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Source ontology files for the Gene Ontology
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Can add full EC to GO:0000810?? #9573

Closed gocentral closed 9 years ago

gocentral commented 12 years ago

Greetings. I believe that this reaction now has a full EC: 3.1.3.81

http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/1/3/81.html

But, I am not sure if you want to add this because in the enzyme comment, it implies that this EC number can only be used for enzymes that catalyze both this and the subsequent reaction that is currently attached to 3.1.3.4 in GO (GO:0008195).

Sincerely, kate

Reported by: kadreher

Original Ticket: geneontology/ontology-requests/9366

gocentral commented 12 years ago

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Hi Kate,

Thanks. I believe we'd want to represent each enzymatic activity separately. The comments in http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/1/3/81.html indicate that the enzyme is bifunctional, and that the two activities are quite distinct. The reaction shown in GO:0000810 looks like it is the sum of two separate reactions that are catalyzed by the two distinct enzymatic activities. GO already has GO:0008195 phosphatidate phosphatase activity that is defined as "Catalysis of the reaction: a 3-sn-phosphatidate + H2O = a 1,2-diacyl-sn-glycerol + phosphate." and has EC:3.1.3.4 as a Dbxref. Based on this and to conform to the EC entries, my suggestion would be:

a) GO:0000810 diacylglycerol pyrophosphate phosphatase activity:

b) GO:0008195 phosphatidate phosphatase activity: edit def. from "Catalysis of the reaction: a 3-sn-phosphatidate + H2O = a 1,2-diacyl-sn-glycerol + phosphate." to "Catalysis of the reaction: a 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate." (where a 1,2-diacylglycerol 3-phosphate = a 3-sn-phosphatidate, so the meaning of the term does not change.)

If this sounds good, I'll implement it. Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Hi Kate, I've now implemented the plan below, and I've submitted an annotation ticket to see if annotations can be added: https://sourceforge.net/tracker/?func=detail&aid=3517436&group\_id=36855&atid=605890 Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Hi Paola. I logged in and now I can add a comment

Original comment by: kadreher

gocentral commented 12 years ago

Original comment by: kadreher

gocentral commented 12 years ago

Hi Paola,

First, I apologize that my email before was so rushed and not written very politely! I'll reproduce an edited form of it here for the record:

Thank you for working on my request. 1) I am not sure why you said that the current version of GO:0000810 seems like it has a composite reaction: Catalysis of the reaction: a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacylglycerol-3-phosphate + phosphate.

This reaction seems to capture one of the two sequential reactions that are now part of EC 3.1.3.81. The second would be the reaction currently annotated at GO:0008195: "Catalysis of the reaction: a 3-sn-phosphatidate + H2O = 1,2-diacyl-sn-glycerol + phosphate."

I believe that the composite reaction would be: a 1,2-diacyl-sn-glycerol 3-diphosphate + 2H2O = a 1,2-diacylglycerol-3-phosphate + 2 phosphate.

I agree with the GO idea that each specific function should be uniquely represented, and I feel that this GO term should include the one-step reaction: a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacylglycerol-3-phosphate + phosphate

But, I'm still a bit wary of putting the 3.1.3.81 EC number now because that should probably either mention the composite reaction in the definition or show both sequential reactions.

Is there anyway to have a dbxref that is sort of like the "related" synonym class? Should the definition point out that many enzymes that have this activity also catalyze the second step defined by GO: GO:0008195 so that curators are aware that they should add this one, too? Would it be possible to put a textual note about 3.1.3.81 as a "related" EC while explaining that it technically refers to an enzyme that can do both reactions?

On a more practical note, I believe that the "a" should remain in the definition for GO:0000810

a 1,2-diacyl-sn-glycerol 3-diphosphate + H2O = a 1,2-diacylglycerol-3-phosphate + phosphate.

There are many combinations of acyl chains of varying lengths and desaturations, etc., that can form these diacylglycerols, so indicating that this reaction refers to all members of that class of compounds, using an "a" sounds more appropriate to me.

But, by that same logic, I agree that adding "a" to the definition for GO:0008195:

"Catalysis of the reaction: a 1,2-diacylglycerol 3-phosphate + H2O = a 1,2-diacyl-sn-glycerol + phosphate."

I also like your following proposed modifications:

I look forward to your feedback.

Thank you!

Original comment by: kadreher

gocentral commented 12 years ago

Hi Kate,

I can certainly add the "a"s in the definitions (I see your point, thanks for explaining), and I will also add a definition comment to point curators to GO:0008195 as well.

As for the reactions to be specified in each of the two GO terms GO:0000810 and GO:0008195, to recap: we agree that each GO term should indicate a single enzymatic activity (reaction) of the ones that are carried out by an enzyme (so if the enzyme is bifunctional, we want two GO activity terms, regardless of how many EC numbers the enzyme was given); however, if an enzyme reaction is multi-step, but with just one EC number, because the multi-step reaction is carried out by a single enzymatic activity, we want to add one GO term for the overall reaction, and add a comment to say the reaction is multi-step (and whether one of the steps is spontaneous).

I am now a bit confused about the overall situation in this case, so it would speed the resolution up a lot if you could please (re)suggest, based on the above, what the exact name and definition should be for GO:0000810 and GO:0008195. If it is necessary to add a GO term to comply with the strategy above, this can certainly be done.

Thanks for your help, Paola

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Hi Paola,

Unfortunately, I think that I am now confused as well! I am not sure what is meant by: the multi-step reaction is carried out by a single enzymatic activity, we want to add one GO term for the overall reaction, and add a comment to say the reaction is multi-step (and whether one of the steps is spontaneous). . . .

I will try to investigate this more using the following publications: http://www.jbc.org/content/271/4/1868.full.pdf+html http://www.jbc.org/content/228/2/915.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/9603941

Sincerely, kate

Original comment by: kadreher

gocentral commented 12 years ago

Summary: Following email exchange with Kate, I have edited GO:0000810 and GO:0008195 so they reflect current information for EC 3.1.3.81 and 3.1.3.4 (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/1/3/81.html and http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/1/3/4.html). The enzyme entry for 3.1.3.81 states that this is a bifunctional enzyme, but I can't find enough details (i.e. precise reactions) to be able to split it into two GO terms. I've indicated this in a definition comment. Since the enzyme entry also states that "The phosphatase activity of the bifunctional enzyme ... is distinct from ... enzyme EC 3.1.3.4", I've withdrawn my annotation ticket.
Thanks, Paola

Original comment by: paolaroncaglia

gocentral commented 12 years ago

Original comment by: paolaroncaglia