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| | <StructureSection load='6z2k' size='340' side='right'caption='[[6z2k]], [[Resolution|resolution]] 4.50Å' scene=''> | | <StructureSection load='6z2k' size='340' side='right'caption='[[6z2k]], [[Resolution|resolution]] 4.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6z2k]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z2K OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6Z2K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6z2k]] is a 12 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=6Z2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z2K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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">Electron Microscopy, [[Resolution|Resolution]] 4.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HDAC1, RPD3L1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DNTTIP1, C20orf167, TDIF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MIDEAS, C14orf117, C14orf43, ELMSAN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_deacetylase Histone deacetylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.98 3.5.1.98] </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=6z2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z2k OCA], [https://pdbe.org/6z2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z2k RCSB], [https://www.ebi.ac.uk/pdbsum/6z2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z2k ProSAT]</span></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=6z2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z2k OCA], [http://pdbe.org/6z2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z2k RCSB], [http://www.ebi.ac.uk/pdbsum/6z2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z2k ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HDAC1_HUMAN HDAC1_HUMAN]] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Component 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:12837748</ref> <ref>PMID:16478997</ref> <ref>PMID:17000776</ref> <ref>PMID:17704056</ref> <ref>PMID:19081374</ref> <ref>PMID:19343227</ref> [[http://www.uniprot.org/uniprot/TDIF1_HUMAN TDIF1_HUMAN]] Shown to enhance TdT activity, in vitro. Also acts as a transcriptional regulator, binding to the consensus sequence 5'-GNTGCATG-3' following an AT-tract. Associates with RAB20 promoter and positively regulates its transcription.<ref>PMID:11473582</ref> <ref>PMID:23874396</ref> | + | [https://www.uniprot.org/uniprot/HDAC1_HUMAN HDAC1_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Component 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:12837748</ref> <ref>PMID:16478997</ref> <ref>PMID:17000776</ref> <ref>PMID:17704056</ref> <ref>PMID:19081374</ref> <ref>PMID:19343227</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Histone deacetylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fairall, L]] | + | [[Category: Fairall L]] |
| - | [[Category: Millard, C J]] | + | [[Category: Millard CJ]] |
| - | [[Category: Ragan, T J]] | + | [[Category: Ragan TJ]] |
| - | [[Category: Saleh, A]] | + | [[Category: Saleh A]] |
| - | [[Category: Savva, C G]] | + | [[Category: Savva CG]] |
| - | [[Category: Schwabe, J W.R]] | + | [[Category: Schwabe JWR]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Hdac1 mideas elmsan1 dnttip1 tdif1 histone deacetylase midac]]
| + | |
| Structural highlights
Function
HDAC1_HUMAN Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Component a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Mice lacking the MiDAC proteins, DNTTIP1 or MIDEAS, die with identical phenotypes during late embryogenesis due to perturbations in gene expression that result in heart malformation and haematopoietic failure. This suggests that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes. Consistent with this, the cryoEM structure of MiDAC reveals a unique and distinctive mode of assembly. Four copies of HDAC1 are positioned at the periphery with outward-facing active sites suggesting that the complex may target multiple nucleosomes implying a processive deacetylase function.
The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure.,Turnbull RE, Fairall L, Saleh A, Kelsall E, Morris KL, Ragan TJ, Savva CG, Chandru A, Millard CJ, Makarova OV, Smith CJ, Roseman AM, Fry AM, Cowley SM, Schwabe JWR Nat Commun. 2020 Jun 26;11(1):3252. doi: 10.1038/s41467-020-17078-8. PMID:32591534[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ammanamanchi S, Freeman JW, Brattain MG. Acetylated sp3 is a transcriptional activator. J Biol Chem. 2003 Sep 12;278(37):35775-80. Epub 2003 Jun 30. PMID:12837748 doi:http://dx.doi.org/10.1074/jbc.M305961200
- ↑ Hung JJ, Wang YT, Chang WC. Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription. Mol Cell Biol. 2006 Mar;26(5):1770-85. PMID:16478997 doi:http://dx.doi.org/10.1128/MCB.26.5.1770-1785.2006
- ↑ Liu Y, Smith PW, Jones DR. Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis. Mol Cell Biol. 2006 Dec;26(23):8683-96. Epub 2006 Sep 25. PMID:17000776 doi:10.1128/MCB.00940-06
- ↑ Wang C, Rauscher FJ 3rd, Cress WD, Chen J. Regulation of E2F1 function by the nuclear corepressor KAP1. J Biol Chem. 2007 Oct 12;282(41):29902-9. Epub 2007 Aug 17. PMID:17704056 doi:10.1074/jbc.M704757200
- ↑ Qiu Z, Ghosh A. A calcium-dependent switch in a CREST-BRG1 complex regulates activity-dependent gene expression. Neuron. 2008 Dec 10;60(5):775-87. doi: 10.1016/j.neuron.2008.09.040. PMID:19081374 doi:http://dx.doi.org/10.1016/j.neuron.2008.09.040
- ↑ Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, Haines JL, Pericak-Vance MA, Buxbaum JD. FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4. PLoS One. 2009;4(4):e5071. doi: 10.1371/journal.pone.0005071. Epub 2009 Apr 3. PMID:19343227 doi:10.1371/journal.pone.0005071
- ↑ Turnbull RE, Fairall L, Saleh A, Kelsall E, Morris KL, Ragan TJ, Savva CG, Chandru A, Millard CJ, Makarova OV, Smith CJ, Roseman AM, Fry AM, Cowley SM, Schwabe JWR. The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure. Nat Commun. 2020 Jun 26;11(1):3252. doi: 10.1038/s41467-020-17078-8. PMID:32591534 doi:http://dx.doi.org/10.1038/s41467-020-17078-8
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