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| | <StructureSection load='5ioh' size='340' side='right'caption='[[5ioh]], [[Resolution|resolution]] 2.57Å' scene=''> | | <StructureSection load='5ioh' size='340' side='right'caption='[[5ioh]], [[Resolution|resolution]] 2.57Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ioh]] is a 4 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=5IOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IOH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ioh]] 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=5IOH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IOH FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5inb|5inb]], [[5j28|5j28]]</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]] 2.566Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP1CA, PPP1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CDCA2 ([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=5ioh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ioh OCA], [https://pdbe.org/5ioh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ioh RCSB], [https://www.ebi.ac.uk/pdbsum/5ioh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ioh 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/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=5ioh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ioh OCA], [http://pdbe.org/5ioh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ioh RCSB], [http://www.ebi.ac.uk/pdbsum/5ioh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ioh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN]] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref> [[http://www.uniprot.org/uniprot/CDCA2_HUMAN CDCA2_HUMAN]] Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates.<ref>PMID:16492807</ref> <ref>PMID:16998479</ref> | + | [https://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoprotein phosphatase]]
| + | [[Category: Kumar GS]] |
| - | [[Category: Kumar, G S]] | + | [[Category: Page R]] |
| - | [[Category: Page, R]] | + | [[Category: Peti W]] |
| - | [[Category: Peti, W]] | + | |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| - | [[Category: Ki-67]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Pp1 alpha]]
| + | |
| - | [[Category: Repoman]]
| + | |
| Structural highlights
Function
PP1A_HUMAN Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.[1]
Publication Abstract from PubMed
Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (Booth et al., 2014). Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provide immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes.
The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism.,Kumar GS, Gokhan E, De Munter S, Bollen M, Vagnarelli P, Peti W, Page R Elife. 2016 Aug 30;5. pii: e16539. doi: 10.7554/eLife.16539. PMID:27572260[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mi J, Guo C, Brautigan DL, Larner JM. Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. PMID:17283141 doi:10.1158/0008-5472.CAN-06-3071
- ↑ Kumar GS, Gokhan E, De Munter S, Bollen M, Vagnarelli P, Peti W, Page R. The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism. Elife. 2016 Aug 30;5. pii: e16539. doi: 10.7554/eLife.16539. PMID:27572260 doi:http://dx.doi.org/10.7554/eLife.16539
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