geneontology / go-ontology

Source ontology files for the Gene Ontology
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phosphoprotein phosphatase question #20587

Open ValWood opened 3 years ago

ValWood commented 3 years ago

GO:0004647 phosphoserine phosphatase activity I have one annotation to this, and the rest to the sibling GO:0004722 protein serine/threonine phosphatase activity

(so it is the same as the serine kinase vs serine/threonine protein kinase issue)

pgaudet commented 3 years ago

Note that there is also

alanbridge commented 3 years ago

Hi Pascale,

there seem to be rheas for each of these GOs

L - https://www.rhea-db.org/rhea/21208 D - https://www.rhea-db.org/rhea/24873

both linked to EC 3.1.3.3 Phosphoserine phosphatase, which seems to be capable of either, see https://www.qmul.ac.uk/sbcs/iubmb/enzyme/EC3/1/3/3.html. Note this is for free amino acids and not residues in proteins.

All the best, Alan

pgaudet commented 3 years ago

Thanks @alanbridge

There is some inconsistency - those are linked to https://enzyme.expasy.org/EC/3.1.3.3 that links to some protein phosphatases, such as P60487 (maybe only the 'PLPP's' are wrong? Who could check that ? )

It's also surprising that
L - https://www.rhea-db.org/rhea/21208 D - https://www.rhea-db.org/rhea/24873 have the same number of associations to UniProt entries - does that mean that the enzymes are non-specific ?

Thanks, Pascale

alanbridge commented 3 years ago

I guess the numbers are identical as this is a set of Rhea annotations based originally on EC numbers and the mapping to them - pinging @morgat and @kaxelsen who might be able to expound further.

pgaudet commented 3 years ago

@ValWood GO:0004647 phosphoserine phosphatase activity should NOT be used to annotate proteins, but only free amino acids.

alanbridge commented 3 years ago

@lbreuza could you please check the EC number / Rhea on PLPP? Perhaps should be EC 3.1.3.16 Protein-serine/threonine phosphatase and the Rheas that go with that (involving aa residues in proteins not free amino acids)

ValWood commented 3 years ago

Got it!

pgaudet commented 3 years ago

I changed the definition and added a comment to make it clearer taht we are talking about free amino acids and not phosphoproteins:

Catalysis of the reaction: L(or D)-O-phosphoserine + H2O = L(or D)-serine + phosphate, on a free amino acid." [PMID:9188776] +comment: Do not confuse with protein phosphatases. For protein phosphatases, consider GO:0004722 ; protein serine/threonine phosphatase activity or GO:0008138 ; protein tyrosine/serine/threonine phosphatase activity.

Thanks, Pascale

pgaudet commented 3 years ago

@lbreuza I cannot find evidence for any enzyme with GO:0036425 D-phosphoserine phosphatase activity- can you ?

If not I will merge the triad into the L-serine phosphatase.

Thanks, Pascale

alanbridge commented 3 years ago

Why not leave the D-specific term for the time being? There is old literature (I don't have time to go into now) on D-phosphoserine functions and regulation like https://pubmed.ncbi.nlm.nih.gov/8858931/

e.g.

D-Serine is a stereospecific agonist of the NMDA-associated glycine receptor

phosphoserine phosphatase may be an important enzyme in regulating the steady-state levels of D-serine in neocortical synaptosomes.

So there may be a specific need to capture it.

Cheers, Alan

pgaudet commented 3 years ago

OK, sure, just there seems to be no phosphatase. We can leave it.

lbreuza commented 3 years ago

Hi, I am updating P60487 and there are a few papers to check. Will check the other aspects.

lbreuza commented 3 years ago

Thanks @alanbridge

There is some inconsistency - those are linked to https://enzyme.expasy.org/EC/3.1.3.3 that links to some protein phosphatases, such as P60487 (maybe only the 'PLPP's' are wrong? Who could check that ? )

It's also surprising that L - https://www.rhea-db.org/rhea/21208 D - https://www.rhea-db.org/rhea/24873 have the same number of associations to UniProt entries - does that mean that the enzymes are non-specific ?

Thanks, Pascale

Hi, @pgaudet, I updated PDXP UniProtKB/Q96GD0 and orthologs to remove EC 3.1.3.3 since I could not find evidence for such activity. On the other hand I added EC=3.1.3.16 since it has 2 activities: Pyridoxal phosphate phosphatase and possibly a protein serine phosphatase.

I also checked P78330, the other proteins with EC 3.1.3.3 and they are indeed phosphoserine phosphatases (GO:0004647 phosphoserine phosphatase activity). I believe the phospho-L-serine phosphatase activity is physiologically relevant but I could at least find a paper that shows it could acts also as a phospho-L-serine phosphatase and decided to keep that activity.

So now it should be consistent in UniProt.

Best, Lionel