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==Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation T424R==
==Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation T424R==
<StructureSection load='5ofa' size='340' side='right' caption='[[5ofa]], [[Resolution|resolution]] 2.57&Aring;' scene=''>
<StructureSection load='5ofa' size='340' side='right'caption='[[5ofa]], [[Resolution|resolution]] 2.57&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5ofa]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OFA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OFA FirstGlance]. <br>
<table><tr><td colspan='2'>[[5ofa]] 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=5OFA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OFA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.57&#8491;</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=5ofa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofa OCA], [http://pdbe.org/5ofa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ofa RCSB], [http://www.ebi.ac.uk/pdbsum/5ofa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofa ProSAT]</span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5ofa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ofa OCA], [https://pdbe.org/5ofa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ofa RCSB], [https://www.ebi.ac.uk/pdbsum/5ofa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ofa ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry.  
[https://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN]] Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). May act as a transcriptional repressor (PubMed:20225202). Down-regulates CA9 expression (PubMed:20110259).<ref>PMID:20110259</ref> <ref>PMID:20225202</ref> <ref>PMID:24286864</ref> 
[https://www.uniprot.org/uniprot/MORC2_HUMAN MORC2_HUMAN] Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). May act as a transcriptional repressor (PubMed:20225202). Down-regulates CA9 expression (PubMed:20110259).<ref>PMID:20110259</ref> <ref>PMID:20225202</ref> <ref>PMID:24286864</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease.
 
Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.,Tchasovnikarova IA, Timms RT, Douse CH, Roberts RC, Dougan G, Kingston RE, Modis Y, Lehner PJ Nat Genet. 2017 Jul;49(7):1035-1044. doi: 10.1038/ng.3878. Epub 2017 Jun 5. PMID:28581500<ref>PMID:28581500</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ofa" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Douse, C H]]
[[Category: Homo sapiens]]
[[Category: Liu, Y]]
[[Category: Large Structures]]
[[Category: Modis, Y]]
[[Category: Douse CH]]
[[Category: Charcot-marie-tooth disease]]
[[Category: Liu Y]]
[[Category: Chromatin remodeler]]
[[Category: Modis Y]]
[[Category: Coiled-coil]]
[[Category: Cw domain]]
[[Category: Dna binding protein]]
[[Category: Epigenetic silencing]]
[[Category: Ghkl atpase]]
[[Category: Nuclear protein]]
[[Category: Spinal muscular atrophy]]
[[Category: Transcriptional repressor]]

Latest revision as of 10:27, 1 May 2024

Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation T424RCrystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation T424R

Structural highlights

5ofa is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.57Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MORC2_HUMAN The disease is caused by mutations affecting the gene represented in this entry.

Function

MORC2_HUMAN Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). May act as a transcriptional repressor (PubMed:20225202). Down-regulates CA9 expression (PubMed:20110259).[1] [2] [3]

References

  1. ↑ Shao Y, Li Y, Zhang J, Liu D, Liu F, Zhao Y, Shen T, Li F. Involvement of histone deacetylation in MORC2-mediated down-regulation of carbonic anhydrase IX. Nucleic Acids Res. 2010 May;38(9):2813-24. doi: 10.1093/nar/gkq006. Epub 2010 Jan, 27. PMID:20110259 doi:http://dx.doi.org/10.1093/nar/gkq006
  2. ↑ Wang GL, Wang CY, Cai XZ, Chen W, Wang XH, Li F. Identification and expression analysis of a novel CW-type zinc finger protein MORC2 in cancer cells. Anat Rec (Hoboken). 2010 Jun;293(6):1002-9. doi: 10.1002/ar.21119. PMID:20225202 doi:http://dx.doi.org/10.1002/ar.21119
  3. ↑ Sanchez-Solana B, Li DQ, Kumar R. Cytosolic functions of MORC2 in lipogenesis and adipogenesis. Biochim Biophys Acta. 2014 Feb;1843(2):316-26. doi: 10.1016/j.bbamcr.2013.11.012., Epub 2013 Nov 25. PMID:24286864 doi:http://dx.doi.org/10.1016/j.bbamcr.2013.11.012

5ofa, resolution 2.57Å

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