Protein phosphatase: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
Michal Harel (talk | contribs)
31,761 edits
No edit summary
Michal Harel (talk | contribs)
31,761 edits
No edit summary
 
(30 intermediate revisions by 4 users not shown)
Line 1: Line 1:
[[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__


   
== 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>.  


== 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>.


 
== 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>.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
'''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]].
 
== 3D Structures of protein phosphatase==
== 3D Structures of protein phosphatase==
[[Protein phosphatase 3D structures]]
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
===PP1A===
 
[[3fxj]], [[3fxk]], [[3fxl]], [[3fxm]], [[3fxo]] – hPP1A + Mn – human<br />
[[4da1]] – hPP1K + Mn<br />
[[1jk7]], [[1u32]], [[2bcd]], [[2bdx]], [[3e7a]], [[3e7b]] – hPP1 catalytic subunit + tumor-inducing toxin<br />
[[1fjm]] – PP1 + tumor-inducing toxin - rabbit<br />
[[3egg]] – hPP1 catalytic subunit + spinophilin<br />
[[3hvq]] – hPP1 catalytic subunit + neuroabin<br />
[[3n5u]] – hPP1A catalytic subunit + retinoblastoma-associated protein<br />
[[3v4y]] – hPP1A catalytic subunit + PP1 nuclear inhibitor<br />
[[4g9j]] – hPP1A catalytic subunit + peptide<br />
[[3egh]] – hPP1 catalytic subunit + spinophilin + toxin<br />
[[1it6]] – hPP1 catalytic subunit + calyculin<br />
[[1s70]] – hPP1 catalytic subunit (mutant) + smooth muscle myosin phosphatase<br />
[[2o8a]], [[2o8g]] – PP1C catalytic subunit + inhibitor - rat<br />
[[2rlt]] – PP1 regulatory subunit – pig - NMR<br />
 
===PP2A===
 
[[1b3u]], [[2ixm]], [[2jak]], [[2g62]] – hPP2A regulatory subunit <br />
[[2pkg]] – hPP2A regulatory subunit + small T antigen<br />
[[2pf4]] – PP2A regulatory subunit + small T antigen - mouse<br />
[[2ie3]], [[2ie4]], [[2npp]], [[2nyl]], [[2nym]], [[2iae]], [[3dw8]], [[3k7v]], [[3k7w]] – hPP2A catalytic + regulatory subunit + tumor-inducing toxin<br />
[[3fga]] – hPP2C catalytic + regulatory subunit + tumor-inducing toxin + Sgo<br />
[[3c5w]] – hPP2A catalytic + regulatory subunit + PP2A-specific methyltransferase<br />
[[3c5w]], [[3p71]] – hPP2A catalytic subunit + leucine carboxyl methyltransferase<br />
 
===PP2C===
 
[[1a6q]] – hPP2C <br />
[[2iq1]] – hPP2C κ <br />
[[2p8e]] – hPP2C β<br />
[[2cm1]] – PP2C + Mn – Micobacterium tuberculosis<br />
[[3d8k]] – PP2C – Toxoplasma gondii<br />
[[3jrq]], [[3kdj]], [[3nmn]] – AtPP2C + Pyl1 – Arabidopsis thaliana<br />
[[3nmt]], [[3kb3]], [[3nmv]], [[3ujl]] – AtPP2C + Pyl2<br />
[[4ds8]] – AtPP2C + Pyl3 + Mn<br />
[[3rt0]] – AtPP2C (mutant) + Pyl10<br />
[[3qn1]], [[3zvu]] – AtPP2C + Pyr1<br />
[[3ujg]] – AtPP2C + SNRK2<br />
[[3ujk]] – AtPP2C <br />


===PP5===
</StructureSection>


[[1s95]] – hPP5 catalytic domain <br />
== References ==
[[2g62]] – hPP5 <br />
<references/>
[[2bug]] – hPP5 tetratricopeptide domain + Hsp90 peptide<br />
[[3h60]] – hPP5 catalytic domain + Mn<br />
[[3h61]], [[3h62]], [[3h63]], [[3h64]] – hPP5 catalytic domain + Mn + inhibitor<br />
[[3h66]] – hPP5 catalytic domain + Zn <br />
[[3h67]], [[3h68]], [[3h69]] – hPP5 catalytic domain + Zn + inhibitor<br />
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 10:57, 23 July 2024

Function

Protein phosphatases (PP) or serine/threonine protein phosphatase regulate protein phosphorylation and thus are key in intracellular signal transduction processes.

  • PP1 is a serine/threonine phosphatase and is a key component of the insulin signaling pathway[1].
  • PP1C is the catalytic subunit of PP1.
  • PP1K is Mn+2/Mg+2-dependent PP1.
  • PP2A targets proteins in the oncogenic signaling pathways[2]. For PP2A see also HEAT Repeat.
  • PP2C are Mg/Mn-dependent and are essential for the regulation of cell cycle and stress signaling pathways. For details see
  • Protein Phosphatase 2C
  • ABA-regulated Protein Phosphatase 2C
  • ABA Signaling Pathway.
  • PP4 regulates a variety of cellular functions[3].
  • PP5 is activated by lipids and is involved in signal transduction[4].

Disease

Mutations in PP2A are found in many solid cancers and leukemias. PP2A-activating drugs are possible candidates for cancer therapeutics protocols[5]. Development of Alzheimer disease drugs could be based on restoration of PP2A activity[6].

Structural highlights

. Algal toxin binds at the surface pocket of the PP2A catalytic subunit which contains the Mn+2 ion cofactors[7]. Water molecule are shown as red sphere.

  • .
  • .

3D Structures of protein phosphatase

Protein phosphatase 3D structures


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

Drag the structure with the mouse to rotate

ReferencesReferences

  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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman, Alexsandra Tifane Santos do Nascimento
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Protein_phosphatase&oldid=4215766"