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| | ==Crystal Structure of the CK2 Tetrameric Holoenzyme== | | ==Crystal Structure of the CK2 Tetrameric Holoenzyme== |
| - | <StructureSection load='4dgl' size='340' side='right' caption='[[4dgl]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4dgl' size='340' side='right'caption='[[4dgl]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dgl]] is a 4 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=4DGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DGL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dgl]] 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=4DGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DGL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jwh|1jwh]]</td></tr>
| + | <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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSNK2B, CK2N, G5A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CSNK2A1, CK2A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4dgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dgl OCA], [https://pdbe.org/4dgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dgl RCSB], [https://www.ebi.ac.uk/pdbsum/4dgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dgl ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=4dgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dgl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dgl RCSB], [http://www.ebi.ac.uk/pdbsum/4dgl PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CSK2B_HUMAN CSK2B_HUMAN]] Participates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.<ref>PMID:11239457</ref> <ref>PMID:16818610</ref> [[http://www.uniprot.org/uniprot/CSK21_HUMAN CSK21_HUMAN]] Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.<ref>PMID:11239457</ref> <ref>PMID:11704824</ref> <ref>PMID:16193064</ref> <ref>PMID:19188443</ref> | + | [https://www.uniprot.org/uniprot/CSK2B_HUMAN CSK2B_HUMAN] Participates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.<ref>PMID:11239457</ref> <ref>PMID:16818610</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | CK2 is a Ser/Thr protein kinase essential for cell viability whose activity is anomalously high in several cancers. CK2 is a validated target for cancer therapy with one small molecule inhibitor in phase I clinical trials. This enzyme is not regulated by mechanisms common to other protein kinases, and how its activity is controlled is still unclear. We present a new crystal structure of the CK2 holoenzyme that supports an autoinhibitory mechanism of regulation whereby the beta-subunit plays an essential role in the formation of inactive polymeric assemblies. The derived structural model of (down)regulation by aggregation contributes to the interpretation of biochemical and functional data and paves the way for new strategies in the modulation of CK2 activity and for the design of non-ATP-competitive inhibitors targeting the interaction between the alpha catalytic and the beta regulatory subunits.
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| - | Structural Determinants of Protein Kinase CK2 Regulation by Autoinhibitory Polymerization.,Lolli G, Pinna LA, Battistutta R ACS Chem Biol. 2012 Apr 20. PMID:22506723<ref>PMID:22506723</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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| | ==See Also== | | ==See Also== |
| - | *[[Casein kinase|Casein kinase]] | + | *[[Casein kinase 3D structures|Casein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Large Structures]] |
| - | [[Category: Battistutta, R]] | + | [[Category: Battistutta R]] |
| - | [[Category: Lolli, G]] | + | [[Category: Lolli G]] |
| - | [[Category: Protein kinase]]
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| - | [[Category: Transferase]]
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