2kgi

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[[Image:2kgi.png|left|200px]]
 
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{{STRUCTURE_2kgi| PDB=2kgi | SCENE= }}
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==Solution structure of JARID1A C-terminal PHD finger in complex with H3(1-9)K4me3==
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<StructureSection load='2kgi' size='340' side='right'caption='[[2kgi]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2kgi]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KGI FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kgi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kgi OCA], [https://pdbe.org/2kgi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kgi RCSB], [https://www.ebi.ac.uk/pdbsum/2kgi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kgi ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KDM5A_HUMAN KDM5A_HUMAN] Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity).[UniProtKB:Q3UXZ9]<ref>PMID:11358960</ref> <ref>PMID:15949438</ref> <ref>PMID:17320160</ref> <ref>PMID:17320161</ref> <ref>PMID:17320163</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/kg/2kgi_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2kgi 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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Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.
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===Solution structure of JARID1A C-terminal PHD finger in complex with H3(1-9)K4me3===
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Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.,Wang GG, Song J, Wang Z, Dormann HL, Casadio F, Li H, Luo JL, Patel DJ, Allis CD Nature. 2009 Jun 11;459(7248):847-51. PMID:19430464<ref>PMID:19430464</ref>
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{{ABSTRACT_PUBMED_19430464}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2kgi" style="background-color:#fffaf0;"></div>
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[[2kgi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KGI OCA].
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==See Also==
==See Also==
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*[[Retinoblastoma-binding protein|Retinoblastoma-binding protein]]
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*[[Lysine-specific histone demethylase 3D structures|Lysine-specific histone demethylase 3D structures]]
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*[[Retinoblastoma-binding protein 3D structures|Retinoblastoma-binding protein 3D structures]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:019430464</ref><references group="xtra"/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Patel, D J.]]
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[[Category: Large Structures]]
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[[Category: Song, J.]]
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[[Category: Patel DJ]]
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[[Category: Wang, Z.]]
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[[Category: Song J]]
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[[Category: Chromatin regulator]]
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[[Category: Wang Z]]
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[[Category: Developmental protein]]
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[[Category: Dioxygenase]]
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[[Category: Histone modification]]
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[[Category: Iron]]
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[[Category: Jarid1a]]
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[[Category: Leukemia]]
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[[Category: Metal binding protein]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: Oxidoreductase]]
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[[Category: Phd finger]]
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[[Category: Phosphoprotein]]
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[[Category: Transcription]]
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[[Category: Transcription regulation]]
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[[Category: Zinc-finger]]
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Current revision

Solution structure of JARID1A C-terminal PHD finger in complex with H3(1-9)K4me3

PDB ID 2kgi

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