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Protein phosphatase

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[[Image:3k7v.png|left|200px|thumb|Crystal structure of human PP2A catalytic (pink) and regulatory (grey) subunits complex with tumor-inducing toxin binding protein [[3k7v]]]]
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<StructureSection load='' size='350' side='right' scene='54/540142/Cv/1' caption='Human PP2A catalytic (green) and regulatory (cyan) subunits complex with tumor-inducing toxin and sulfate [[3k7v]]'>
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{{STRUCTURE_3k7v| PDB=3k7v | SIZE=400| SCENE= |right|CAPTION=Human PP2A catalytic (pink) and regulatory (grey) subunits complex with tumor-inducing toxin and sulfate [[3k7v]] }}
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__TOC__
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== Function ==
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'''Protein phosphatases''' (PP) or '''serine/threonine protein phosphatase''' regulate protein phosphorylation and thus are key in intracellular signal transduction processes.<br />
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* '''PP1''' is a serine/threonine phosphatase and is a key component of the insulin signaling pathway<ref>PMID:9609113</ref>.<br />
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* '''PP2A''' targets proteins in the oncogenic signaling pathways<ref>PMID:11812651</ref>. For PP2A see also [[HEAT Repeat]].<br />
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* '''PP2C''' are Mg/Mn-dependent and are essential for the regulation of cell cycle and stress signaling pathways. For details see<br />
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* <scene name='54/540142/Protein_pp2cm_with_mgii/4'>PP2Cm</scene>
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*[[Protein Phosphatase 2C]]<br />
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*[[ABA-regulated Protein Phosphatase 2C]]<br />
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*[[ABA Signaling Pathway]].<br />
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* '''PP4''' regulates a variety of cellular functions<ref>PMID:25562660</ref>.<br />
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* '''PP5''' is activated by lipids and is involved in signal transduction<ref>PMID:11137038</ref>.
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== Disease ==
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Mutations in PP2A are found in many solid cancers and leukemias. PP2A-activating drugs are possible candidates for cancer therapeutics protocols<ref>PMID:23639323</ref>. Development of Alzheimer disease drugs could be based on restoration of PP2A activity<ref>PMID:21605044</ref>.
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== Structural highlights ==
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<scene name='54/540142/Cv/5'>Human PP2A catalytic (green) and regulatory (cyan) subunits complex with tumor-inducing toxin</scene>. Algal toxin binds at the surface pocket of the PP2A catalytic subunit which contains the Mn+2 ion cofactors<ref>PMID:19916524</ref>. Water molecule are shown as red sphere.
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*<scene name='54/540142/Cv/6'>Mn+2 ion cofactors coordination site</scene>.
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*<scene name='54/540142/Cv/7'>Whole binding site</scene>.
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'''Protein phosphatases''' (PP) regular protein phosphorylation and thus are key in intracellular signal transduction processes. PP1 is a serine/threonine phosphatase. PP2A targets proteins in the oncogenic signaling pathways. PP2C are Mg/Mn- dependent and are essential for the regulation of cell cycle and stress signaling pathways. PP4 regulates a variety of cellular functions. PP5 is activated by lipids and is involved in signal transduction. For PP2A see also [[HEAT Repeat]].
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== 3D Structures of protein phosphatase==
== 3D Structures of protein phosphatase==
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[[Protein phosphatase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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===PP1A===
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[[3fxj]], [[3fxk]], [[3fxl]], [[3fxm]], [[3fxo]] – hPP1A + Mn – human<br />
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[[4da1]] – hPP1K + Mn<br />
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[[1jk7]], [[1u32]], [[2bcd]], [[2bdx]], [[3e7a]], [[3e7b]] – hPP1 catalytic subunit + tumor-inducing toxin<br />
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[[1fjm]] – PP1 + tumor-inducing toxin - rabbit<br />
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[[3egg]] – hPP1 catalytic subunit + spinophilin<br />
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[[3hvq]] – hPP1 catalytic subunit + neuroabin<br />
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[[3n5u]] – hPP1A catalytic subunit + retinoblastoma-associated protein<br />
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[[3v4y]] – hPP1A catalytic subunit + PP1 nuclear inhibitor<br />
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[[4g9j]] – hPP1A catalytic subunit + peptide<br />
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[[3egh]] – hPP1 catalytic subunit + spinophilin + toxin<br />
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[[1it6]] – hPP1 catalytic subunit + calyculin<br />
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[[1s70]] – hPP1 catalytic subunit (mutant) + smooth muscle myosin phosphatase<br />
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[[2o8a]], [[2o8g]] – PP1C catalytic subunit + inhibitor - rat<br />
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[[2rlt]] – PP1 regulatory subunit – pig - NMR<br />
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===PP2A===
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[[1b3u]], [[2ixm]], [[2jak]], [[2g62]] – hPP2A regulatory subunit <br />
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[[2pkg]] – hPP2A regulatory subunit + small T antigen<br />
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[[2pf4]] – PP2A regulatory subunit + small T antigen - mouse<br />
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[[2ie3]], [[2ie4]], [[2npp]], [[2nyl]], [[2nym]], [[2iae]], [[3dw8]], [[3k7v]], [[3k7w]] – hPP2A catalytic + regulatory subunit + tumor-inducing toxin<br />
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[[3fga]] – hPP2C catalytic + regulatory subunit + tumor-inducing toxin + Sgo<br />
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[[3c5w]] – hPP2A catalytic + regulatory subunit + PP2A-specific methyltransferase<br />
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[[3c5w]], [[3p71]] – hPP2A catalytic subunit + leucine carboxyl methyltransferase<br />
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===PP2C===
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[[1a6q]] – hPP2C <br />
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[[2iq1]] – hPP2C κ <br />
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[[2p8e]] – hPP2C β<br />
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[[2cm1]] – PP2C + Mn – Micobacterium tuberculosis<br />
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[[3d8k]] – PP2C – Toxoplasma gondii<br />
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[[3jrq]], [[3kdj]], [[3nmn]] – AtPP2C + Pyl1 – Arabidopsis thaliana<br />
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[[3nmt]], [[3kb3]], [[3nmv]], [[3ujl]] – AtPP2C + Pyl2<br />
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[[4la7]], [[4lg5]], [4lga]], [[4lgb]] – AtPP2C + Pyl2 + ligand<br />
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[[4ds8]] – AtPP2C + Pyl3 + Mn<br />
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[[3rt0]] – AtPP2C (mutant) + Pyl10<br />
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[[4n0g]] – AtPP2C + Pyl13<br />
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[[3qn1]], [[3zvu]] – AtPP2C + Pyr1<br />
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[[3ujg]] – AtPP2C + SNRK2<br />
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[[3ujk]] – AtPP2C <br />
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===PP5===
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</StructureSection>
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[[1s95]] – hPP5 catalytic domain <br />
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== References ==
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[[2g62]] – hPP5 <br />
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<references/>
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[[2bug]] – hPP5 tetratricopeptide domain + Hsp90 peptide<br />
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[[3h60]] – hPP5 catalytic domain + Mn<br />
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[[3h61]], [[3h62]], [[3h63]], [[3h64]] – hPP5 catalytic domain + Mn + inhibitor<br />
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[[3h66]] – hPP5 catalytic domain + Zn <br />
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[[3h67]], [[3h68]], [[3h69]] – hPP5 catalytic domain + Zn + inhibitor<br />
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human PP2A catalytic (green) and regulatory (cyan) subunits complex with tumor-inducing toxin and sulfate 3k7v

Drag the structure with the mouse to rotate

References

  1. ↑ Ragolia L, Begum N. Protein phosphatase-1 and insulin action. Mol Cell Biochem. 1998 May;182(1-2):49-58. PMID:9609113
  2. ↑ Resjo S, Goransson O, Harndahl L, Zolnierowicz S, Manganiello V, Degerman E. Protein phosphatase 2A is the main phosphatase involved in the regulation of protein kinase B in rat adipocytes. Cell Signal. 2002 Mar;14(3):231-8. PMID:11812651
  3. ↑ Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR. Centromeric binding and activity of Protein Phosphatase 4. Nat Commun. 2015 Jan 6;6:5894. doi: 10.1038/ncomms6894. PMID:25562660 doi:http://dx.doi.org/10.1038/ncomms6894
  4. ↑ Chinkers M. Protein phosphatase 5 in signal transduction. Trends Endocrinol Metab. 2001 Jan-Feb;12(1):28-32. PMID:11137038
  5. ↑ Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol. 2013 May;14(6):e229-38. doi: 10.1016/S1470-2045(12)70558-2. PMID:23639323 doi:http://dx.doi.org/10.1016/S1470-2045(12)70558-2
  6. ↑ Rudrabhatla P, Pant HC. Role of protein phosphatase 2A in Alzheimer's disease. Curr Alzheimer Res. 2011 Sep;8(6):623-32. PMID:21605044
  7. ↑ Huhn J, Jeffrey PD, Larsen K, Rundberget T, Rise F, Cox NR, Arcus V, Shi Y, Miles CO. A structural basis for the reduced toxicity of dinophysistoxin-2. Chem Res Toxicol. 2009 Nov;22(11):1782-6. PMID:19916524 doi:10.1021/tx9001622
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