6n64

<table><tr><td colspan='2'>[[6n64]] is a 8 chain structure with sequence from [http://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=6N64 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6N64 FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=UNK:UNKNOWN'>UNK</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;'>[[1gxj|1gxj]], [[1gxk|1gxk]], [[2wd5|2wd5]], [[4pup|4pup]], [[5mg8|5mg8]]</div></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Smchd1, Kiaa0650 ([http://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'>[http://proteopedia.org/fgij/fg.htm?mol=6n64 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n64 OCA], [http://pdbe.org/6n64 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n64 RCSB], [http://www.ebi.ac.uk/pdbsum/6n64 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n64 ProSAT]</span></td></tr>

== Function ==

[[http://www.uniprot.org/uniprot/SMHD1_MOUSE SMHD1_MOUSE]] Non-canonical member of the structural maintenance of chromosomes (SMC) protein family that plays a key role in epigenetic silencing by regulating chromatin architecture (PubMed:26091879, PubMed:29887375). Promotes heterochromatin formation in both autosomes and chromosome X, probably by mediating the merge of chromatin compartments (PubMed:23754746, PubMed:23819640, PubMed:26391951, PubMed:28587678, PubMed:29887375). Plays a key role in chromosome X inactivation in females by promoting the spreading of heterochromatin (PubMed:18425126, PubMed:22841499, PubMed:26391951, PubMed:29887375). Recruited to inactivated chromosome X by Xist RNA and acts by mediating the merge of chromatin compartments: promotes random chromatin interactions that span the boundaries of existing structures, leading to create a compartment-less architecture typical of inactivated chromosome X (PubMed:29887375). Required to facilitate Xist RNA spreading (PubMed:29887375). Also required for silencing of a subset of clustered autosomal loci in somatic cells, such as the DUX4 locus (PubMed:23754746, PubMed:23819640, PubMed:28587678). Has ATPase activity; may participate in structural manipulation of chromatin in an ATP-dependent manner as part of its role in gene expression regulation (PubMed:26391951, PubMed:27059856). Also plays a role in DNA repair: localizes to sites of DNA double-strand breaks in response to DNA damage to promote the repair of DNA double-strand breaks (By similarity). Acts by promoting non-homologous end joining (NHEJ) and inhibiting homologous recombination (HR) repair (By similarity). Required during preimplantation development, probably acts by regulating chromatin architecture (PubMed:29900695).[UniProtKB:A6NHR9]<ref>PMID:18425126</ref> <ref>PMID:22841499</ref> <ref>PMID:23754746</ref> <ref>PMID:23819640</ref> <ref>PMID:26091879</ref> <ref>PMID:26391951</ref> <ref>PMID:27059856</ref> <ref>PMID:28587678</ref> <ref>PMID:29887375</ref> <ref>PMID:29900695</ref>

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== Publication Abstract from PubMed ==

Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) is an epigenetic regulator in which polymorphisms cause the human developmental disorder, Bosma arhinia micropthalmia syndrome, and the degenerative disease, facioscapulohumeral muscular dystrophy. SMCHD1 is considered a noncanonical SMC family member because its hinge domain is C-terminal, because it homodimerizes rather than heterodimerizes, and because SMCHD1 contains a GHKL-type, rather than an ABC-type ATPase domain at its N terminus. The hinge domain has been previously implicated in chromatin association; however, the underlying mechanism involved and the basis for SMCHD1 homodimerization are unclear. Here, we used x-ray crystallography to solve the three-dimensional structure of the Smchd1 hinge domain. Together with structure-guided mutagenesis, we defined structural features of the hinge domain that participated in homodimerization and nucleic acid binding, and we identified a functional hotspot required for chromatin localization in cells. This structure provides a template for interpreting the mechanism by which patient polymorphisms within the SMCHD1 hinge domain could compromise function and lead to facioscapulohumeral muscular dystrophy.

Crystal structure of the hinge domain of Smchd1 reveals its dimerization mode and nucleic acid-binding residues.,Chen K, Birkinshaw RW, Gurzau AD, Wanigasuriya I, Wang R, Iminitoff M, Sandow JJ, Young SN, Hennessy PJ, Willson TA, Heckmann DA, Webb AI, Blewitt ME, Czabotar PE, Murphy JM Sci Signal. 2020 Jun 16;13(636). pii: 13/636/eaaz5599. doi:, 10.1126/scisignal.aaz5599. PMID:32546545<ref>PMID:32546545</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 6n64" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Birkinshaw, R W]]

[[Category: Blewitt, M E]]

[[Category: Chen, K]]

[[Category: Czabotar, P E]]

[[Category: Murphy, J M]]

[[Category: Smchd1 epigenetic control dna binding smc protein]]