3pxe

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref>
[https://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN] E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8.<ref>PMID:10500182</ref> <ref>PMID:10724175</ref> <ref>PMID:11836499</ref> <ref>PMID:12890688</ref> <ref>PMID:12887909</ref> <ref>PMID:14976165</ref> <ref>PMID:14990569</ref> <ref>PMID:16818604</ref> <ref>PMID:16326698</ref> <ref>PMID:18056443</ref> <ref>PMID:17525340</ref> <ref>PMID:19261748</ref> <ref>PMID:19369211</ref> <ref>PMID:20351172</ref> <ref>PMID:20364141</ref>
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== Publication Abstract from PubMed ==
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The BRCA1 BRCT domain binds pSer-x-x-Phe motifs in partner proteins to regulate the cellular response to DNA damage. Approximately 120 distinct missense variants have been identified in the BRCA1 BRCT through breast cancer screening, and several of these have been linked to an in-creased cancer risk. Here we probe the structures and peptide-binding activities of variants that affect the BRCA1 BRCT phospho-peptide-binding groove. The results obtained from the G1656D and T1700A variants illustrate the role of Ser1655 in pSer recognition. Mutations at Arg1699 (R1699W and R1699Q) significantly reduce peptide binding, through loss of contacts to the main chain of the Phe (+3) residue, and, in the case of R1699W, to a destabilization of the BRCT fold. The R1835P and E1836K variants do not dramatically reduce peptide binding, in spite of the fact that these mutations sig-nificantly alter the structure of the walls of the Phe (+3) pocket.
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Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition.,Coquelle N, Green R, Glover JN Biochemistry. 2011 Apr 7. PMID:21473589<ref>PMID:21473589</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3pxe" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==

Current revision

Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: E1836K

PDB ID 3pxe

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