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Source ontology files for the Gene Ontology
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Protein methyltransferases #7649

Closed gocentral closed 9 years ago

gocentral commented 14 years ago

Hi,

Dr. Steven Clarke a protein methyltransferase expert at UCLA recently contacted us at SGD to give us a heads up in a paper that describes a new methyltransferase activity. I therefore requested a new term 'N-terminal protein N-methyltransferase activity' so we can annotate the function as described in PMID: 20481588. During this exchange he has noticed some potential problems with the ontology beneath protein methyltransferase activity (GO:8276).

He first noted that the term "protein-leucine O-methyltransferase activity" (GO: 18423), used in yeast to annotate PPM1 (an enzyme which catalyses O-methylation on the alpha carboxyl group of the C-terminal leucine residue of PP2A) is confusing since the side chain of leucine has no oxygen atoms and the oxygen atom of internal leucine residues in the peptide bond is not modified. Since modification occurs only at the oxygen atoms of the free alpha carboxyl group of a leucine residue at the C-terminus of the protein he proposed a term modification to "protein C-terminal leucine carboxyl O-methyltransferase activity" (GO: 18423), since this would be less ambiguous. Since this is an instance of a "C-terminal protein carboxyl methyltransferase activity" (GO:3880) he also feels that "protein-leucine O-methyltransferase activity" (GO: 18423) should have parentage through "C-terminal protein carboxyl methyltransferase activity" (GO:3880).

The term "C-terminal protein carboxyl methyltransferase activity" (GO:3880), is also currently misdefined. It is currently defined as "Catalysis of the transfer of a methyl group to the carbon atom of the C-terminal residue of a protein." He noted that the "C" does not refer to a carbon atom but is short for "carboxyl". He said that since it's generally understood that for carboxyl methylation, the methylation occurs on the oxygen atoms of the carboxyl groups and not the carbon atom. He suggested that this could be made clearer if the parent term name was changed to "C-terminal protein carboxyl O-methyltransferase activity" (GO:3880) (but see below) and then the child terms would make more sense. As a result of the way its defined, there is also currently a true path violation for the child term "protein-S-isoprenylcysteine O-methyltransferase activity" (GO:4671). For example, yeast Ste14, catalyses O-methylation on the alpha carboxyl group of the C-terminal farnesyl cysteine or the C-terminal geranylgeranylcysteine residue of a number of isoprenylated proteins. He suggested in this case that the term could be modified to "protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity" (GO:4671), again for clarity.

I think so far we have these proposed changes:

C-terminal protein carboxyl O-methyltransferase activity (GO:3880'; modify term name and redefine) ----- protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity (GO:4671; modify term name) ----- protein C-terminal leucine carboxyl O-methyltransferase activity" (GO:18423; modify term name)

However, he also commented on the term "protein L-isoaspartate (D-aspartate) O-methyltransferase" (GO:4719). He's stated that it is a "protein carboxyl methyltransferase" but not a "C-terminal protein carboxyl methyltransferase" in the usual sense. So it couldn't currently be an instance of the more general term "C-terminal protein carboxyl methyltransferase activity" (GO:3880). However, he suggests that if the parent term were broadened from "C-terminal protein carboxyl methyltransferase activity" (GO:3880) to "protein carboxyl methyltransferase", than the following could become child terms:

protein-leucine O-methyltransferase activity (GO:18423), protein-S-isoprenylcysteine O-methyltransferase activity (GO:4671) and protein L-isoaspartate (D-aspartate) O-methyltransferase (GO:4719), as well as protein-glutamate O-methyltransferase activity (GO:8983)

This last term is used to annotate the bacterial CheR protein that is involved in chemotaxis, since this enzyme is also not a C-terminal protein carboxyl O-methyltransferase, but is a protein carboxyl O-methyltransferase.

So with this we could summarize the following proposed changes:

protein carboxyl methyltransferase (GO:3880; broadened, renamed and redefined) ----- protein C-terminal leucine carboxyl O-methyltransferase activity" (GO:18423; modify term name and add parentage) ----- protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity (GO:4671; modify term name and retain parentage) ----- protein L-isoaspartate (D-aspartate) O-methyltransferase (GO:4719; add parentage) ----- protein-glutamate O-methyltransferase activity (GO:8983; add parentage)

As far as I can tell there would not be a major impact on current annotations to these terms as the upper level term would be merely broadened, and the child terms that methylate C-terminal residues the C-terminus. Dr. Clarke has been very helpful with this area of the ontology and am sure would be willing to comment further, as required.

Cheers, Rob

Reported by: rnash

Original Ticket: geneontology/ontology-requests/7431

gocentral commented 14 years ago

Instead of redefining the existing terms to broaden them (which would essentially make them into a different term), I added new terms and clarified the defs of existing terms. These are the changes I made:

Changed name of GO:0018423 from "protein-leucine O-methyltransferase activity" to "protein C-terminal leucine carboxyl O-methyltransferase activity"; old name added as synonym

Changed name of GO:0004671 from "protein-S-isoprenylcysteine O-methyltransferase activity" to "protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity"; old name added as synonym

Added term: protein carboxyl O-methyltransferase activity ; GO:0051998 def: Catalysis of the transfer of a methyl group to a carboxyl group on a protein. syn: protein carboxyl methyltransferase activity EXACT

Renamed / corrected def: protein C-terminal carboxyl O-methyltransferase activity ; GO:0003880 def: Catalysis of the transfer of a methyl group to the oxygen atom of a carboxyl group at the C-terminal of a protein.

This is what the ontology looks like in that area now:

GO:0008276 : protein methyltransferase activity [i] GO:0051998 : protein carboxyl O-methyltransferase activity NEW ---[i] GO:0003880 : protein C-terminal carboxyl O-methyltransferase activity ------[i] GO:0018423 : protein C-terminal leucine carboxyl O-methyltransferase activity ------[i] GO:0004671 : protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity ---[i] GO:0008983 : protein-glutamate O-methyltransferase activity ---[i] GO:0004719 : protein-L-isoaspartate (D-aspartate) O-methyltransferase activity

...

GO:0008171 : O-methyltransferase activity [i] GO:0010340 : carboxyl-O-methyltransferase activity ---[i] GO:0051998 : protein carboxyl O-methyltransferase activity ------[i] (etc.)

Original comment by: girlwithglasses

gocentral commented 14 years ago

Original comment by: girlwithglasses

gocentral commented 14 years ago

Thanks for making these changes. I'll ask Dr. Clarke to take a quick look to see if this addresses his concerns, although at first glance it seems to cover what we had discussed.

Cheers, Rob

Original comment by: rnash