View source for 8rs8


==Crystal structure of BRCA1 BRCTs in complex with a RIF1 phosphopeptide==
<StructureSection load='8rs8' size='340' side='right'caption='[[8rs8]], [[Resolution|resolution]] 1.31&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8rs8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8RS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RS8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.31&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8rs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rs8 OCA], [https://pdbe.org/8rs8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rs8 RCSB], [https://www.ebi.ac.uk/pdbsum/8rs8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rs8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BRCA1_HUMAN BRCA1_HUMAN] Defects in BRCA1 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.<ref>PMID:11301010</ref> <ref>PMID:15133502</ref> <ref>PMID:7545954</ref> <ref>PMID:12427738</ref> <ref>PMID:18285836</ref> <ref>PMID:7939630</ref> <ref>PMID:7894491</ref> <ref>PMID:7894493</ref> <ref>PMID:8554067</ref> <ref>PMID:8776600</ref> <ref>PMID:8723683</ref> <ref>PMID:9760198</ref> <ref>PMID:9482581</ref> <ref>PMID:9609997</ref> <ref>PMID:10323242</ref> <ref>PMID:12442275</ref> <ref>PMID:12938098</ref> <ref>PMID:14722926</ref>   Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:[https://omim.org/entry/604370 604370]. A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. Note=Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.  Defects in BRCA1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease.  Defects in BRCA1 are a cause of susceptibility to pancreatic cancer type 4 (PNCA4) [MIM:[https://omim.org/entry/614320 614320]. A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue.
== 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> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Day M]]
[[Category: Oliver AW]]
[[Category: Pearl LH]]