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| | <StructureSection load='5w0w' size='340' side='right'caption='[[5w0w]], [[Resolution|resolution]] 3.80Å' scene=''> | | <StructureSection load='5w0w' size='340' side='right'caption='[[5w0w]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w0w]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W0W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w0w]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W0W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 3.8Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP2R1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Tiprl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), PPP2CA ([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=5w0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0w OCA], [https://pdbe.org/5w0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w0w RCSB], [https://www.ebi.ac.uk/pdbsum/5w0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0w 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=5w0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0w OCA], [http://pdbe.org/5w0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0w RCSB], [http://www.ebi.ac.uk/pdbsum/5w0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN]] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref> [[http://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref> [[http://www.uniprot.org/uniprot/TIPRL_MOUSE TIPRL_MOUSE]] May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AFX phosphorylated on Ser-140 (gamma-H2AFX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity).[UniProtKB:O75663] | + | [https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</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: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Phosphoprotein phosphatase]]
| + | [[Category: Li J]] |
| - | [[Category: Li, J]] | + | [[Category: Satyshur K]] |
| - | [[Category: Satyshur, K]] | + | [[Category: Wu C]] |
| - | [[Category: Wu, C]] | + | [[Category: Xing Y]] |
| - | [[Category: Xing, Y]] | + | [[Category: Zheng A]] |
| - | [[Category: Zheng, A]] | + | |
| - | [[Category: Complex phosphotase phosphotase regulator]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
2AAA_HUMAN The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.[1]
Publication Abstract from PubMed
Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, alpha4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.
Methylation-regulated decommissioning of multimeric PP2A complexes.,Wu CG, Zheng A, Jiang L, Rowse M, Stanevich V, Chen H, Li Y, Satyshur KA, Johnson B, Gu TJ, Liu Z, Xing Y Nat Commun. 2017 Dec 22;8(1):2272. doi: 10.1038/s41467-017-02405-3. PMID:29273778[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006 May;10(5):575-85. Epub 2006 Mar 30. PMID:16580887 doi:10.1016/j.devcel.2006.03.010
- ↑ Wu CG, Zheng A, Jiang L, Rowse M, Stanevich V, Chen H, Li Y, Satyshur KA, Johnson B, Gu TJ, Liu Z, Xing Y. Methylation-regulated decommissioning of multimeric PP2A complexes. Nat Commun. 2017 Dec 22;8(1):2272. doi: 10.1038/s41467-017-02405-3. PMID:29273778 doi:http://dx.doi.org/10.1038/s41467-017-02405-3
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