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| | <StructureSection load='4xb0' size='340' side='right'caption='[[4xb0]], [[Resolution|resolution]] 2.70Å' scene=''> | | <StructureSection load='4xb0' size='340' side='right'caption='[[4xb0]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xb0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XB0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xb0]] is a 2 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=4XB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XB0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLK2, SNK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4xb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xb0 OCA], [https://pdbe.org/4xb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xb0 RCSB], [https://www.ebi.ac.uk/pdbsum/4xb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xb0 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/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </span></td></tr>
| + | |
| - | <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=4xb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xb0 OCA], [http://pdbe.org/4xb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xb0 RCSB], [http://www.ebi.ac.uk/pdbsum/4xb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xb0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLK2_HUMAN PLK2_HUMAN]] Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.<ref>PMID:15242618</ref> <ref>PMID:19001868</ref> <ref>PMID:20531387</ref> <ref>PMID:20352051</ref> | + | [https://www.uniprot.org/uniprot/PLK2_HUMAN PLK2_HUMAN] Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.<ref>PMID:15242618</ref> <ref>PMID:19001868</ref> <ref>PMID:20531387</ref> <ref>PMID:20352051</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polo kinase]]
| + | [[Category: Kim JH]] |
| - | [[Category: Kim, J H]] | + | [[Category: Kim SJ]] |
| - | [[Category: Kim, S J]] | + | [[Category: Ku B]] |
| - | [[Category: Ku, B]] | + | |
| - | [[Category: Plk2]]
| + | |
| - | [[Category: Polo-box domain]]
| + | |
| - | [[Category: Polo-like kinase 2]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PLK2_HUMAN Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.[1] [2] [3] [4]
Publication Abstract from PubMed
Polo-like kinases (Plks) are the key regulators of cell cycle progression, the members of which share a kinase domain and a polo-box domain (PBD) that serves as a protein-binding module. While Plk1 is a promising target for antitumor therapy, Plk2 is regarded as a tumor suppressor even though the two Plks commonly recognize the S-pS/T-P motif through their PBD. Herein, we report the crystal structure of the PBD of Plk2 at 2.7 A. Despite the overall structural similarity with that of Plk1 reflecting their high sequence homology, the crystal structure also contains its own features including the highly ordered loop connecting two subdomains and the absence of 310 -helices in the N-terminal region unlike the PBD of Plk1. Based on the three-dimensional structure, we furthermore could model its interaction with two types of phosphopeptides, one of which was previously screened as the optimal peptide for the PBD of Plk2. Proteins 2015. (c) 2015 Wiley Periodicals, Inc.
Structural analysis of the polo-box domain of human Polo-like kinase 2.,Kim JH, Ku B, Lee KS, Kim SJ Proteins. 2015 Apr 3. doi: 10.1002/prot.24804. PMID:25846005[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Warnke S, Kemmler S, Hames RS, Tsai HL, Hoffmann-Rohrer U, Fry AM, Hoffmann I. Polo-like kinase-2 is required for centriole duplication in mammalian cells. Curr Biol. 2004 Jul 13;14(13):1200-7. PMID:15242618 doi:10.1016/j.cub.2004.06.059
- ↑ Cizmecioglu O, Warnke S, Arnold M, Duensing S, Hoffmann I. Plk2 regulated centriole duplication is dependent on its localization to the centrioles and a functional polo-box domain. Cell Cycle. 2008 Nov 15;7(22):3548-55. Epub 2008 Nov 26. PMID:19001868
- ↑ Chang J, Cizmecioglu O, Hoffmann I, Rhee K. PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 2010 Jul 21;29(14):2395-406. doi: 10.1038/emboj.2010.118. Epub 2010 Jun, 8. PMID:20531387 doi:10.1038/emboj.2010.118
- ↑ Krause A, Hoffmann I. Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplication. PLoS One. 2010 Mar 24;5(3):e9849. doi: 10.1371/journal.pone.0009849. PMID:20352051 doi:10.1371/journal.pone.0009849
- ↑ Kim JH, Ku B, Lee KS, Kim SJ. Structural analysis of the polo-box domain of human Polo-like kinase 2. Proteins. 2015 Apr 3. doi: 10.1002/prot.24804. PMID:25846005 doi:http://dx.doi.org/10.1002/prot.24804
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