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|  BROMO Domain |
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| Structure:
 A single bromodomain structure is available from HAT coactivator P/CAF (p300/CBP associated factor). The structure is an unusual left-handed up-and-down four helix bundle with a left handed twist. A hydrophobic pocket in the bromodomain creates a binding site for the acetylated moiety. Intermolecular interactions are primarily hydrophobic.
Structure Reference:
Owen, DJ. et al. (2000) EMBO J. 19(22): 6141-9. PDB: 1E6I.
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| Domain binding and function:
Identified in over one hundred proteins from yeast to man, the approximately 110 amino acid bromodomain can bind to acetylated lysine residues. Acetylation of lysine is a post-translational modification that is particularly notable in the flexible N- and C-terminal tails of histones and, along with methylation of lysines and phosphorylation of serine and threonine residues, is important for coupling histones to changes in chromatin organization and for the epigenetic control of gene expression. The bromodomain is generally found in proteins that regulate chromatin structure and gene expression such as histone acetyltransferases and the ATPase component of certain nucleosomes-remodeling complexes. The mode of recognition of acetyl-lysine by the Bromo domain is similar to that of acetyl-CoA by histone acetyltransferases, though the bromodomain is the only domain known to interact with acetylated lysine containing peptides. Recognition of acetyl-lysine by bromodomain proteins is not limited to histones. This is illustrated by the bromodomain of CREB binding protein transcriptional coactivator (CBP) that recognizes lysine-acetylated p53 at acetyl-lysine 382. The interaction between the bromodomain and acetyl-p53 is triggered upon DNA damage to promote p53-induced transcriptional activation of the CDK inhibitor p21 and cell cycle arrest.
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| Examples of Proteins:
| BROMO domain protein |
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Binding partner | Specific Binding motif
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| P/CAF |
| Tat
| BSYGRKAcKRRQRC
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CBP (CREB Binding Protein)
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Ternary complex factor Elk-1
| Not known
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| SSPQPKKAcKPLDGE
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P53
| SHLKSKKAcGQSTSRHKK
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| SSPQPKKAcKPLDGE
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Gcn5p
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Histone H4
| AKAcRHR
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Celtix-1
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IRF-2
| Hyperacetylated form of IRF-2
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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