2jtg

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{{Seed}}
 
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[[Image:2jtg.png|left|200px]]
 
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==Solution structure of the THAP-zinc finger of THAP1==
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The line below this paragraph, containing "STRUCTURE_2jtg", creates the "Structure Box" on the page.
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<StructureSection load='2jtg' size='340' side='right'caption='[[2jtg]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2jtg]] is a 1 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=2JTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JTG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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</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=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_2jtg| PDB=2jtg | SCENE= }}
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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=2jtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jtg OCA], [https://pdbe.org/2jtg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jtg RCSB], [https://www.ebi.ac.uk/pdbsum/2jtg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jtg ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/THAP1_HUMAN THAP1_HUMAN] Defects in THAP1 are the cause of dystonia type 6 (DYT6) [MIM:[https://omim.org/entry/602629 602629]. DYT6 is a primary torsion dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 6 is characterized by onset in early adulthood, cranial or cervical involvement in about half of the cases, and frequent progression to involve multiple body regions.[:]<ref>PMID:19345147</ref> <ref>PMID:19908325</ref> <ref>PMID:19908320</ref> <ref>PMID:19182804</ref> <ref>PMID:20629133</ref> <ref>PMID:20669277</ref> <ref>PMID:20687191</ref> <ref>PMID:20083799</ref> <ref>PMID:20211909</ref> <ref>PMID:21847143</ref> <ref>PMID:20825472</ref> <ref>PMID:21800139</ref> <ref>PMID:21839475</ref> <ref>PMID:21425335</ref> <ref>PMID:21425341</ref> <ref>PMID:21110056</ref> <ref>PMID:22377579</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/THAP1_HUMAN THAP1_HUMAN] DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis.<ref>PMID:12717420</ref> <ref>PMID:17003378</ref> <ref>PMID:20200153</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/jt/2jtg_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/main_output.php?pdb_ID=2jtg 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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THAP1, the founding member of a previously uncharacterized large family of cellular proteins (THAP proteins), is a sequence-specific DNA-binding factor that has recently been shown to regulate cell proliferation through modulation of pRb/E2F cell cycle target genes. THAP1 shares its DNA-binding THAP zinc finger domain with Drosophila P element transposase, zebrafish E2F6, and several nematode proteins interacting genetically with the retinoblastoma protein pRb. In this study, we report the three-dimensional structure and structure-function relationships of the THAP zinc finger of human THAP1. Deletion mutagenesis and multidimensional NMR spectroscopy revealed that the THAP domain of THAP1 is an atypical zinc finger of approximately 80 residues, distinguished by the presence between the C2CH zinc coordinating residues of a short antiparallel beta-sheet interspersed by a long loop-helix-loop insertion. Alanine scanning mutagenesis of this loop-helix-loop motif resulted in the identification of a number of critical residues for DNA recognition. NMR chemical shift perturbation analysis was used to further characterize the residues involved in DNA binding. The combination of the mutagenesis and NMR data allowed the mapping of the DNA binding interface of the THAP zinc finger to a highly positively charged area harboring multiple lysine and arginine residues. Together, these data represent the first structure-function analysis of a functional THAP domain, with demonstrated sequence-specific DNA binding activity. They also provide a structural framework for understanding DNA recognition by this atypical zinc finger, which defines a novel family of cellular factors linked to cell proliferation and pRb/E2F cell cycle pathways in humans, fish, and nematodes.
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===Solution structure of the THAP-zinc finger of THAP1===
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Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways.,Bessiere D, Lacroix C, Campagne S, Ecochard V, Guillet V, Mourey L, Lopez F, Czaplicki J, Demange P, Milon A, Girard JP, Gervais V J Biol Chem. 2008 Feb 15;283(7):4352-63. Epub 2007 Dec 11. PMID:18073205<ref>PMID:18073205</ref>
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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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The line below this paragraph, {{ABSTRACT_PUBMED_18073205}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2jtg" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18073205 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18073205}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2JTG is a 1 chain structure of 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=2JTG OCA].
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==Reference==
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<ref group="xtra">PMID:18073205</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Bessiere, D.]]
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[[Category: Large Structures]]
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[[Category: Campagne, S.]]
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[[Category: Bessiere D]]
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[[Category: Gervais, V.]]
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[[Category: Campagne S]]
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[[Category: Milon, A.]]
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[[Category: Gervais V]]
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[[Category: Ccch]]
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[[Category: Milon A]]
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[[Category: Dna-binding]]
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[[Category: Metal binding protein]]
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[[Category: Metal-binding]]
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[[Category: Thap]]
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[[Category: Zinc finger]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 09:28:08 2009''
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Current revision

Solution structure of the THAP-zinc finger of THAP1

PDB ID 2jtg

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