIIAATPQ PVKTKKGVKR KADTTTPTTI
301DPIHEPPSLP PEPKTTKLGQ RRESSRPVKP PKKDVPDSQQ HPAPEKSSKV SEQLKCCSGI
361LKEMFAKKHA AYAWPFYKPV DVEALGLHDY CDIIKHPMDM STIKSKLEAR EYRDAQEFGA
421DVRLMFSNCY KYNPPDHEVV AMARKLQDVF EMRFAKMPDE PEEPVVAVSS PAVPPPTKVV
481APPSSSDSSS DSSSDSDSST DDSEEERAQR LAELQEQLKA VHEQLAALSQ PQQNKPKKKE
541KDKKEKKKEK HKRKEEVEEN KKSKAKEPPP KKTKKNNSSN SNVSKKEPAP MKSKPPPTYE
601SEEEDKCKPM SYEEKRQLSL DINKLPGEKL GRVVHIIQSR EPSLKNSNPD EIEIDFETLK
661PSTLRELERY VTSCLRKKRK PQAEKVDVIA GSSKMKGFSS SESESSSESS SSDSEDSETE
721MAPKSKKKGH PGREQKKHHH HHHQQMQQAP APVPQQPPPP PQQPPPPPPP QQQQQPPPPP
781PPPSMPQQAA PAMKSSPPPF IATQVPVLEP QLPGSVFDPI GHFTQPILHL PQPELPPHLP
841QPPEHSTPPH LNQHAVVSPP ALHNALPQQP SRPSNRAAAL PPKPARPPAV SPALTQTPLL
901PQPPMAQPPQ VLLEDEEPPA PPLTSMQMQL YLQQLQKVQP PTPLLPSVKV QSQPPPPLPP
961PPHPSVQQQL QQQPPPPPPP QPQPPPQQQH QPPPRPVHLQ PMQFSTHIQQ PPPPQGQQPP
1021HPPPGQQPPP PQPAKPQQVI QHHHSPRHHK SDPYSTGHLR EAPSPLMIHS PQMSQFQSLT
1081HQSPPQQNVQ PKKQELRAAS VVQPQPLVVV KEEKIHSPII RSEPFSPSLR PEPPKHPESI
1141KAPVHLPQRP EMKPVDVGRP VIRPPEQNAP PPGAPDKDKQ KQEPKTPVAP KKDLKIKNMG
1201SWASLVQKHP TTPSSTAKSS SDSFEQFRRA AREKEEREKA LKAQAEHAEK EKERLRQERM
1261RSREDEDALE QARRAHEEAR RRQEQQQQQR QEQQQQQQQQ AAAVAAAATP QAQSSQPQSM
1321LDQQRELARK REQERRRREA MAATIDMNFQ SDLLSIFEEN LF

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 Differential Water Networks Guide Selectivity Optimization of a Cell Active BPTF Inhibitor in Neuroblastoma. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.4580510
2026 BET Bromodomain Targeting by NSAIDs: Structural, Biophysical, and Computational Insights. Proteins doi:10.1002/prot.70154
2026 Structural Basis for BD1-Preferring 2,4-Disubstituted Pyrimidine BRDT Inhibitors. J.Med.Chem. doi:10.1021/acs.jmedchem.6c00180
2026 Stabilizing Plasmodium falciparum proteins for small molecule drug discovery. Protein Sci. doi:10.1002/pro.70614
2026 The effect of peptide size on target affinity in mRNA display-derived macrocyclic peptides. Chem.Commun.(Camb.) doi:10.1039/d5cc06167a
2026 Structural insights into histone mimicry by the small hepatitis delta antigen. J.Biol.Chem. doi:10.1016/j.jbc.2026.113252
2026 Discovery and Structural Optimization of BRD4-Selective Monovalent Direct Degraders. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.6c00022
2026 Cell type-selective targeting by heterobifunctional protein binders via in-cell enrichment. Nat Commun doi:10.1038/s41467-026-77460-w
2026 Structural mechanism of diacetylated histone H2A recognition by Bromodomain-containing protein 4 in Regulation of non-homologous end-joining DNA repair. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2026.152638
2026 Fragment-Based Acs Omega doi:10.1021/acsomega.6c06516
2026 Chemical tools for BAZ2A/B biology: discovery of dual and BAZ2B-selective PROTAC degraders. Rsc Med Chem doi:10.1039/d6md00244g
2026 BRD4 binds the nucleosome via both histone and DNA interactions. Mol.Cell doi:10.1016/j.molcel.2026.07.012
2026 Charged molecular glue discovery enabled by targeted degron display. Nat.Chem.Biol. doi:10.1038/s41589-026-02182-5
2026 BRD9 recognizes lactate-induced H3K18 lactylation to drive oncogenic chromatin remodeling in hepatocellular carcinoma. Cell Death Differ. doi:10.1038/s41418-026-01698-6
2026 Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4. Nat Commun doi:10.1038/s41467-026-69565-z
2025 Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential. Adv Sci doi:10.1002/advs.202404260
2025 Binding-Site Purification of Actives (B-SPA) Enables Efficient Large-Scale Progression of Fragment Hits by Combining Multi-Step Array Synthesis With HT Crystallography. Angew.Chem.Int.Ed.Engl. doi:10.1002/anie.202424373
2025 Structure-Based Rational Design and Evaluation of BET-Aurora Kinase Dual-Inhibitors for Treatment of Cancers. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01933
2025 Structure-Guided Design of ISOX-DUAL-Based Degraders Targeting BRD4 and CBP/EP300: A Case of Degrader Collapse. J.Med.Chem. doi:10.1021/acs.jmedchem.5c00395
2025 Structure-activity relationships can be directly extracted from high-throughput crystallographic evaluation of fragment elaborations in crude reaction mixtures. Chem Sci doi:10.1039/d5sc04919a
2025 Macrocyclic dihydropyridine analogs as pan-BET BD2-preferred inhibitors. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2025.117504
2025 A bottom-up approach to find lead compounds in expansive chemical spaces. Commun Chem doi:10.1038/s42004-025-01610-2
2025 Discovery of 5-imidazole-3-methylbenz[d]isoxazole derivatives as potent and selective CBP/p300 bromodomain inhibitors for the treatment of acute myeloid leukemia. Acta Pharmacol.Sin. doi:10.1038/s41401-025-01478-x
2025 A Novel Inhibitor against the Bromodomain Protein 1 of the Malaria Pathogen Plasmodium Falciparum. Chemmedchem doi:10.1002/cmdc.202500024
2025 Multi-Water Bridges Enable Design of BET BD1-Selective Inhibitors for Pancreatic Cancer Therapy. J.Med.Chem. doi:10.1021/acs.jmedchem.4c03069
2025 Polybromo-1 Bromodomain Inhibitor Selectivity Is Mediated by a Unique Ligand-Binding Pocket Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.5c00352
2025 Key imidazolyl groups that induce phenylalanine flipping enhance the efficacy of oral BRD9 inhibitors for AML treatment. Acta Pharm Sin B doi:10.1016/j.apsb.2025.08.006
2025 Positional isomers of Indolyl-benzodiazepines display dissimilar binding and recruitment of BET transcriptional regulators to targeted genomic loci. Bioorg.Chem. doi:10.1016/j.bioorg.2025.108813
2025 A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death. Biorxiv doi:10.1101/2025.03.14.643404
2025 Enzyme-Activated Sugar-Coated Bifunctional Degraders. J.Am.Chem.Soc. doi:10.1021/jacs.5c09843
2025 Design of PROTACs utilizing the E3 ligase GID4 for targeted protein degradation. Nat.Struct.Mol.Biol. doi:10.1038/s41594-025-01537-1
2025 Structural basis for DCAF2 as a novel E3 ligase for PROTAC-mediated targeted protein degradation. Structure doi:10.1016/j.str.2025.09.006
2025 Structure of the transcriptional co-activator SAGA complex, including the histone acetyltransferase module. Mol.Cell doi:10.1016/j.molcel.2025.10.025
2024 Discovery of a potent, orally available furopyridine derivative as a novel selective bromodomain and extra-terminal domain (BET)-first bromodomain (BD1) inhibitor. Bioorg.Med.Chem.Lett. doi:10.1016/j.bmcl.2024.129848
2024 Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization. Acs Chem.Biol. doi:10.1021/acschembio.3c00427
2024 High resolution crystal structure of BRD4-BD1 in complex with a novel inhibitor precursor. Biochem.Biophys.Res.Commun. doi:10.1016/j.bbrc.2023.149284
2024 Probing Protein-Ligand Methyl-pi Interaction Geometries through Chemical Shift Measurements of Selectively Labeled Methyl Groups. J Med Chem doi:10.1039/b508541a
2024 Enhanced cellular death in liver and breast cancer cells by dual BET/BRPF1 inhibitors. Protein Sci. doi:10.1002/pro.5191
2024 Probing Protein-Ligand Methyl-pi Interaction Geometries through Chemical Shift Measurements of Selectively Labeled Methyl Groups. J.Med.Chem. doi:10.1021/acs.jmedchem.4c01128
2024 Discovery of (R)-4-(8-methoxy-2-methyl-1-(1-phenylethy)-1H-imidazo[4,5-c]quinnolin-7-yl)-3,5-dimethylisoxazole as a potent and selective BET inhibitor for treatment of acute myeloid leukemia (AML) guided by FEP calculation. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2023.115924