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| <StructureSection load='6ru7' size='340' side='right'caption='[[6ru7]], [[Resolution|resolution]] 2.08Å' scene=''> | | <StructureSection load='6ru7' size='340' side='right'caption='[[6ru7]], [[Resolution|resolution]] 2.08Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6ru7]] is a 4 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=6RU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RU7 FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RU7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RU7 FirstGlance]. <br> |
| </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08Å</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08Å</td></tr> |
| <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=6ru7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ru7 OCA], [https://pdbe.org/6ru7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ru7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ru7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ru7 ProSAT]</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=6ru7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ru7 OCA], [https://pdbe.org/6ru7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ru7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ru7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ru7 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
| |
| [https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Familial advanced sleep-phase syndrome. The disease is caused by mutations affecting the gene represented in this entry.
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| == Function ==
| |
| [https://www.uniprot.org/uniprot/KC1D_HUMAN KC1D_HUMAN] Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.<ref>PMID:10606744</ref> <ref>PMID:12270943</ref> <ref>PMID:14761950</ref> <ref>PMID:16027726</ref> <ref>PMID:17962809</ref> <ref>PMID:17562708</ref> <ref>PMID:19043076</ref> <ref>PMID:19339517</ref> <ref>PMID:20637175</ref> <ref>PMID:20041275</ref> <ref>PMID:20048001</ref> <ref>PMID:20699359</ref> <ref>PMID:20696890</ref> <ref>PMID:20407760</ref> <ref>PMID:21084295</ref> <ref>PMID:21422228</ref>
| |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
| |
| The p53 homolog TAp63alpha is the transcriptional key regulator of genome integrity in oocytes. After DNA damage, TAp63alpha is activated by multistep phosphorylation involving multiple phosphorylation events by the kinase CK1, which triggers the transition from a dimeric and inactive conformation to an open and active tetramer that initiates apoptosis. By measuring activation kinetics in ovaries and single-site phosphorylation kinetics in vitro with peptides and full-length protein, we show that TAp63alpha phosphorylation follows a biphasic behavior. Although the first two CK1 phosphorylation events are fast, the third one, which constitutes the decisive step to form the active conformation, is slow. Structure determination of CK1 in complex with differently phosphorylated peptides reveals the structural mechanism for the difference in the kinetic behavior based on an unusual CK1/TAp63alpha substrate interaction in which the product of one phosphorylation step acts as an inhibitor for the following one.
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| p63 uses a switch-like mechanism to set the threshold for induction of apoptosis.,Gebel J, Tuppi M, Chaikuad A, Hotte K, Schroder M, Schulz L, Lohr F, Gutfreund N, Finke F, Henrich E, Mezhyrova J, Lehnert R, Pampaloni F, Hummer G, Stelzer EHK, Knapp S, Dotsch V Nat Chem Biol. 2020 Jul 27. pii: 10.1038/s41589-020-0600-3. doi:, 10.1038/s41589-020-0600-3. PMID:32719556<ref>PMID:32719556</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6ru7" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Casein kinase 3D structures|Casein kinase 3D structures]] | | *[[Casein kinase 3D structures|Casein kinase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Homo sapiens]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Arrowsmith CH]] | | [[Category: Arrowsmith CH]] |