View source for 3f8j


==Mouse UHRF1 SRA domain bound with hemi-methylated CpG, crystal structure in space group C222(1)==
<StructureSection load='3f8j' size='340' side='right'caption='[[3f8j]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3f8j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F8J FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zo0|2zo0]], [[2zo1|2zo1]], [[2zo2|2zo2]], [[3f8i|3f8i]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Uhrf1, Np95 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3f8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f8j OCA], [https://pdbe.org/3f8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f8j RCSB], [https://www.ebi.ac.uk/pdbsum/3f8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f8j ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/UHRF1_MOUSE UHRF1_MOUSE]] 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:12084726</ref> <ref>PMID:12058012</ref> <ref>PMID:14993289</ref> <ref>PMID:15361834</ref> <ref>PMID:17994007</ref> <ref>PMID:17673620</ref> <ref>PMID:21489993</ref> <ref>PMID:21268065</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f8/3f8j_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3f8j ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cytosine methylation in DNA is a major epigenetic signal, and plays a central role in propagating chromatin status during cell division. However the mechanistic links between DNA methylation and histone methylation are poorly understood. A multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is required for DNA CpG maintenance methylation at replication forks, and mouse UHRF1-null cells show enhanced susceptibility to DNA replication arrest and DNA damaging agents. Recent data demonstrated that the SET and RING associated (SRA) domain of UHRF1 binds hemimethylated CpG and flips 5-methylcytosine out of the DNA helix, whereas its tandom tudor domain and PHD domain bind the tail of histone H3 in a highly methylation sensitive manner. We hypothesize that UHRF1 brings the two components (histones and DNA) carrying appropriate markers (on the tails of H3 and hemimethylated CpG sites) ready to be assembled into a nucleosome after replication.

UHRF1, a modular multi-domain protein, regulates replication-coupled crosstalk between DNA methylation and histone modifications.,Hashimoto H, Horton JR, Zhang X, Cheng X Epigenetics. 2009 Jan 10;4(1). PMID:19077538<ref>PMID:19077538</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3f8j" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Cheng, X]]
[[Category: Hashimoto, H]]
[[Category: Horton, J R]]
[[Category: Zhang, X]]
[[Category: 5-methylcytosine]]
[[Category: Base flipping]]
[[Category: Cell cycle]]
[[Category: Cpg methylation]]
[[Category: Developmental protein]]
[[Category: Dna damage]]
[[Category: Dna repair]]
[[Category: Dna-binding]]
[[Category: Ligase]]
[[Category: Ligase-dna complex]]
[[Category: Metal-binding]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Sra]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Ubl conjugation pathway]]
[[Category: Uhrf1]]
[[Category: Zinc-finger]]