6tw2

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<StructureSection load='6tw2' size='340' side='right'caption='[[6tw2]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='6tw2' size='340' side='right'caption='[[6tw2]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6tw2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TW2 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6tw2]] is a 1 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=6TW2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TW2 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=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</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=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=V25:ETHYL+3-[(E)-2-AMINO-1-CYANOETHENYL]-6,7-DICHLORO-1-METHYL-1H-INDOLE-2-CARBOXYLATE'>V25</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vag|2vag]]</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=6tw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tw2 OCA], [https://pdbe.org/6tw2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tw2 RCSB], [https://www.ebi.ac.uk/pdbsum/6tw2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tw2 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></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=6tw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tw2 OCA], [http://pdbe.org/6tw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tw2 RCSB], [http://www.ebi.ac.uk/pdbsum/6tw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tw2 ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
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[https://www.uniprot.org/uniprot/CLK1_HUMAN CLK1_HUMAN] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA.<ref>PMID:10480872</ref> <ref>PMID:19168442</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Homeothermic organisms maintain their core body temperature in a narrow, tightly controlled range. Whether and how subtle circadian oscillations or disease-associated changes in core body temperature are sensed and integrated in gene expression programs remain elusive. Furthermore, a thermo-sensor capable of sensing the small temperature differentials leading to temperature-dependent sex determination (TSD) in poikilothermic reptiles has not been identified. Here, we show that the activity of CDC-like kinases (CLKs) is highly responsive to physiological temperature changes, which is conferred by structural rearrangements within the kinase activation segment. Lower body temperature activates CLKs resulting in strongly increased phosphorylation of SR proteins in vitro and in vivo. This globally controls temperature-dependent alternative splicing and gene expression, with wide implications in circadian, tissue-specific, and disease-associated settings. This temperature sensor is conserved across evolution and adapted to growth temperatures of diverse poikilotherms. The dynamic temperature range of reptilian CLK homologs suggests a role in TSD.
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A Conserved Kinase-Based Body-Temperature Sensor Globally Controls Alternative Splicing and Gene Expression.,Haltenhof T, Kotte A, De Bortoli F, Schiefer S, Meinke S, Emmerichs AK, Petermann KK, Timmermann B, Imhof P, Franz A, Loll B, Wahl MC, Preussner M, Heyd F Mol Cell. 2020 Feb 7. pii: S1097-2765(20)30049-6. doi:, 10.1016/j.molcel.2020.01.028. PMID:32059760<ref>PMID:32059760</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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<div class="pdbe-citations 6tw2" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Dual specificity protein kinase 3D structures|Dual specificity protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Dual-specificity kinase]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Haltenhof, T]]
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[[Category: Haltenhof T]]
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[[Category: Heyd, F]]
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[[Category: Heyd F]]
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[[Category: Loll, B]]
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[[Category: Loll B]]
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[[Category: Wahl, M C]]
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[[Category: Wahl MC]]
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[[Category: Nucleus]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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[[Category: Tyrosine-protein kinase]]
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Current revision

Re-refined crystal structure of di-phosphorylated human CLK1 in complex with a novel substituted indole inhibitor

PDB ID 6tw2

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