xref issues on acyl-CoA hydrolase activity child terms about go-ontology

[kaxelsen]

@sjm41

• add RHEA:68184 here as a broad xref?? RHEA maps RHEA:68184 (no mention of ADP-dependency) to EC:3.1.2.19 ("ADP-dependent medium-chain-acyl-CoA hydrolase")
  (I guess the question is, are there ADP-independent medium-chain-acyl-CoA hydrolase activities?) Do you know @kaxelsen ?

No, I'm not very well into acyl-CoA hydrolases. Both EC 3.1.2.18 and EC 3.1.2.19 are defined based on pmid:2901416 describing "A novel type of short- and medium-chain acyl-CoA hydrolases in brown adipose tissue mitochondria", but only EC 3.1.2.19 has links to Swiss-Prot, and they are all 5 to enterobacteria

[sjm41]

Oops, just the two. I've edited the list above.

[sjm41]

@pgaudet I just noticed in the new tree I posted above that these two terms both have the same EC xref:
palmitoyl-CoA hydrolase activity (GO:0016290, EC:3.1.2.2, RHEA:16645)
myristoyl-CoA hydrolase activity (GO:0102991, EC:3.1.2.2, RHEA:40119)

The EC:3.1.2.2 entry says:
Accepted Name: palmitoyl-CoA hydrolase
Alt name: long-chain fatty-acyl-CoA hydrolase
Reaction: H2O + hexadecanoyl-CoA <=> CoA + H(+) + hexadecanoate
Comment: Also hydrolyzes CoA thioesters of other long-chain fatty acids.

So maybe we should obsolete GO:0016290 and GO:0102991, with 'replaced by' long-chain fatty acyl-CoA hydrolase activity (GO:0052816) and add EC:3.1.2.2 as xref to that term?

[pgaudet]

GO:0047379 ADP-dependent short-chain-acyl-CoA hydrolase activity >> replace by new term 'short-chain fatty acyl-CoA hydrolase activity'
GO:0047380 ADP-dependent medium-chain-acyl-CoA hydrolase activity >> replace by parent GO:0052815 medium-chain acyl-CoA hydrolase activity

[pgaudet]

Will do the last 2 obsoletions here: #26597

[pgaudet]

Hi @sjm41

Should we obsolete GO:0047380 (no annotations) and GO:0047379 (1 annotation, paper does not mention ADP).

There are reference cited in the BRENDA records:
https://pubmed.ncbi.nlm.nih.gov/2901416/
https://pubmed.ncbi.nlm.nih.gov/2570608/

but I cannot tell which genes these paper describe.

I propose we obsolete these for now and restore if needed.

Unless @kaxelsen has more evidence for this reaction?

[sjm41]

Hi @pgaudet

Happy to obsolete GO:0047380 (ADP-dependent medium-chain-acyl-CoA hydrolase activity) - we already have the more general parent term 'GO:0052815 medium-chain acyl-CoA hydrolase activity' (=RHEA:68184) in this case.

Not so sure about obsoleting GO:0047379 (ADP-dependent short-chain-acyl-CoA hydrolase activity) because we don't currently have a more general parent term 'short-chain acyl-CoA hydrolase activity' (=RHEA:68180) for this one. Seems like we should have that (to match the sister terms above), but maybe there's no evidence it exists, so we don't need it!

Would be good to get @kaxelsen's take.

[pgaudet]

We could create 'short chain' - looks like many terms need to be reclassified:

Also, in seems that base on its children, 'GO:0016289 CoA hydrolase activity' means the same as 'GO:0047617 acyl-CoA hydrolase activity'.

What do you think ?

[sjm41]

Right. 'GO:0016289 CoA hydrolase activity' says "Catalysis of the reaction: X-CoA + H2O = X + CoA; X may be any group.", but then 'X' is an acyl group in all the child terms.

That said, I see there are a couple of things to consider/fix:

1. GO:0047617 acyl-CoA hydrolase activity has def "Catalysis of the reaction: acyl-CoA + H2O = CoA + a carboxylate." But based on the xrefs (EC:3.1.2.20, RHEA:16781) and children, the name should be changed to "fatty acyl-CoA hydrolase activity" and the def should be "Catalysis of the reaction: a fatty acyl-CoA + H2O = a fatty acid + CoA + H+".

2. Then, I think 'GO:0016289 CoA hydrolase activity' could be renamed 'acyl-CoA hydrolase activity' with def "an acyl-CoA + H2O = a carboxylate + CoA + H+" with xref RHEA:70423

Talk later....

[pgaudet]

I only find
https://www.uniprot.org/uniprotkb/Q7NUH6/entry
which has an automatic annotation to EC 3.1.2.19 - but how did that get predicted?

Discussion with @sjm41 : we will obsolete and keep xrefs on the appropriate parent

[kaxelsen]

Sorry, you are right. It was not the EC number, but the reaction RHEA:68184 that was used in Swiss-Prot.

I only find
https://www.uniprot.org/uniprotkb/Q7NUH6/entry
which has an automatic annotation to EC 3.1.2.19 - but how did that get predicted?

It was already present in the EMBL nucleotide entry.

[sjm41]

Clarifying info from Lucila Aimo regarding acyl vs fatty acyl:

• RHEA:70423, the R represents any acyl chain, including fatty acyl chains
• RHEA:16781, the R represents a fatty acyl chain (a fatty acid is a carboxylic acid with an aliphatic chain). This reaction does not include phenyls, nor cholesteryl, nor acetyl, formyl or any acyl that is not a fatty acid.

In other words:

• If the R group on the acyl-CoA is an aliphatic chain (ie. a hydrocarbon chain with no rings), then the molecule is classed as a fatty acyl-coA.
• But if the R group contains a ring (e.g. phenylacetyl-CoA, RHEA:70427), or contains atoms other than H/C (e.g. malonyl-CoA, RHEA:40219), or has no carbons (e.g. formyl-CoA, RHEA:19741), or has only 1 carbon meaning there is no ‘chain' (acetyl-CoA, RHEA:20289) then it is not a fatty-acyl-CoA, though it is still an acyl-CoA.

Also:
RHEA:20888 3-hydroxy-2-methylpropanoyl-CoA + H2O = 3-hydroxy-2-methylpropanoate + CoA + H+
is being reclassified to have this more specific parent:
RHEA:68180 a short-chain fatty acyl-CoA + H2O = a short-chain fatty acid + CoA + H+

[sjm41]

Based on all discussion above, I believe this is what we are aiming for:

thiolester hydrolase activity (GO:0016790, EC:3.1.2.-)
    |__acyl-CoA hydrolase activity (GO:0016289, RHEA:70423)
           |__(S)-methylmalonyl-CoA hydrolase activity (GO:0047511, EC:3.1.2.17, RHEA:17345)
           |__1,4-dihydroxy-2-naphthoyl-CoA thioesterase activity (GO:0061522, EC:3.1.2.28, RHEA:26309)
           |__4-hydroxybenzoyl-CoA thioesterase activity (GO:0018739, EC:3.1.2.23, RHEA:11948
           |__acetoacetyl-CoA hydrolase activity (GO:0047603, EC:3.1.2.11, RHEA:15673)
           |__acetyl-CoA hydrolase activity (GO:0003986, EC:3.1.2.1, RHEA:20289)
           |__fatty acyl-CoA hydrolase activity (GO:0047617, EC:3.1.2.20, RHEA:16781)
           |   |__short-chain fatty acyl-CoA hydrolase activity (NTR, RHEA:68180, EC:3.1.2.18[NARROW])
           |       |__3-hydroxyisobutyryl-CoA hydrolase activity (GO:0003860, EC:3.1.2.4, RHEA:20888)
           |   |__long-chain fatty acyl-CoA hydrolase activity (GO:0052816, RHEA:67680)
           |       |__palmitoyl-CoA hydrolase activity (GO:0016290, EC:3.1.2.2, RHEA:16645)
           |       |__myristoyl-CoA hydrolase activity (GO:0102991, EC:3.1.2.2, RHEA:40119)
           |   |__medium-chain fatty acyl-CoA hydrolase activity (GO:0052815, RHEA:68184, EC:3.1.2.19[NARROW])
           |   |__very long-chain fatty acyl-CoA hydrolase activity (GO:0052817, RHEA:67072)
           |__choloyl-CoA hydrolase activity (GO:0033882, EC:3.1.2.27, RHEA:14541)
           |__hydroxymethylglutaryl-CoA hydrolase activity (GO:0047994, EC:3.1.2.5, RHEA:16305)
           |__phenylacetyl-CoA hydrolase activity (GO:0033880, EC:3.1.2.25, RHEA:15337)
           |__succinyl-CoA hydrolase activity (GO:0004778, EC:3.1.2.3, RHEA:11516)

So I think the remaining tasks are:

• obsolete GO:0047380
• obsolete GO:0047379
• change GO:0016289 name to "acyl-CoA hydrolase activity", add RHEA:70423 xref, update def to match RHEA
• add EC:3.1.2.28 and RHEA:26309 xrefs to GO:0061522
• change parent of GO:0003860 to NTR for "short-chain fatty acyl-CoA hydrolase activity"
• change GO:0047617 name to "fatty acyl-CoA hydrolase activity" and update def to match RHEA/EC
• make new term for "short-chain fatty acyl-CoA hydrolase activity" xrefs: RHEA:68180, EC:3.1.2.18[NARROW] , is_a GO:0047617
• change GO:0102991 parent to GO:0052816
• add EC:3.1.2.19 as NARROW xref to GO:0052815

@pgaudet I can do most of these tasks, and then leave the obsoletions and NTR to you. OK?

[pgaudet]

Sounds good!

[pgaudet]

Are there 2 or 3 terms to obsolete? you have GO:0047380 twice in the list.

[sjm41]

@pgaudet I've finished doing my edits, so assigning to you for the rest.
For some reason, I couldn't add RHEA:70423 xref to GO:0016289 "acyl-CoA hydrolase activity" - can you see if you can do that without getting an error?

[pgaudet]

+[Term]
+id: GO:0141126
+name: short-chain fatty acyl-CoA hydrolase activity
+namespace: molecular_function
+def: "Catalysis of the reaction: a small-chain fatty acyl-CoA + H2O = a medium-chain fatty acid + CoA + H+. A small-chain fatty acid has an aliphatic tail of less than 6 carbons." [RHEA:68180]
+comment: While there is not universal consensus on the lengths of short-, medium-, long- and very-long-chain fatty acids, the GO uses the definitions in ChEBI (see CHEBI:26666, CHEBI:59554, CHEBI:15904 and CHEBI:27283).
+xref: EC:3.1.2.18 {source="skos:relatedMatch"}
+xref: MetaCyc:3.1.2.18-RXN
+xref: RHEA:68180
+is_a: GO:0047617 ! fatty acyl-CoA hydrolase activity
+property_value: term_tracker_item "#26441" xsd:anyURI
+created_by: pg
+creation_date: 2023-12-08T09:05:55Z

[sjm41]

Thanks @pgaudet ! But can you change 'small' and 'medium' to 'short' in the def?
That is:
+def: "Catalysis of the reaction: a short-chain fatty acyl-CoA + H2O = a short-chain fatty acid + CoA + H+. A short-chain fatty acid has an aliphatic tail of less than 6 carbons." [RHEA:68180]

[pgaudet]

Also changed 'very-long-chain acyl-CoA dehydrogenase activity' to very-long-chain FATTY acyl-CoA dehydrogenase activity : isn't this right ?

[sjm41]

Yep. I just starting to look at the acyl-CoA dehydrogenase branch systematically to see if other similar changes are needed there (as done for acyl-CoA hydrolase branch here). So might be another ticket coming....

[pgaudet]

ah yes thanks! I am spreading out...

[sjm41]

Looks like I mistakingly made "3-hydroxyisobutyryl-CoA hydrolase activity (GO:0003860)" a child of "short-chain fatty acyl-CoA dehydrogenase activity (GO:0016937)" instead of the intended "short-chain fatty acyl-CoA hydrolase activity ( GO:0141126)".
I will fix this now.

[sjm41]

Also just noticed this outstanding task mentioned above:

For some reason, I couldn't add RHEA:70423 xref to GO:0016289 "acyl-CoA hydrolase activity" - can you see if you can do that without getting an error?

I'll try to do this again now.

[sjm41]

For some reason, I couldn't add RHEA:70423 xref to GO:0016289 "acyl-CoA hydrolase activity" - can you see if you can do that without getting an error?
I'll try to do this again now.

Nope, failed again. Here's the error:

FAIL Rule ../sparql/one-to-one-xrefs-by-subject-violation.sparql: 1 violation(s)
c,one_to_one_prefix
http://purl.obolibrary.org/obo/GO_0016289,RHEA:

@pgaudet Do you see what the issue is here??

[pgaudet]

No, this is really weird. I am trying here: #27911

[pgaudet]

Failed for mw as well (unsurprisingly!)

@balhoff Can you help us?

[balhoff]

The xrefs from the obsolete term GO:0047901 are being transferred to its replacement during the build. This causes the multiple xrefs error. This is a really confusing system, and I recently opened an issue to fix it: #27821

So the immediate solution is to modify the xrefs on GO:0047901.

[sjm41]

Aha, thanks @balhoff

@pgaudet All the term xrefs on this obsolete term should just be removed, right?

id: GO:0047901
name: obsolete formyl-CoA hydrolase activity
namespace: molecular_function
def: "OBSOLETE. Catalysis of the reaction: formyl-CoA + H2O = CoA + formate + H+." [EC:3.1.2.10, RHEA:19741]
comment: This term was obsoleted because the enzyme that catalyzes this reaction has not been identified.
synonym: "formyl coenzyme A hydrolase activity" RELATED [EC:3.1.2.10]
xref: EC:3.1.2.10
xref: KEGG_REACTION:R00521
xref: MetaCyc:FORMYL-COA-HYDROLASE-RXN
xref: RHEA:19741
property_value: term_tracker_item "#26443" xsd:anyURI
is_obsolete: true
replaced_by: GO:0016289

[sjm41]

Looked at the obsoletion doc.....

5. Cross-references
   Check if there are cross-references to Reactome, RHEA, EC, MetaCyc xref to the term. If there are, notify the various groups in the obsoletion email.
   These cross-references should be removed.
   There is no need to edit Reactome xrefs are imported automatically from a file supplied by Reactome.
   Definition cross-references to RHEA, EC, MetaCyc should be also be removed. Replace by GOC:curators if no reference is left.

So, I will go ahead and remove the term and def xrefs on GO:0047901, and then try re-adding RHEA:70423 xref to GO:0016289.

[sjm41]

Success!

id: GO:0016289
name: acyl-CoA hydrolase activity
namespace: molecular_function
def: "Catalysis of the reaction: an acyl-CoA + H2O = a carboxylate + CoA + H+." [RHEA:70423]
synonym: "CoA hydrolase activity" BROAD []
xref: RHEA:70423
is_a: GO:0016790 ! thiolester hydrolase activity
property_value: term_tracker_item "#26441" xsd:anyURI

id: GO:0047901
name: obsolete formyl-CoA hydrolase activity
namespace: molecular_function
def: "OBSOLETE. Catalysis of the reaction: formyl-CoA + H2O = CoA + formate + H+." [GOC:curators]
comment: This term was obsoleted because the enzyme that catalyzes this reaction has not been identified.
synonym: "formyl coenzyme A hydrolase activity" RELATED []
property_value: term_tracker_item "#26443" xsd:anyURI
is_obsolete: true
replaced_by: GO:0016289