3zvy

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[[Image:3zvy.jpg|left|200px]]
 
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==PHD finger of human UHRF1 in complex with unmodified histone H3 N- terminal tail==
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The line below this paragraph, containing "STRUCTURE_3zvy", creates the "Structure Box" on the page.
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<StructureSection load='3zvy' size='340' side='right'caption='[[3zvy]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3zvy]] is a 4 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=3ZVY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZVY FirstGlance]. <br>
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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]] 1.95&#8491;</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3zvy| PDB=3zvy | SCENE= }}
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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=3zvy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zvy OCA], [https://pdbe.org/3zvy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zvy RCSB], [https://www.ebi.ac.uk/pdbsum/3zvy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zvy ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN] Note=Defects in UHRF1 may be a cause of cancers. Overexpressed in many different forms of human cancers, including bladder, breast, cervical, colorectal and prostate cancers, as well as pancreatic adenocarcinomas, rhabdomyosarcomas and gliomas. Plays an important role in the correlation of histone modification and gene silencing in cancer progression. Expression is associated with a poor prognosis in patients with various cancers, suggesting that it participates in cancer progression.
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== Function ==
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[https://www.uniprot.org/uniprot/UHRF1_HUMAN UHRF1_HUMAN] Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. May be involved in DNA repair.<ref>PMID:10646863</ref> <ref>PMID:15009091</ref> <ref>PMID:15361834</ref> <ref>PMID:17673620</ref> <ref>PMID:17967883</ref> <ref>PMID:19056828</ref> <ref>PMID:21745816</ref> <ref>PMID:22945642</ref> <ref>PMID:21777816</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human UHRF1 protein (ubiquitin-like containing PHD and RING finger domains 1) has emerged as a potential cancer target due to its implication in cell cycle regulation, maintenance of DNA methylation after replication and heterochromatin formation. UHRF1 functions as an adaptor protein that binds to histones and recruits histone modifying enzymes, like HDAC1 or G9a, which exert their action on chromatin. In this work, we show the binding specificity of the PHD finger of human UHRF1 (huUHRF1-PHD) towards unmodified histone H3 N-terminal tail using native gel electrophoresis and isothermal titration calorimetry. We report the molecular basis of this interaction by determining the crystal structure of huUHRF1-PHD in complex with the histone H3 N-terminal tail. The structure reveals a new mode of histone recognition involving an extra conserved zinc finger preceding the conventional PHD finger region. This additional zinc finger forms part of a large surface cavity that accommodates the side chain of the histone H3 lysine K4 (H3K4) regardless of its methylation state. Mutation of Q330, which specifically interacts with H3K4, to alanine has no effect on the binding, suggesting a loose interaction between huUHRF1-PHD and H3K4. On the other hand, the recognition appears to rely on histone H3R2, which fits snugly into a groove on the protein and makes tight interactions with the conserved aspartates D334 and D337. Indeed, a mutation of the former aspartate disrupts the formation of the complex, while mutating the latter decreases the binding affinity nine-fold.
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===PHD FINGER OF HUMAN UHRF1 IN COMPLEX WITH UNMODIFIED HISTONE H3 N-TERMINAL TAIL===
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The PHD Finger of Human UHRF1 Reveals a New Subgroup of Unmethylated Histone H3 Tail Readers.,Lallous N, Legrand P, McEwen AG, Ramon-Maiques S, Samama JP, Birck C PLoS One. 2011;6(11):e27599. Epub 2011 Nov 11. PMID:22096602<ref>PMID:22096602</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 3zvy" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_22096602}}, adds the Publication Abstract to the page
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 22096602 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_22096602}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[3zvy]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZVY OCA].
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==Reference==
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<ref group="xtra">PMID:022096602</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Birck, C.]]
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[[Category: Large Structures]]
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[[Category: Ewen, A G.Mc.]]
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[[Category: Birck C]]
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[[Category: Lallous, N.]]
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[[Category: Lallous N]]
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[[Category: Legrand, P.]]
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[[Category: Legrand P]]
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[[Category: Samama, J P.]]
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[[Category: Mc Ewen AG]]
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[[Category: Epigenetic]]
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[[Category: Samama JP]]
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[[Category: Histone reader]]
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[[Category: Ligase-peptide complex]]
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Current revision

PHD finger of human UHRF1 in complex with unmodified histone H3 N- terminal tail

PDB ID 3zvy

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