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| | <StructureSection load='3c5r' size='340' side='right'caption='[[3c5r]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3c5r' size='340' side='right'caption='[[3c5r]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3c5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C5R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3c5r]] is a 2 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=3C5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C5R FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BARD1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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=3c5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c5r OCA], [https://pdbe.org/3c5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c5r RCSB], [https://www.ebi.ac.uk/pdbsum/3c5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c5r ProSAT]</span></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=3c5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c5r OCA], [https://pdbe.org/3c5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c5r RCSB], [https://www.ebi.ac.uk/pdbsum/3c5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c5r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/BARD1_HUMAN BARD1_HUMAN]] Probable E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.<ref>PMID:10477523</ref> <ref>PMID:12890688</ref> <ref>PMID:14976165</ref> <ref>PMID:20351172</ref>
| + | [https://www.uniprot.org/uniprot/BARD1_HUMAN BARD1_HUMAN] Probable E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.<ref>PMID:10477523</ref> <ref>PMID:12890688</ref> <ref>PMID:14976165</ref> <ref>PMID:20351172</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: III, D Fox]] | + | [[Category: Fox III D]] |
| - | [[Category: Klevit, R E]] | + | [[Category: Klevit RE]] |
| - | [[Category: Stenkamp, R E]]
| + | [[Category: Le Trong I]] |
| - | [[Category: Trong, I Le]] | + | [[Category: Stenkamp RE]] |
| - | [[Category: Ank repeat]] | + | |
| - | [[Category: Ankyrin repeat]]
| + | |
| - | [[Category: Bard1]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Extended loop]]
| + | |
| - | [[Category: Four repeat]]
| + | |
| - | [[Category: Helix]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
BARD1_HUMAN Probable E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BARD1 is the constitutive nuclear partner to the breast and ovarian cancer-specific tumor suppressor BRCA1. Together, they form a heterodimeric complex responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. We report the 2.0A structure of the BARD1 ankyrin repeat domain. The structure includes four ankyrin repeats with a non-canonical C-terminal capping ankyrin repeat and a well ordered extended loop preceding the first repeat. Conserved surface features show an acidic patch and an acidic pocket along the surface typically used by ankyrin repeat domains for binding cognate proteins. We also demonstrate that two reported mutations, N470S and V507M, in the ankyrin repeat domain do not result in observable structural defects. These results provide a structural basis for exploring the biological function of the ankyrin repeat domain and for modeling BARD1 isoforms.
Crystal structure of the BARD1 ankyrin repeat domain and its functional consequences.,Fox D 3rd, Le Trong I, Rajagopal P, Brzovic PS, Stenkamp RE, Klevit RE J Biol Chem. 2008 Jul 25;283(30):21179-86. Epub 2008 May 14. PMID:18480049[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kleiman FE, Manley JL. Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. Science. 1999 Sep 3;285(5433):1576-9. PMID:10477523
- ↑ Wu-Baer F, Lagrazon K, Yuan W, Baer R. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. J Biol Chem. 2003 Sep 12;278(37):34743-6. Epub 2003 Jul 30. PMID:12890688 doi:10.1074/jbc.C300249200
- ↑ Morris JR, Solomon E. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. Hum Mol Genet. 2004 Apr 15;13(8):807-17. Epub 2004 Feb 19. PMID:14976165 doi:10.1093/hmg/ddh095
- ↑ Wu-Baer F, Ludwig T, Baer R. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. Mol Cell Biol. 2010 Jun;30(11):2787-98. doi: 10.1128/MCB.01056-09. Epub 2010 Mar , 29. PMID:20351172 doi:10.1128/MCB.01056-09
- ↑ Fox D 3rd, Le Trong I, Rajagopal P, Brzovic PS, Stenkamp RE, Klevit RE. Crystal structure of the BARD1 ankyrin repeat domain and its functional consequences. J Biol Chem. 2008 Jul 25;283(30):21179-86. Epub 2008 May 14. PMID:18480049 doi:10.1074/jbc.M802333200
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