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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]]]]
| | <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]]'> |
| {{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]] }}
| | __TOC__ |
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| | | == Function == |
| | '''Protein phosphatases''' (PP) or '''serine/threonine protein phosphatase''' regulate protein phosphorylation and thus are key in intracellular signal transduction processes.<br /> |
| | * '''PP1''' is a serine/threonine phosphatase and is a key component of the insulin signaling pathway<ref>PMID:9609113</ref>.<br /> |
| | * '''PP1C''' is the catalytic subunit of PP1. |
| | * '''PP1K''' is Mn+2/Mg+2-dependent PP1. |
| | * '''PP2A''' targets proteins in the oncogenic signaling pathways<ref>PMID:11812651</ref>. For PP2A see also [[HEAT Repeat]].<br /> |
| | * '''PP2C''' are Mg/Mn-dependent and are essential for the regulation of cell cycle and stress signaling pathways. For details see<br /> |
| | * <scene name='54/540142/Protein_pp2cm_with_mgii/4'>PP2Cm</scene> |
| | *[[Protein Phosphatase 2C]]<br /> |
| | *[[ABA-regulated Protein Phosphatase 2C]]<br /> |
| | *[[ABA Signaling Pathway]].<br /> |
| | * '''PP4''' regulates a variety of cellular functions<ref>PMID:25562660</ref>.<br /> |
| | * '''PP5''' is activated by lipids and is involved in signal transduction<ref>PMID:11137038</ref>. |
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| | == Disease == |
| | 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 == |
| | | <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. |
| | | *<scene name='54/540142/Cv/6'>Mn+2 ion cofactors coordination site</scene>. |
| | | *<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]] |
| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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| ===PP1A===
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| [[3fxj]], [[3fxk]], [[3fxl]], [[3fxm]], [[3fxo]] – hPP1A + Mn – human<br /> | |
| [[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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| [[4ds8]] – AtPP2C + Pyl3 + Mn<br />
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| [[3rt0]] – AtPP2C (mutant) + Pyl10<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===
| | </StructureSection> |
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| [[1s95]] – hPP5 catalytic domain <br />
| | == References == |
| [[2g62]] – hPP5 <br />
| | <references/> |
| [[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]] |
