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2690  structures 1579  species 0  interactions 58385  sequences 1111  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 detail.[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. S2CID 29706103.
  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. S2CID 27726226.
  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. S2CID 1210925.
  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. PMC 7354103. 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 are highly conserved alpha-helical motifs that can specifically interact with acetylated lysine residues on histone tails [ PUBMED:9175470 , PUBMED:26472704 ]. 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.

This domain is present in proteins involved in a wide range of functions such as acetylating histones, remodeling chromatin, and recruiting other factors necessary for transcription, thus playing a critical role in the regulation of transcription [ PUBMED:24704920 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Prosite
Previous IDs: bromodomain;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 43
Number in full: 58385
Average length of the domain: 84.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 9.53 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -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: 28
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Species distribution

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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 2690 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2JTM7 View 3D Structure Click here
A0A0G2JZU7 View 3D Structure Click here
A0A0G2K175 View 3D Structure Click here
A0A0K3AWB8 View 3D Structure Click here
A0A0N7KJQ5 View 3D Structure Click here
A0A0P0VXC7 View 3D Structure Click here
A0A0P0X662 View 3D Structure Click here
A0A0R0EVS6 View 3D Structure Click here
A0A0R0F105 View 3D Structure Click here
A0A0R0F5T5 View 3D Structure Click here
A0A0R0F849 View 3D Structure Click here
A0A0R0FAE3 View 3D Structure Click here
A0A0R0FEY3 View 3D Structure Click here
A0A0R0FU46 View 3D Structure Click here
A0A0R0GAG4 View 3D Structure Click here
A0A0R0GF96 View 3D Structure Click here
A0A0R0HW01 View 3D Structure Click here
A0A0R0I9Z0 View 3D Structure Click here
A0A0R0JUQ7 View 3D Structure Click here
A0A0R4IBT4 View 3D Structure Click here
A0A0R4IJ25 View 3D Structure Click here
A0A0R4IPF2 View 3D Structure Click here
A0A0R4IS80 View 3D Structure Click here
A0A0R4IUG1 View 3D Structure Click here
A0A0R4IVN8 View 3D Structure Click here
A0A0R4IXF6 View 3D Structure Click here
A0A0R4IY90 View 3D Structure Click here
A0A178W3E8 View 3D Structure Click here
A0A1D6EHJ1 View 3D Structure Click here
A0A1D6EUH1 View 3D Structure Click here
A0A1D6EWT6 View 3D Structure Click here
A0A1D6EYC4 View 3D Structure Click here
A0A1D6F4G5 View 3D Structure Click here
A0A1D6FEL1 View 3D Structure Click here
A0A1D6FFQ3 View 3D Structure Click here
A0A1D6GQK6 View 3D Structure Click here
A0A1D6H5K1 View 3D Structure Click here
A0A1D6HCG5 View 3D Structure Click here
A0A1D6I782 View 3D Structure Click here
A0A1D6IAY5 View 3D Structure Click here