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NTR: ATP-dependent peptidyl-prolyl cis-trans isomerase activity #21477

Open RLovering opened 3 years ago

RLovering commented 3 years ago

Please provide as much information as you can:

sjm41 commented 3 years ago

Hi Ruth Is this the same as GO:0003755 peptidyl-prolyl cis-trans isomerase activity (which already has EC:5.2.1.8 as an xref, and is RHEA:16237)? That said, I don't see the ATP-dependence mentioned in the GO/EC/Rhea descriptions. Steven.

RLovering commented 3 years ago

Hi Steven, actually this is a good point.

PTPA https://www.uniprot.org/uniprot/Q15257 one of the descriptions in UniProt is: Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg2+ (in vitro).

According to InterPro https://www.ebi.ac.uk/interpro/entry/InterPro/IPR004327/ PTPA has been suggested to play a role in the insertion of metals to the PP2A catalytic subunit (PP2Ac) active site, to act as a chaperone, and more recently, to have peptidyl prolyl cis/trans isomerase activity that specifically targets human PP2Ac [1, 2, 3, 4, 5, 6]. Together, PTPA and PP2A constitute an ATPase and it has been suggested that PTPA alters the relative specificity of PP2A from phosphoserine/phosphothreonine substrates to phosphotyrosine substrates in an ATP-hydrolysis-dependent manner.

PPP2CA (alias PP2A I hope) is a serine/threonine-protein phosphatase https://www.uniprot.org/uniprot/P67775 https://www.ebi.ac.uk/interpro/entry/InterPro/IPR006186/ OK so probably the isomerase does not require ATPase activity

https://pubmed.ncbi.nlm.nih.gov/16916641/ states The conserved surface patch and the deep pocket (of PTPA) are responsible for binding to PP2A and ATP, respectively. PTPA and PP2A A-C dimer together constitute a composite ATPase. PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity.

So I guess I should curate both proteins to: GO:1904949 ATPase complex

and then I need a ATPase child term for both to contribute to. I don't think GO:0004176 ATP-dependent peptidase activity is right for a phosphotyrosine phosphatase maybe I need the term ATP-dependent phosphatase activity?

But as PP2A confers the phosphatase activity but PTPA contributes to the ATPase activity should ATP-dependent phosphatase activity be associated with both?

Sorry this detail of biochemistry is beyond me and you have a lot of experience of annotating these

Any help appreciated

Best

Ruth

pgaudet commented 3 years ago

@amorgat @kaxelsen This is described as a 'new activity' in the paper cited in the initial comment (PMID:16380387).

A 2012 review by the same authors continue to support the idea that this is a PPIase (PMID:22443683), but I dont find exhaustive evidence. Moreover, both the human (Q15257) and the yeast (P40454) genes are annotated to EC:5.2.1.8 and RHEA:16237, ie a reaction that does not require ATP.

Is RHEA planning to create a new activity for this?

Thanks, Pascale

pgaudet commented 2 years ago

ping @amorgat @kaxelsen see question above

ValWood commented 1 month ago

@pgaudet should we close this if it isn't clear the this activity is ATP dependent (the UniProt comments don't mention this either, is seems to be both a phosphatase and an isomerase.