7liq

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==X-ray structure of SPOP MATH domain (S119A)==
==X-ray structure of SPOP MATH domain (S119A)==
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<StructureSection load='7liq' size='340' side='right'caption='[[7liq]]' scene=''>
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<StructureSection load='7liq' size='340' side='right'caption='[[7liq]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LIQ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[7liq]] is a 1 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=7LIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LIQ FirstGlance]. <br>
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</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=7liq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7liq OCA], [https://pdbe.org/7liq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7liq RCSB], [https://www.ebi.ac.uk/pdbsum/7liq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7liq ProSAT]</span></td></tr>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPOP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7liq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7liq OCA], [https://pdbe.org/7liq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7liq RCSB], [https://www.ebi.ac.uk/pdbsum/7liq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7liq ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[[https://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN]] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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53BP1 activates nonhomologous end joining (NHEJ) and inhibits homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Dissociation of 53BP1 from DSBs and consequent activation of HR, a less error-prone pathway than NHEJ, helps maintain genome integrity during DNA replication; however, the underlying mechanisms are not fully understood. Here, we demonstrate that E3 ubiquitin ligase SPOP promotes HR during S phase of the cell cycle by excluding 53BP1 from DSBs. In response to DNA damage, ATM kinase-catalyzed phosphorylation of SPOP causes a conformational change in SPOP, revealed by x-ray crystal structures, that stabilizes its interaction with 53BP1. 53BP1-bound SPOP induces polyubiquitination of 53BP1, eliciting 53BP1 extraction from chromatin by a valosin-containing protein/p97 segregase complex. Our work shows that SPOP facilitates HR repair over NHEJ during DNA replication by contributing to 53BP1 removal from chromatin. Cancer-derived SPOP mutations block SPOP interaction with 53BP1, inducing HR defects and chromosomal instability.
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ATM-phosphorylated SPOP contributes to 53BP1 exclusion from chromatin during DNA replication.,Wang D, Ma J, Botuyan MV, Cui G, Yan Y, Ding D, Zhou Y, Krueger EW, Pei J, Wu X, Wang L, Pei H, McNiven MA, Ye D, Mer G, Huang H Sci Adv. 2021 Jun 18;7(25). pii: 7/25/eabd9208. doi: 10.1126/sciadv.abd9208., Print 2021 Jun. PMID:34144977<ref>PMID:34144977</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 7liq" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Botuyan MV]]
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[[Category: Botuyan, M V]]
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[[Category: Cui G]]
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[[Category: Cui, G]]
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[[Category: Mer G]]
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[[Category: Mer, G]]
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[[Category: Dna damage response]]
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[[Category: Homologous recombination]]
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[[Category: Protein binding]]
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[[Category: Spop]]
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[[Category: Ubiquitin ligase]]

Revision as of 03:50, 2 July 2021

X-ray structure of SPOP MATH domain (S119A)

PDB ID 7liq

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