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==Crystal structure of PZP domain of human AF10 protein==
==Crystal structure of PZP domain of human AF10 protein==
<StructureSection load='5dag' size='340' side='right' caption='[[5dag]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
<StructureSection load='5dag' size='340' side='right'caption='[[5dag]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5dag]] is a 1 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=5DAG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DAG FirstGlance]. <br>
<table><tr><td colspan='2'>[[5dag]] is a 1 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=5DAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DAG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.6&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dah|5dah]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MLLT10, AF10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [https://pdbe.org/5dag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [https://www.ebi.ac.uk/pdbsum/5dag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dag ProSAT]</span></td></tr>
<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=5dag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dag OCA], [http://pdbe.org/5dag PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dag RCSB], [http://www.ebi.ac.uk/pdbsum/5dag PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dag ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.  A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.  
[https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Precursor T-cell acute lymphoblastic leukemia. A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with KMT2A/MLL1. The result is a rogue activator protein.  A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN]] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref> 
[https://www.uniprot.org/uniprot/AF10_HUMAN AF10_HUMAN] Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA.<ref>PMID:17868029</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
AF10, a DOT1L cofactor, is required for H3K79 methylation and cooperates with DOT1L in leukemogenesis. However, the molecular mechanism by which AF10 regulates DOT1L-mediated H3K79 methylation is not clear. Here we report that AF10 contains a "reader" domain that couples unmodified H3K27 recognition to H3K79 methylation. An AF10 region consisting of a PHD finger-Zn knuckle-PHD finger (PZP) folds into a single module that recognizes amino acids 22-27 of H3, and this interaction is abrogated by H3K27 modification. Structural studies reveal that H3 binding triggers rearrangement of the PZP module to form an H3(22-27)-accommodating channel and that the unmodified H3K27 side chain is encased in a compact hydrogen-bond acceptor-lined cage. In cells, PZP recognition of H3 is required for H3K79 dimethylation, expression of DOT1L-target genes, and proliferation of DOT1L-addicted leukemic cells. Together, our results uncover a pivotal role for H3K27-via readout by the AF10 PZP domain-in regulating the cancer-associated enzyme DOT1L.
 
The PZP Domain of AF10 Senses Unmodified H3K27 to Regulate DOT1L-Mediated Methylation of H3K79.,Chen S, Yang Z, Wilkinson AW, Deshpande AJ, Sidoli S, Krajewski K, Strahl BD, Garcia BA, Armstrong SA, Patel DJ, Gozani O Mol Cell. 2015 Oct 15;60(2):319-27. doi: 10.1016/j.molcel.2015.08.019. Epub 2015 , Oct 1. PMID:26439302<ref>PMID:26439302</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5dag" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Chen, S]]
[[Category: Large Structures]]
[[Category: Patel, D J]]
[[Category: Chen S]]
[[Category: Epigenetic]]
[[Category: Patel DJ]]
[[Category: H3k27 recognition]]
[[Category: Histone tail reader]]
[[Category: Peptide binding protein]]
[[Category: Phd finger]]
Retrieved from "https://proteopedia.org/5dag"