search

geneontology / go-ontology

Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
Creative Commons Attribution 4.0 International
222 stars 40 forks source link

query GO:0052928 CTP:3'-cytidine-tRNA cytidylyltransferase activity #11721

Closed gocentral closed 2 years ago

gocentral commented 9 years ago

I am trying to figure the differenece between these:

GO:0052928 CTP:3'-cytidine-tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA with a 3' cytidine + CTP = a tRNA with a 3' CC end + diphosphate.

GO:0052927 CTP:tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA precursor + CTP = a tRNA with a 3' cytidine end + diphosphate.

the genes i am annotating seem to be annotated to both and they have identical EC number. What is a CC end?

val

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/11552

gocentral commented 9 years ago

Seems to come directly from KEGG

http://www.genome.jp/dbget-bin/www_bget?rn:R09384 http://www.genome.jp/dbget-bin/www_bget?rn:R09383

Original comment by: dosumis

gocentral commented 9 years ago

The GONUTS page for GO:0052928 (http://gowiki.tamu.edu/wiki/index.php/Category:GO:0052928_!_CTP:3%27-cytidine-tRNA_cytidylyltransferase_activity) and its ExPASY ENZYME link look like they might be helpful here, hinting at a description of CC and also at a possible history of EC term merger (so the two GO terms could possibly point to two activities that are now regarded as one by the enzymologists).

Original comment by: deustp01

gocentral commented 9 years ago

Interesting that the EC term def at http://enzyme.expasy.org/EC/2.7.7.72 has a different reaction to either of the above:

A tRNA precursor + 2 CTP + ATP <=> a tRNA with a 3' CCA end + 3 diphosphate

This page also has a nice description: The CCA sequence is added to the tRNA precursor by stepwise nucleotide addition performed by a single enzyme that is ubiquitous in all living organisms. Although the enzyme has the option of releasing the product after each addition, it prefers to stay bound to the product and proceed with the next addition.

It also mentions EC mergers: Formerly EC 2.7.7.21 and EC 2.7.7.25.

Tracing original IDs: http://www.genome.jp/dbget-bin/www_bget?ec:2.7.7.25 http://www.genome.jp/dbget-bin/www_bget?ec:2.7.7.21

The old names look consistent with the original entries being for separate enzymes adding CC and adding A, being merged to one activity which adds CCA.

This KEGG page seems to allow for both substrates: http://www.genome.jp/dbget-bin/www_bget?ec:2.7.7.72 :

Substrate
tRNA precursor [CPD:C02211]; CTP [CPD:C00063]; ATP [CPD:C00002]; tRNA with a 3' cytidine [CPD:C19078]; tRNA with a 3' CC end [CPD:C19080] Product tRNA with a 3' CCA end [CPD:C19085]; diphosphate [CPD:C00013]; tRNA with a 3' cytidine end; tRNA with a 3' CC end [CPD:C19080]

This is consistent with tRNA with a 3' CC end [CPD:C19080] as an intermediate that is sometimes release.

So, I think you're right that these should be merged.

Original comment by: dosumis

gocentral commented 9 years ago

Looks like these two should be merged too:

id "GO:0004810"^^string label "tRNA adenylyltransferase activity"^^string comment "This term represents a deleted EC activity and is scheduled for obsoletion."^^string database_cross_reference "EC:2.7.7.25"^^string

id "GO:0052929"^^string label "ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity"^^string database_cross_reference "EC:2.7.7.72"^^string database_cross_reference "KEGG:R09386"^^string definition "Catalysis of the reaction: a tRNA with a 3' CC end + ATP = a tRNA with a 3' CCA end + diphosphate."^^string

I guess it doesn't really matter which term wins in the merge so I'll chose the one with most annotations to reduce churn. The new term will take its definition from the Expasy page. Does that seem reasonable?

Original comment by: dosumis

gocentral commented 9 years ago

Sounds reasonable to me. See what Peter thinks.

val

Original comment by: ValWood

gocentral commented 9 years ago

Sounds reasonable to me too. Peter

Original comment by: deustp01

gocentral commented 9 years ago

One might want to look at:PMID:18523015 Evolution of tRNA nucleotidyltransferases: a small deletion generated CC-adding enzymes. " In some organisms, CCA synthesis is accomplished by the collaboration of evolutionary closely related enzymes with partial activities (CC and A addition). These enzymes carry all known motifs of the catalytic core found in CCA-adding enzymes. Therefore, it is a mystery why these polymerases are restricted in their activity and do not synthesize a complete CCA terminus. "

In some organisms ONE enzyme can add the whole CCA; In some bacteria, however, it appears TWO enzymes, one to add CC, a separate one to add the final A. Also note that in eukaryotes, CCA is not encoded and always has to be added after removal of 3' trailer, but in bacteria, CCA is encoded; 3' end maturation stops at the CCA. However, bacteria still do have CCA adding enzymes to maintain the CCA

Original comment by: hdrabkin

gocentral commented 9 years ago

Hi Harold, Okay, in different reactions different units get added to the 3' end of the tRNA. But if it's mechanistically the same reaction, then couldn't a single GO molecular function term could cover all the reactions? Peter

Original comment by: deustp01

gocentral commented 9 years ago

Thanks Harold. So I guess we need 3 terms. Do these look OK?

CCA tRNA nucleotidyltransferase activity (<- new?) A tRNA precursor + 2 CTP + ATP <=> a tRNA with a 3' CCA end + 3 diphosphate

ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity Catalysis of the reaction: a tRNA with a 3' CC end + ATP = a tRNA with a 3' CCA end + diphosphate

CTP:3'-cytidine-tRNA cytidylyltransferase activity O:0052927 CTP:tRNA cytidylyltransferase activity A tRNA precursor + 2 CTP <=> a tRNA with a 3' CC end + 2 diphosphate

This makes retrofitting annotations tricky. From the sound it, this could potentially be automated based on species.

Original comment by: dosumis

gocentral commented 9 years ago

It appears the might have gotten split out tRNA + CTP -> tRNA-C Then CTP + tRNA-C -> tRNA-CC then tRNA-CC + ATP -> tRNA-CCA In some organisms one enzyme does steps 1-3, even though we know it is sequencial (ie, CCA is not made first and then added).

I just want to make sure that there is not a separate enzyme for rxn1 vs 2.(contacting my expert now), so that in some organsims it is 1+2 (again, sequentially).

Original comment by: hdrabkin

gocentral commented 9 years ago

Some cross-posting confusion going on here. Looking at paper more carefully.

Original comment by: dosumis

gocentral commented 9 years ago

Yes, I just want to be sure that there is NOT a case that JUST the C is added. It's just because I am wondering why this one was made to begin with GO:0052927 CTP:tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA precursor + CTP = a tRNA with a 3' cytidine end + diphosphate.

Original comment by: hdrabkin

gocentral commented 9 years ago

But if it's mechanistically the same reaction, then couldn't a single GO molecular function term could cover all the reactions?

That would certainly be easier for us.

Harold: Perhaps more efficient for you to take the ticket, given that you're getting some expert input?

Cheers, David

Original comment by: dosumis

gocentral commented 9 years ago

Peter: minimally two are needed. If we only had one to encompass all three, then there could be annotation error if someone were annotating the two enzymes that only add CC and only add the A. Only in eukaryotes would it be ok to say one enzyme did C1, C2, and then A1.

Original comment by: hdrabkin

ValWood commented 7 years ago

This looks close to a solution? Also, related to this ticket? https://github.com/geneontology/go-ontology/issues/11996

ValWood commented 7 years ago

It sounds like a resolution was reached but never implemented.

hdrabkin commented 7 years ago

Final (I hope comments) My expert never got back to me ( on: CCA tRNA nucleotidyltransferase activity (<- new?) A tRNA precursor + 2 CTP + ATP <=> a tRNA with a 3' CCA end + 3 diphosphate Each C is added separately, as is the A once the C's are added. THis proposed term seems more like a summary of the entire process (and note in some cases, two different enzymes are needed). SO I would feel uncomfortable making this activity term.

ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity Catalysis of the reaction: a tRNA with a 3' CC end + ATP = a tRNA with a 3' CCA end + diphosphate This would appear to be GO:0004810

CTP:3'-cytidine-tRNA cytidylyltransferase activity GO:0052927 CTP:tRNA cytidylyltransferase activity A tRNA precursor + 2 CTP <=> a tRNA with a 3' CC end + 2 diphosphate Again, these are done in two steps, so I'm wondering if

ValWood commented 7 years ago

So is no action required here?

I still don't understand the difference between these 2 terms

I have 2 GPs and both are annotated to both? They have the same EC number

GO:0052928 CTP:3'-cytidine-tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA with a 3' cytidine + CTP = a tRNA with a 3' CC end + diphosphate.

GO:0052927 CTP:tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA precursor + CTP = a tRNA with a 3' cytidine end + diphosphate.

See original comment.

So merge or close (If closed I'll assume based on the EC that our annotation is OK and remain confused....)

ValWood commented 7 years ago

Or parent child, are they responsibly for sucessive additions and one is a specific reaction?

hdrabkin commented 7 years ago

If my expert can't find a case for a separate gene product for the two CTP transferases, I'm inclined to merge. I also see I need to merge the two ATP transferase terms, which I should have done this morning.

hdrabkin commented 7 years ago

Still waiting; shouldn't be too long.

hdrabkin commented 6 years ago

My expert got back to me To his knowledge, there is no case where an just adds the first C. It's always two consecutive Cs so GO:0052928 CTP:3'-cytidine-tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA with a 3' cytidine + CTP = a tRNA with a 3' CC end + diphosphate. GO:0052927 CTP:tRNA cytidylyltransferase activity Catalysis of the reaction: a tRNA precursor + CTP = a tRNA with a 3' cytidine end + diphosphate. 927 will be the base, and will merge 928 into it. Def would be Catalysis of the reaction: a tRNA precursor + 2CTP = a tRNA with a 2 addtiional cytidine residues + 2 diphosphate.

hdrabkin commented 6 years ago

Ok, now I see various and sundry problems here which might require an annotation review. There are 3 types of enzymes involved here

  1. CCA tRNA nucleotidyltransferase. adds CCA consecutively, but can also add A to a 3' CC. THIS is the activity that should be annotated to for most organisms. This is EC:2.7.7.72, CCA tRNA nucleotidyltransferase. Even if all that is measured is "A" addition, this is the enzyme that does in

  2. in SOME organisms, the CC gets added by one enzyme and the A gets added by a second enzyme. In Aquifex aeolicus, Deinococcus radiodurans, Bacillus halodurans, and Synechocystis sp., CCA synthesis is catalyzed by two nucleotidyltransferases (CC-adding and A-adding enzyme) in a stepwise addition of two C and one A residues.

This also means that the reaction in GO indicating addition of a single A to the 3'end of a tRNA-CC should only be used for cases like #2.

hdrabkin commented 6 years ago

Bottom line is that I think an annotation review might be in order.

hdrabkin commented 6 years ago

GO:005292 ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity; should be used only for case 2 GO:0052928 CTP:3'-cytidine-tRNA cytidylyltransferase activity; should not be used; should be obsoleted

GO:0052927: CTP:tRNA cytidylyltransferase activity; case 2 only, different gene product It's def Catalysis of the reaction: a tRNA precursor + CTP = a tRNA with a 3' cytidine end + diphosphate., should be changed to Catalysis of the reaction: a tRNA precursor + 2CTP = a tRNA with a 3' CC end

GO:0001680 tRNA 3'-terminal CCA addition This is EC 2.7.7.72 ; this can added either the C's or the As as needed. This is what all other organisms should be annotated to.

hdrabkin commented 6 years ago

OR, since I don't see any annotations properly attributed to 927 and 292, I could merge those into 1680 and all current annotations would be correct.

also found "GO:0004810, which should be merged into GO:0001680 (tRNA adenylyltransferase activity) ; both have same ec number even, so this was NEVER meant to be an enzyme that only adds A (also represents an deprecated EC number and is scheduled to be obsoleted anyways

ValWood commented 6 years ago

Do the merge ;)

v

ValWood commented 4 years ago

Hi Harold, any closure on this one?

hdrabkin commented 4 years ago

Even RHEA uses a single id (does not break out the steps RHEA:14433 the EC 2.7.7.72) However, if we wanted to annotate quifex aeolicus, Deinococcus radiodurans, Bacillus halodurans, and Synechocystis sp., CCA synthesis is catalyzed by two nucleotidyltransferases (CC-adding and A-adding enzyme) we DO need a CC synthesis term for one enzyme and an A term for the other.

hdrabkin commented 3 years ago

Preparing for the merge d: GO:0004810 name: tRNA adenylyltransferase activity def: "Catalysis of the reaction: ATP + tRNA(n) = diphosphate + tRNA(n+1)." [EC:2.7.7.25] comment: This term represents a deleted EC activity and is scheduled for obsoletion. xref: EC:2.7.7.25 => this is a grouping term in GO, remove EC, remove comment

This should actually be merged but there is a problem (there is a ticket on this already).

19854, #17855, and #11721

  1. in most annotations, one monitors the enzyme activity using only the A- addition, but the enzyme is still the CCA addition enzyme. Some use CTP also.
  2. However, although most organisms have ONE enzyme, there are some that have two separate enzymes, one to add the CC, and a separate to add the A. (PMID:18523015) So I was going to merge all of them to just CCA, BUT, needed to know if ANY of the existing annotations were to the organisms using the two enzymes.

Note: RHEA does not break out the CCA into 3 reactions (much like they do not split out each of the AARs into two reactions, A; creation of the aa-amp, and B: transfer from aa-amp to aa-tRNA (one can measure both reactions). So, we actually need.

  1. term for the CCA enzyme; term merge for most of these
  2. a separate CC term
  3. a separate A term; 2 and 3 need a taxon restriction to only those organisms that process the tRNA 3' end with 2 separate enzyme.

I will also copy this to the other tickets.

pgaudet commented 2 years ago

There are 2 related RHEAs: https://www.rhea-db.org/rhea/60012 (no EC): a tRNA with a 3' CC end + ATP = a tRNA with a 3' CCA end + diphosphate - I think this represents the 'A' only reaction you describe above and https://www.rhea-db.org/rhea/14433 (EC:2.7.7.72) : a tRNA precursor + ATP + 2 CTP = a tRNA with a 3' CCA end + 3 diphosphate

hdrabkin commented 2 years ago

These are rectified in ticket #19854, so will close this one now.