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Source ontology files for the Gene Ontology
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appropriate place(s) for "dehydroepiandrosterone sulfotransferase" synonym #15222

Open krchristie opened 6 years ago

krchristie commented 6 years ago

I was annotating PMID:1588921 (https://www.ncbi.nlm.nih.gov/pubmed/?term=1588921) and had a hard time identifying the appropriate function term for the enzyme named DHEA-ST and described as "capable of catalyzing the sulfation of DHEA" (DHEA stands for "dehydroepiandrosterone").

  1. If you search GO for "dehydroepiandrosterone sulfotransferase", you get only one term: "alcohol sulfotransferase activty" (GO:0004027) and the EXACT synonym in question has an EC reference of EC:2.8.2.2. However, the ENZYME page for the EC number EC:2.8.2.2 (https://enzyme.expasy.org/EC/2.8.2.2) doesn't mention dehydroepiandrosterone at all.

  2. If you search GO for "DHEA", you get this term: "steroid sulfotransferase activity" (GO:0050294) (with the EC xref of EC:2.8.2.15; https://enzyme.expasy.org/EC/2.8.2.15) due to this database_cross_reference from Reactome describing the reaction indicated in the paper being annotated:

Reactome:REACT_6969 dehydroepiandrosterone (DHEA) + PAPS => DHEA sulfate + PAP, Homo sapiens

  1. The UniProt entry for Q06520 (ST2A1_HUMAN) is the enzyme which is called DHEA-ST and its page lists this info:

Protein names:

  • Recommended name: Bile salt sulfotransferase (EC:2.8.2.14)
  • Alternative name(s):Dehydroepiandrosterone sulfotransferase
  • Short name: DHEA-ST

The EC# 2.8.2.14 is associated with the MF term bile-salt sulfotransferase activity (GO:0047704)

However, the EC page for EC 2.8.2.14 (https://enzyme.expasy.org/EC/2.8.2.14) has these interesting comments:

@deustp01 & @hdrabkin - Can you help me make sense of this. Currently, I have selected the term for "bile-salt sulfotransferase activity" for my annotation since this is consistent with both the UniProt page for the gene linked to the reference and the description of substrates on the ENZYME page for EC:2.8.2.14 (https://enzyme.expasy.org/EC/2.8.2.14) DOES list dehydroepiandrosterone sulfotransferase as a substrate.

I am wondering if the synonym "dehydroepiandrosterone sulfotransferase" should be removed from "alcohol sulfotransferase activty" (GO:0004027) or just changed from EXACT to BROAD, and also if this synonym should be added to "steroid sulfotransferase activity" (GO:0050294) and/or bile-salt sulfotransferase activity (GO:0047704)

ValWood commented 3 years ago

pinging @deustp01 & @hdrabkin

pgaudet commented 2 years ago

@kaxelsen Maybe you can help with this?

kaxelsen commented 2 years ago

The activity is shown in pmid:2764897 and is linked to Q06520 (ST2A1_HUMAN) . We do not yet have the reactions in Rhea, but I will create them when I have the time. dehydroepiandrosterone is not a bile-salt, so it should be linked to EC 2.8.2.2.

hdrabkin commented 2 years ago

I don't see how dehydroepiandrosterone sulfotransferase" could be a synonym of alcohol sulfotransferase activity" (GO:0004027) . Actually most of the synonyms there could be considered more like some sort of substrate specific terms for the def 3'-phosphoadenosine 5'-phosphosulfate + an alcohol = adenosine 3',5'-bisphosphate + an alkyl sulfate. RHEA currently maps 3 reactions to the EC:2.8.2.2 At best 'related'?

Et ec, only 'Hydroxysteroid sulfotransferase.' is listed as an alternative name. The EC xrefs for all of the rest of the GO 'synonyms ' might need to be removed.

RHEA:59304 3'-phosphoadenylyl sulfate + firefly L-luciferin = adenosine 3',5'-bisphosphate + firefly L-sulfoluciferin + H+ RHEA:59300 3'-phosphoadenylyl sulfate + firefly D-luciferin = adenosine 3',5'-bisphosphate + firefly D-sulfoluciferin + H+ RHEA:52368 3'-phosphoadenylyl sulfate + cholesterol = adenosine 3',5'-bisphosphate + cholesterol sulfate + H+

kaxelsen commented 2 years ago

A hydroxy group is an alcohol, and there is a hydroxy group on C3 of dehydroepiandrosterone, see https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28689. Following the ontology upwards brings you to "is a secondary alcohol (CHEBI:35681)"

So a reaction created with dehydroepiandrosterone as substrate will be a child of RHEA:22552 3'-phosphoadenylyl sulfate + an alcohol = adenosine 3',5'-bisphosphate + an alkyl sulfate + H+

hdrabkin commented 2 years ago

yes, I agree that hydroxysteroid sulfotransferase is a type of an alcohol sulfotransferase, but I'm not comfortable using it as as synonym.

pgaudet commented 2 years ago

The comment in EC:2.8.2.2 mentions that "Primary and secondary alcohols, including aliphatic alcohols, ascorbate, chloramphenicol, ephedrine and hydroxysteroids", so I suggest we add this comment and perhaps the other activites as 'narrowMatch'?

kaxelsen commented 2 years ago

Note that child relations in Rhea do not have anything to do with EC numbers. Relations in Rhea only looks at the chemistry, and in the chemical sense the substrates cholesterol and firefly luciferin are alcohols. Perhaps the error is to use Rhea child reactions as synonyms for the GO term.

kaxelsen commented 2 years ago

The activity is shown in pmid:2764897 and is linked to Q06520 (ST2A1_HUMAN) . We do not yet have the reactions in Rhea, but I will create them when I have the time. dehydroepiandrosterone is not a bile-salt, so it should be linked to EC 2.8.2.2.

I have now had time to look at the reaction. It turns out I was wrong. The reaction is RHEA:51216 3'-phosphoadenylyl sulfate + 3β-hydroxyandrost-5-en-17-one = 3β-sulfooxy-androst-5-en-17-one + adenosine 3',5'-bisphosphate + H+ 3β-hydroxyandrost-5-en-17-one = dehydroepiandrosterone

We are working on the relationships. Currently RHEA:22552 produces "an alkyl sulfate", which does not quite fit steroids, but we are working on an update of RHEA:22552 to be more inclusive, so soon RHEA:5121 might become is-a RHEA:22552

ValWood commented 5 days ago

@pgaudet will the Rhea mapping make this ticket out of date?