View source for 7zry


==Structure of the 2a splicing variant of the full-length human LSD1 bound to CoREST (delta305)==
<StructureSection load='7zry' size='340' side='right'caption='[[7zry]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zry]] 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=7ZRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZRY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=7zry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zry OCA], [https://pdbe.org/7zry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zry RCSB], [https://www.ebi.ac.uk/pdbsum/7zry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zry ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RCOR1_HUMAN RCOR1_HUMAN] Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation.<ref>PMID:11516394</ref> <ref>PMID:11171972</ref> <ref>PMID:12032298</ref> <ref>PMID:12399542</ref> <ref>PMID:12493763</ref> <ref>PMID:16140033</ref> <ref>PMID:16079794</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The histone demethylase KDM1A is a multi-faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. However, it is unknown whether the fine-tuning of KDM1A splicing isoforms, already shown to regulate neuronal maturation, is crucial for the specification and maintenance of cell identity during cardiogenesis. Here, we discovered a temporal modulation of ubKDM1A and KDM1A+2a during human and mice fetal cardiac development and evaluated their impact on the regulation of cardiac differentiation. We revealed a severely impaired cardiac differentiation in KDM1A(-/-) hESCs that can be rescued by re-expressing ubKDM1A or catalytically impaired ubKDM1A-K661A, but not by KDM1A+2a or KDM1A+2a-K661A. Conversely, KDM1A+2a(-/-) hESCs give rise to functional cardiac cells, displaying increased beating amplitude and frequency and enhanced expression of critical cardiogenic markers. Our findings prove the existence of a divergent scaffolding role of KDM1A splice variants, independent of their enzymatic activity, during hESC differentiation into cardiac cells.

Fine-tuned KDM1A alternative splicing regulates human cardiomyogenesis through an enzymatic-independent mechanism.,Astro V, Ramirez-Calderon G, Pennucci R, Caroli J, Saera-Vila A, Cardona-Londono K, Forastieri C, Fiacco E, Maksoud F, Alowaysi M, Sogne E, Falqui A, Gonzalez F, Montserrat N, Battaglioli E, Mattevi A, Adamo A iScience. 2022 Jun 23;25(7):104665. doi: 10.1016/j.isci.2022.104665. eCollection , 2022 Jul 15. PMID:35856020<ref>PMID:35856020</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zry" style="background-color:#fffaf0;"></div>

==See Also==
*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caroli J]]
[[Category: Mattevi A]]