3kv4

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{{STRUCTURE_3kv4| PDB=3kv4 | SCENE= }}
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==Structure of PHF8 in complex with histone H3==
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===Structure of PHF8 in complex with histone H3===
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<StructureSection load='3kv4' size='340' side='right' caption='[[3kv4]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
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{{ABSTRACT_PUBMED_20023638}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3kv4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KV4 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OGA:N-OXALYLGLYCINE'>OGA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kv5|3kv5]], [[3kv6|3kv6]], [[3kv9|3kv9]], [[3kva|3kva]], [[3kvb|3kvb]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA1111, PHF8, ZNF422 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3kv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kv4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kv4 RCSB], [http://www.ebi.ac.uk/pdbsum/3kv4 PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Defects in PHF8 are the cause of mental retardation syndromic X-linked Siderius type (MRXSSD) [MIM:[http://omim.org/entry/300263 300263]]. A disorder characterized by mild to borderline mental retardation with or without cleft lip/cleft palate.<ref>PMID:20548336</ref> <ref>PMID:20346720</ref> <ref>PMID:20421419</ref> <ref>PMID:20208542</ref> <ref>PMID:20622853</ref> <ref>PMID:20622854</ref> <ref>PMID:20101266</ref> <ref>PMID:16199551</ref> <ref>PMID:17661819</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.<ref>PMID:20531378</ref> <ref>PMID:20548336</ref> <ref>PMID:19843542</ref> <ref>PMID:20346720</ref> <ref>PMID:20421419</ref> <ref>PMID:20208542</ref> <ref>PMID:20622853</ref> <ref>PMID:20622854</ref> <ref>PMID:20101266</ref> <ref>PMID:20023638</ref> [[http://www.uniprot.org/uniprot/H3L_HUMAN H3L_HUMAN]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes.<ref>PMID:21274551</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kv/3kv4_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Combinatorial readout of multiple covalent histone modifications is poorly understood. We provide insights into how an activating histone mark, in combination with linked repressive marks, is differentially 'read' by two related human demethylases, PHF8 and KIAA1718 (also known as JHDM1D). Both enzymes harbor a plant homeodomain (PHD) that binds Lys4-trimethylated histone 3 (H3K4me3) and a jumonji domain that demethylates either H3K9me2 or H3K27me2. The presence of H3K4me3 on the same peptide as H3K9me2 makes the doubly methylated peptide a markedly better substrate of PHF8, whereas the presence of H3K4me3 has the opposite effect, diminishing the H3K9me2 demethylase activity of KIAA1718 without adversely affecting its H3K27me2 activity. The difference in substrate specificity between the two is explained by PHF8 adopting a bent conformation, allowing each of its domains to engage its respective target, whereas KIAA1718 adopts an extended conformation, which prevents its access to H3K9me2 by its jumonji domain when its PHD engages H3K4me3.
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==Disease==
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Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases.,Horton JR, Upadhyay AK, Qi HH, Zhang X, Shi Y, Cheng X Nat Struct Mol Biol. 2010 Jan;17(1):38-43. Epub 2009 Dec 20. PMID:20023638<ref>PMID:20023638</ref>
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Defects in PHF8 are the cause of mental retardation syndromic X-linked Siderius type (MRXSSD) [MIM:[http://omim.org/entry/300263 300263]]. A disorder characterized by mild to borderline mental retardation with or without cleft lip/cleft palate.<ref>PMID:20548336</ref><ref>PMID:20346720</ref><ref>PMID:20421419</ref><ref>PMID:20208542</ref><ref>PMID:20622853</ref><ref>PMID:20622854</ref><ref>PMID:20101266</ref><ref>PMID:16199551</ref><ref>PMID:17661819</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/PHF8_HUMAN PHF8_HUMAN]] Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.<ref>PMID:20531378</ref><ref>PMID:20548336</ref><ref>PMID:19843542</ref><ref>PMID:20346720</ref><ref>PMID:20421419</ref><ref>PMID:20208542</ref><ref>PMID:20622853</ref><ref>PMID:20622854</ref><ref>PMID:20101266</ref><ref>PMID:20023638</ref> [[http://www.uniprot.org/uniprot/H3L_HUMAN H3L_HUMAN]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes.<ref>PMID:21274551</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[3kv4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KV4 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:020023638</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cheng, X.]]
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[[Category: Cheng, X]]
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[[Category: Horton, J R.]]
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[[Category: Horton, J R]]
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[[Category: Qi, H H.]]
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[[Category: Qi, H H]]
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[[Category: Shi, Y.]]
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[[Category: Shi, Y]]
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[[Category: Upadhyay, A K.]]
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[[Category: Upadhyay, A K]]
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[[Category: Zhang, X.]]
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[[Category: Zhang, X]]
[[Category: Covalent histone modification]]
[[Category: Covalent histone modification]]
[[Category: Epigenetic]]
[[Category: Epigenetic]]

Revision as of 16:04, 18 December 2014

Structure of PHF8 in complex with histone H3

3kv4, resolution 2.19Å

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