 BRCT Domain | |
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| Class:Phospho-Ser binding | |
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Structure:
The BRCT domain consists of repeats containing approximately ~90-100 amino acids. Each BRCT repeat adopts a characteristic fold with a central, parallel four-stranded β-sheet, along with a pair of α-helices packed against one face and a single α-helix packed against the opposite face of the sheet. The arrangement of the α1, α3 and the central β-sheet is conserved in all repeats as a number of key hydrophobic residues maintain the packing of the BRCT fold. The two BRCT repeats in BRCA1 interact in a head-to-tail manner. In this arrangement, the N-terminal half of the one BRCT domain forms a pocket for pSer as the C-terminal half of the same domain generates a hydrophobic pocket for Phe.
Structure Reference:Shiozaki, E. N. et al. (2004) Mol. Cell. 14(3), 405-412. PDB: 1T29.Clapperton, J.A. et al. (2004) Nature Struct. Biol. 11(6), 512-518. SWilliams, R. S. et al. (2004) Nature Struct. Biol. 11(6), 519-525. | |
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Domain binding and function:
The BRCT (BRCA1 C-terminal) domain was first identified by sequence analysis of the C-terminus of the BRCA1 gene which contained a pair of repeats found mutated by truncation or loss in cancers, indicating its function to be essential for the tumor suppressor function of BRCA1. The BRCT domain consists of ~90-100 amino acid residues arranged into a central β-sheet surrounded by 2-3 α-helices. While single BRCT repeats have been found (e.g. XRCC1 and DNA ligase III), most BRCT repeats that have been detected occur in multiples. Functionally, BRCT containing proteins are involved in DNA repair, the DNA damage response and cell cycle regulation, most importantly by directing protein-protein interactions. In a number of cases, tandem BRCT repeats constitute a phosphopeptide binding domain with ligand specificity encoded in residues C-terminal to the critical phospho-serine. Phosphopeptide binding occurs in a groove that involves both the N- and C-terminal repeats and exhibits specificity for phospho-serine containing peptides.
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Examples of Proteins:
| BRCT domain protein |
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Binding partners |
Phosphopeptide ligands |
| BRCA1 |  |
BACH1, p53, CtIP, HDACs, CBP |
pSer-X-X-Phe |
XRCC1
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LigIIIα
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| XRCC4 | |
DNA Ligase IV |
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| TOPBP1 | |
E2F1 |
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| 53BP1 | |
p53 |
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| RAD9 | |
RAD4 |
pSer-[YILQP]-I-I |
| BARD | |
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pSer-[DE]-[DE]-E |
| MDC1/NFBD1 | |
H2AX
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Ser-Ω-[EVDI]-Ω |
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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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