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2170  structures 1180  species 5  interactions 35320  sequences 836  architectures

Family: Bromodomain (PF00439)

Summary: Bromodomain

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Bromodomain Edit Wikipedia article

1e6i bromodomain.png
Ribbon diagram of the GCN5 bromodomain from Saccharomyces cerevisiae, colored from blue (N-terminus) to red (C-terminus).[1]

A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the N-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes.[2] Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine.[1][3]


The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene Brahma/brm, and showed sequence similarity to genes involved in transcriptional activation.[4] The name "bromodomain" is derived from the relationship of this domain with Brahma and is unrelated to the chemical element bromine.

Bromodomain-containing proteins

Bromodomain-containing proteins can have a wide variety of functions, ranging from histone acetyltransferase activity and chromatin remodeling to transcriptional mediation and co-activation. Of the 43 known in 2015, 11 had two bromodomains, and one protein had 6 bromodomains.[2] Preparation, biochemical analysis, and structure determination of the bromodomain containing proteins have been described in details.[5]

Bromo- and Extra-Terminal domain (BET) family

A well-known example of a bromodomain family is the BET (Bromodomain and extraterminal domain) family. Members of this family include BRD2, BRD3, BRD4 and BRDT.


However proteins such as ASH1L also contain a bromodomain. Dysfunction of BRD proteins has been linked to diseases such as human squamous cell carcinoma and other forms of cancer.[6] Histone acetyltransferases, including EP300 and PCAF, have bromodomains in addition to acetyl-transferase domains.[7][8] [9]

Not considered part of the BET family (yet containing a bromodomain) are BRD7, and BRD9.

Role in human disease

The role of bromodomains in translating a deregulated cell acetylome into disease phenotypes was recently unveiled by the development of small molecule bromodomain inhibitors. This breakthrough discovery highlighted bromodomain-containing proteins as key players in cancer biology, as well as inflammation and remyelination in multiple sclerosis.[2]

Members of the BET family have been implicated as targets in both human cancer[10][11] and multiple sclerosis.[12] BET inhibitors have shown therapeutic effects in multiple preclinical models of cancer and are currently in clinical trials in the United States.[13] Their application in multiple sclerosis is still in the preclinical stage.

Small molecule inhibitors of non-BET bromodomain proteins BRD7 and BRD9 have also been developed.[14][15]

See also


  1. ^ a b PDB: 1e6i​; Owen DJ, Ornaghi P, Yang JC, Lowe N, Evans PR, Ballario P, Neuhaus D, Filetici P, Travers AA (November 2000). "The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase gcn5p". EMBO J. 19 (22): 6141–9. doi:10.1093/emboj/19.22.6141. PMC 305837. PMID 11080160.
  2. ^ a b c Ntranos, Achilles; Casaccia, Patrizia (2016). "Bromodomains: Translating the words of lysine acetylation into myelin injury and repair". Neuroscience Letters. 625: 4–10. doi:10.1016/j.neulet.2015.10.015. PMC 4841751. PMID 26472704.
  3. ^ Zeng L, Zhou MM (February 2002). "Bromodomain: an acetyl-lysine binding domain". FEBS Lett. 513 (1): 124–8. doi:10.1016/S0014-5793(01)03309-9. PMID 11911891.
  4. ^ Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC, Kennison JA (February 1992). "brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2". Cell. 68 (3): 561–72. doi:10.1016/0092-8674(92)90191-E. PMID 1346755.
  5. ^ Ren, C; Zeng, L; Zhou, MM (2016). "Preparation, Biochemical Analysis, and Structure Determination of the Bromodomain, an Acetyl-Lysine Binding Domain". Methods in Enzymology. 573: 321–43. doi:10.1016/bs.mie.2016.01.018. ISBN 9780128053652. PMID 27372760.
  6. ^ Filippakopoulos, Panagis (2012). "Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family". Cell. 149 (1): 214–231. doi:10.1016/j.cell.2012.02.013. PMC 3326523. PMID 22464331.
  7. ^ Dhalluin, C; Carlson, J. E.; Zeng, L; He, C; Aggarwal, A. K.; Zhou, M. M.; Zhou, Ming-Ming (1999). "Structure and ligand of a histone acetyltransferase bromodomain". Nature. 399 (6735): 491–6. doi:10.1038/20974. PMID 10365964.
  8. ^ Santillan, D. A.; Theisler, C. M.; Ryan, A. S.; Popovic, R; Stuart, T; Zhou, M. M.; Alkan, S; Zeleznik-Le, N. J. (2006). "Bromodomain and histone acetyltransferase domain specificities control mixed lineage leukemia phenotype". Cancer Research. 66 (20): 10032–9. doi:10.1158/0008-5472.CAN-06-2597. PMID 17047066.
  9. ^ Hay, D. A.; Fedorov, O; Martin, S; Singleton, D. C.; Tallant, C; Wells, C; Picaud, S; Philpott, M; Monteiro, O. P.; Rogers, C. M.; Conway, S. J.; Rooney, T. P.; Tumber, A; Yapp, C; Filippakopoulos, P; Bunnage, M. E.; Müller, S; Knapp, S; Schofield, C. J.; Brennan, P. E. (2014). "Discovery and optimization of small-molecule ligands for the CBP/p300 bromodomains". Journal of the American Chemical Society. 136 (26): 9308–19. doi:10.1021/ja412434f. PMC 4183655. PMID 24946055.
  10. ^ Jung, Marie; Gelato, Kathy A; Fernández-Montalván, Amaury; Siegel, Stephan; Haendler, Bernard (2015-06-16). "Targeting BET bromodomains for cancer treatment". Epigenomics. 7 (3): 487–501. doi:10.2217/epi.14.91. PMID 26077433.
  11. ^ Da Costa, D.; Agathanggelou, A.; Perry, T.; Weston, V.; Petermann, E.; Zlatanou, A.; Oldreive, C.; Wei, W.; Stewart, G. (2013-07-19). "BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia". Blood Cancer Journal. 3 (7): e126. doi:10.1038/bcj.2013.24. PMC 3730202. PMID 23872705.
  12. ^ Gacias, Mar; Gerona-Navarro, Guillermo; Plotnikov, Alexander N.; Zhang, Guangtao; Zeng, Lei; Kaur, Jasbir; Moy, Gregory; Rusinova, Elena; Rodriguez, Yoel (2014). "Selective Chemical Modulation of Gene Transcription Favors Oligodendrocyte Lineage Progression". Chemistry & Biology. 21 (7): 841–854. doi:10.1016/j.chembiol.2014.05.009. ISSN 1074-5521. PMC 4104156. PMID 24954007.
  13. ^ Shi, Junwei (2014). "The Mechanisms behind the Therapeutic Activity of BET Bromodomain Inhibition". Molecular Cell. 54 (5): 728–736. doi:10.1016/j.molcel.2014.05.016. PMC 4236231. PMID 24905006.
  14. ^ Clark, P. G.; Vieira, L. C.; Tallant, C; Fedorov, O; Singleton, D. C.; Rogers, C. M.; Monteiro, O. P.; Bennett, J. M.; Baronio, R; Müller, S; Daniels, D. L.; Méndez, J; Knapp, S; Brennan, P. E.; Dixon, D. J. (2015). "LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor". Angewandte Chemie International Edition. 54 (21): 6217–21. doi:10.1002/anie.201501394. PMC 4449114. PMID 25864491.
  15. ^ Theodoulou, N. H.; Bamborough, P; Bannister, A. J.; Becher, I; Bit, R. A.; Che, K. H.; Chung, C. W.; Dittmann, A; Drewes, G; Drewry, D. H.; Gordon, L; Grandi, P; Leveridge, M; Lindon, M; Michon, A. M.; Molnar, J; Robson, S. C.; Tomkinson, N. C.; Kouzarides, T; Prinjha, R. K.; Humphreys, P. G. (2015). "The Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition". Journal of Medicinal Chemistry. 59 (4): 1425–39. doi:10.1021/acs.jmedchem.5b00256. PMID 25856009.

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Bromodomain Provide feedback

Bromodomains are 110 amino acid long domains, that are found in many chromatin associated proteins. Bromodomains can interact specifically with acetylated lysine [3].

Literature references

  1. Haynes SR, Dollard C, Winston F, Beck S, Trowsdale J, Dawid IB; , Nucleic Acids Res 1992;20:2603-2603.: The bromodomain: a conserved sequence found in human, Drosophila and yeast proteins. PUBMED:1350857 EPMC:1350857

  2. Jeanmougin F, Wurtz J-M, Le Douarin B, Chambon P, Losson R; , Trends Biochem Sci 1997;22:151-153.: The bromodomain revisited. PUBMED:9175470 EPMC:9175470

  3. Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM; , Nature 1999;399:491-496.: Structure and ligand of a histone acetyltransferase bromodomain. PUBMED:10365964 EPMC:10365964

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001487

Bromodomains are found in a variety of mammalian, invertebrate and yeast DNA-binding proteins [PUBMED:1350857]. Bromodomains can interact with acetylated lysine [PUBMED:9175470]. In some proteins, the classical bromodomain has diverged to such an extent that parts of the region are either missing or contain an insertion (e.g., mammalian protein HRX, Caenorhabditis elegans hypothetical protein ZK783.4, yeast protein YTA7). The bromodomain may occur as a single copy, or in duplicate.

The precise function of the domain is unclear, but it may be involved in protein-protein interactions and may play a role in assembly or activity of multi-component complexes involved in transcriptional activation [PUBMED:7580139].

Gene Ontology

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Domain organisation

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Seed source: Prosite
Previous IDs: bromodomain;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 44
Number in full: 35320
Average length of the domain: 84.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 9.97 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.7 21.7
Trusted cut-off 21.7 21.7
Noise cut-off 21.6 21.6
Model length: 84
Family (HMM) version: 26
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There are 5 interactions for this family. More...

Bromodomain ASF1_hist_chap PHD DUF902 PHD


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Bromodomain domain has been found. There are 2170 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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