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493  structures 705  species 5  interactions 13699  sequences 521  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]
Symbol Bromodomain
Pfam PF00439
InterPro IPR001487
SCOP 1b91
CDD cd04369

A bromodomain is an approximately 110 amino acid protein domain that recognizes monoacetylated lysine residues such as those on the N-terminal tails of histones. 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][2]


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.[3] The name "bromodomain" is derived from the relationship of this domain with Brahma and is unrelated to the chemical element bromine.


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.[4]

Several histone acetyltransferases, including KMT2A, EP300, and PCAF, have bromodomains in addition to acetyl-transferase domains.[5][6][7]

Small molecule inhibition

Members of the BET family have been implicated as targets in human cancer. These BET inhibitors have shown therapeutic effects in multiple preclinical models of cancer and are currently in clinical trials in the United States.[8]

Small molecule inhibitors of non-BET bromodomain proteins BRD7 and BRD9 have also been developed.[9][10]

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. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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.  edit
  6. ^ 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.  edit
  7. ^ 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.  edit
  8. ^ 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. 
  9. ^ 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: n/a. doi:10.1002/anie.201501394. PMID 25864491.  edit
  10. ^ 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: 150430080108003. doi:10.1021/acs.jmedchem.5b00256. PMID 25856009.  edit

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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

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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Curation and family details

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Seed source: Prosite
Previous IDs: bromodomain;
Type: Domain
Author: Finn RD
Number in seed: 49
Number in full: 13699
Average length of the domain: 84.20 aa
Average identity of full alignment: 26 %
Average coverage of the sequence by the domain: 10.42 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 84
Family (HMM) version: 21
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Species distribution

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There are 5 interactions for this family. More...

PHD ASF1_hist_chap PHD DUF902 Bromodomain


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 493 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 seqence.

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