4k6j

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==Human cohesin inhibitor WapL==
==Human cohesin inhibitor WapL==
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<StructureSection load='4k6j' size='340' side='right' caption='[[4k6j]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
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<StructureSection load='4k6j' size='340' side='right'caption='[[4k6j]], [[Resolution|resolution]] 2.62&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4k6j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K6J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K6J FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4k6j]] 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=4K6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K6J FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6205&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WAPAL, FOE, KIAA0261, WAPL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k6j OCA], [http://pdbe.org/4k6j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k6j RCSB], [http://www.ebi.ac.uk/pdbsum/4k6j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k6j ProSAT]</span></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=4k6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k6j OCA], [https://pdbe.org/4k6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k6j RCSB], [https://www.ebi.ac.uk/pdbsum/4k6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k6j ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/WAPL_HUMAN WAPL_HUMAN]] Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin. Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair.<ref>PMID:15150110</ref> <ref>PMID:17113138</ref> <ref>PMID:17112726</ref> <ref>PMID:19696148</ref> <ref>PMID:19907496</ref> <ref>PMID:21111234</ref>
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[https://www.uniprot.org/uniprot/WAPL_HUMAN WAPL_HUMAN] Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin. Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair.<ref>PMID:15150110</ref> <ref>PMID:17113138</ref> <ref>PMID:17112726</ref> <ref>PMID:19696148</ref> <ref>PMID:19907496</ref> <ref>PMID:21111234</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Cohesin, along with positive regulators, establishes sister-chromatid cohesion by forming a ring to circle chromatin. The wings apart-like protein (Wapl) is a key negative regulator of cohesin and forms a complex with precocious dissociation of sisters protein 5 (Pds5) to promote cohesin release from chromatin. Here we report the crystal structure and functional characterization of human Wapl. Wapl contains a flexible, variable N-terminal region (Wapl-N) and a conserved C-terminal domain (Wapl-C) consisting of eight HEAT (Huntingtin, Elongation factor 3, A subunit, and target of rapamycin) repeats. Wapl-C folds into an elongated structure with two lobes. Structure-based mutagenesis maps the functional surface of Wapl-C to two distinct patches (I and II) on the N lobe and a localized patch (III) on the C lobe. Mutating critical patch I residues weaken Wapl binding to cohesin and diminish sister-chromatid resolution and cohesin release from mitotic chromosomes in human cells and Xenopus egg extracts. Surprisingly, patch III on the C lobe does not contribute to Wapl binding to cohesin or its known regulators. Although patch I mutations reduce Wapl binding to intact cohesin, they do not affect Wapl-Pds5 binding to the cohesin subcomplex of sister chromatid cohesion protein 1 (Scc1) and stromal antigen 2 (SA2) in vitro, which is instead mediated by Wapl-N. Thus, Wapl-N forms extensive interactions with Pds5 and Scc1-SA2. Wapl-C interacts with other cohesin subunits and possibly unknown effectors to trigger cohesin release from chromatin.
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Structure of the human cohesin inhibitor Wapl.,Ouyang Z, Zheng G, Song J, Borek DM, Otwinowski Z, Brautigam CA, Tomchick DR, Rankin S, Yu H Proc Natl Acad Sci U S A. 2013 Jun 17. PMID:23776203<ref>PMID:23776203</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 4k6j" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Ouyang, Z]]
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[[Category: Large Structures]]
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[[Category: Tomchick, D R]]
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[[Category: Ouyang Z]]
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[[Category: Yu, H]]
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[[Category: Tomchick DR]]
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[[Category: Cell adhesion inhibitor]]
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[[Category: Yu H]]
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[[Category: Cell cycle]]
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[[Category: Cohesin regulator]]
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[[Category: Heat repeat]]
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[[Category: Nuclear protein]]
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[[Category: Protein-binding]]
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Current revision

Human cohesin inhibitor WapL

PDB ID 4k6j

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