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==PHD6 domain of MLL3 in complex with histone H4==
==PHD6 domain of MLL3 in complex with histone H4==
<StructureSection load='6mlc' size='340' side='right' caption='[[6mlc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='6mlc' size='340' side='right'caption='[[6mlc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6mlc]] is a 6 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=6MLC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MLC FirstGlance]. <br>
<table><tr><td colspan='2'>[[6mlc]] is a 6 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=6MLC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MLC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <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]] 1.8&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KMT2C, HALR, KIAA1506, MLL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></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=6mlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mlc OCA], [https://pdbe.org/6mlc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mlc RCSB], [https://www.ebi.ac.uk/pdbsum/6mlc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mlc 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=6mlc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mlc OCA], [http://pdbe.org/6mlc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mlc RCSB], [http://www.ebi.ac.uk/pdbsum/6mlc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mlc ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/KMT2C_HUMAN KMT2C_HUMAN]] Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder.<ref>PMID:17500065</ref>
[https://www.uniprot.org/uniprot/KMT2C_HUMAN KMT2C_HUMAN] Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder.<ref>PMID:17500065</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MLL3 and MLL4 are two closely related members of the SET1/MLL family of histone H3K4 methyltransferases and are responsible for monomethylating histone H3K4 on enhancers, which are essential in regulating cell-type-specific gene expression. Mutations of MLL3 or MLL4 have been reported in different types of cancer. Recently, the PHD domains of MLL3/4 have been reported to recruit the MLL3/4 complexes to their target genes by binding to histone H4 during the NT2/D1 stem cell differentiation. Here we show that an extended PHD domain (ePHD6) involving the sixth PHD domain and its preceding zinc finger in MLL3 and MLL4 specifically recognizes an H4H18-containing histone H4 fragment and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4. Our in vitro methyltransferase assays and cellular experiments further reveal that the interaction between ePHD6 of MLL3/4 and histone H4 is required for their nucleosomal methylation activity and MLL4-mediated neuronal differentiation of NT2/D1 cells.


Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4.,Liu Y, Qin S, Chen TY, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG, Min J Nat Commun. 2019 Jan 3;10(1):36. doi: 10.1038/s41467-018-07906-3. PMID:30604749<ref>PMID:30604749</ref>
==See Also==
 
*[[Histone 3D structures|Histone 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
</div>
<div class="pdbe-citations 6mlc" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Histone-lysine N-methyltransferase]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Arrowsmith, C H]]
[[Category: Arrowsmith CH]]
[[Category: Bountra, C]]
[[Category: Bountra C]]
[[Category: Dong, A]]
[[Category: Dong A]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Lei, M]]
[[Category: Lei M]]
[[Category: Liu, Y]]
[[Category: Liu Y]]
[[Category: Min, J]]
[[Category: Min J]]
[[Category: Qin, S]]
[[Category: Qin S]]
[[Category: Structural genomic]]
[[Category: Mll3]]
[[Category: Phd6]]
[[Category: Sgc]]
[[Category: Transferase]]
Retrieved from "https://proteopedia.org/6mlc"