5ofb: Difference between revisions

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== Function ==
== Function ==
[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>  
[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>  
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== Publication Abstract from PubMed ==
Missense mutations in MORC2 cause neuropathies including spinal muscular atrophy and Charcot-Marie-Tooth disease. We recently identified MORC2 as an effector of epigenetic silencing by the human silencing hub (HUSH). Here we report the biochemical and cellular activities of MORC2 variants, alongside crystal structures of wild-type and neuropathic forms of a human MORC2 fragment comprising the GHKL-type ATPase module and CW-type zinc finger. This fragment dimerizes upon binding ATP and contains a hinged, functionally critical coiled-coil insertion absent in other GHKL ATPases. We find that dimerization and DNA binding of the MORC2 ATPase module transduce HUSH-dependent silencing. Disease mutations change the dynamics of dimerization by distinct structural mechanisms: destabilizing the ATPase-CW module, trapping the ATP lid, or perturbing the dimer interface. These defects lead to the modulation of HUSH function, thus providing a molecular basis for understanding MORC2-associated neuropathies.
Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms.,Douse CH, Bloor S, Liu Y, Shamin M, Tchasovnikarova IA, Timms RT, Lehner PJ, Modis Y Nat Commun. 2018 Feb 13;9(1):651. doi: 10.1038/s41467-018-03045-x. PMID:29440755<ref>PMID:29440755</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
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Latest revision as of 10:27, 1 May 2024

Crystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation S87LCrystal structure of human MORC2 (residues 1-603) with spinal muscular atrophy mutation S87L

Structural highlights

5ofb 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 2.02Å
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

5ofb, resolution 2.02Å

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