2xaf: Difference between revisions

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<StructureSection load='2xaf' size='340' side='right'caption='[[2xaf]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
<StructureSection load='2xaf' size='340' side='right'caption='[[2xaf]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2xaf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XAF FirstGlance]. <br>
<table><tr><td colspan='2'>[[2xaf]] 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=2XAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XAF FirstGlance]. <br>
</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>, <scene name='pdbligand=TCF:3-(4-BROMOPHENYL)PROPANAMIDE'>TCF</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]] 3.25&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2x0l|2x0l]], [[2uxx|2uxx]], [[2iw5|2iw5]], [[2com|2com]], [[2xaj|2xaj]], [[2v1d|2v1d]], [[2uxn|2uxn]], [[2h94|2h94]], [[2xag|2xag]], [[2xaq|2xaq]], [[2xah|2xah]], [[2xas|2xas]]</div></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>, <scene name='pdbligand=TCF:3-(4-BROMOPHENYL)PROPANAMIDE'>TCF</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=2xaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xaf OCA], [https://pdbe.org/2xaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xaf RCSB], [https://www.ebi.ac.uk/pdbsum/2xaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xaf ProSAT]</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=2xaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xaf OCA], [https://pdbe.org/2xaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xaf RCSB], [https://www.ebi.ac.uk/pdbsum/2xaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xaf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/KDM1A_HUMAN KDM1A_HUMAN]] Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. 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.<ref>PMID:12032298</ref> <ref>PMID:15620353</ref> <ref>PMID:16079795</ref> <ref>PMID:17805299</ref> <ref>PMID:20228790</ref> [[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> 
[https://www.uniprot.org/uniprot/KDM1A_HUMAN KDM1A_HUMAN] Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. 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.<ref>PMID:12032298</ref> <ref>PMID:15620353</ref> <ref>PMID:16079795</ref> <ref>PMID:17805299</ref> <ref>PMID:20228790</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Binda, C]]
[[Category: Binda C]]
[[Category: Botrugno, O A]]
[[Category: Botrugno OA]]
[[Category: Ciossani, G]]
[[Category: Ciossani G]]
[[Category: Cirilli, R]]
[[Category: Cirilli R]]
[[Category: Edmondson, D E]]
[[Category: Edmondson DE]]
[[Category: Forneris, F]]
[[Category: Forneris F]]
[[Category: Karytinos, A]]
[[Category: Karytinos A]]
[[Category: Mai, A]]
[[Category: Mai A]]
[[Category: Mattevi, A]]
[[Category: Mattevi A]]
[[Category: Minucci, S]]
[[Category: Minucci S]]
[[Category: Pilotto, S]]
[[Category: Pilotto S]]
[[Category: Romanenghi, M]]
[[Category: Romanenghi M]]
[[Category: Tardugno, M]]
[[Category: Tardugno M]]
[[Category: Valente, S]]
[[Category: Valente S]]
[[Category: Amine oxidase]]
[[Category: Chromatin regulator]]
[[Category: Chromatin remodelling]]
[[Category: Histone inhibitor binding]]
[[Category: Methylation]]
[[Category: Nucleosome core]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase-repressor complex]]
[[Category: Transcription]]

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