Should GO:0033842 be a child of GO:0033207?

[sjm41]

Seems like "N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase activity" (GO:0033842) should be a child of "beta-1,4-N-acetylgalactosaminyltransferase activity" (GO:0033207)?

==
[Term]
id: GO:0033842
name: N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase activity
namespace: molecular_function
def: "Catalysis of the reaction: UDP-N-acetyl-D-galactosamine + N-acetyl-beta-D-glucosaminyl group = UDP + N-acetyl-beta-D-galactosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl group." [EC:2.4.1.244]
synonym: "beta1,4-N-acetylgalactosaminyltransferase activity" EXACT [EC:2.4.1.244]
synonym: "beta1,4-N-acetylgalactosaminyltransferase III activity" EXACT [EC:2.4.1.244]
synonym: "beta1,4-N-acetylgalactosaminyltransferase IV activity" EXACT [EC:2.4.1.244]
synonym: "beta4GalNAc-T3" RELATED [EC:2.4.1.244]
synonym: "beta4GalNAc-T4" RELATED [EC:2.4.1.244]
synonym: "UDP-N-acetyl-D-galactosamine:N-acetyl-D-glucosaminyl-group beta-1,4-N-acetylgalactosaminyltransferase activity" EXACT [EC:2.4.1.244]
xref: EC:2.4.1.244
xref: MetaCyc:2.4.1.244-RXN
xref: RHEA:20493
is_a: GO:0008376 ! acetylgalactosaminyltransferase activity
is_a: GO:0140103 ! catalytic activity, acting on a glycoprotein

==
[Term]
id: GO:0033207
name: beta-1,4-N-acetylgalactosaminyltransferase activity
namespace: molecular_function
def: "Catalysis of the transfer of an N-acetylgalactosaminyl residue from UDP-N-acetyl-galactosamine to an acceptor molecule, forming a beta-1,4 linkage." [GOC:mah]
synonym: "beta-1,4-GalNAc transferase activity" EXACT []
is_a: GO:0008376 ! acetylgalactosaminyltransferase activity

[sjm41]

Hi Harold - any thoughts/insights on this?

[hdrabkin]

@deustp01 what do you think?

[hdrabkin]

I notice id: GO:0033207 really has no decent references (like many of the grouping terms)

[hdrabkin]

I'm inclined to agree

[deustp01]

The chemistry here is way beyond my limited knowledge of glycoprotein biochemistry. Sorry!

[pgaudet]

Merge ?
https://enzyme.expasy.org/EC/2.4.1.244

Accepted Name: N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N- acetylgalactosaminyltransferase.
synonym: Beta-1,4-N-acetylgalactosaminyltransferase.

GO:0033207 name: beta-1,4-N-acetylgalactosaminyltransferase activity

Pascale

[pgaudet]

Some proteins are annotated to all 3

https://www.uniprot.org/uniprot/Q9VAQ8
(mapped to EC:2.4.1.244)

acetylgalactosaminyltransferase activity Source: FlyBase
beta-1,4-N-acetylgalactosaminyltransferase activity Source: FlyBase
N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase activity Source: FlyBase

[sjm41]

Reviewing this again, I agree with Pascale - we should merge GO:0033842 and GO:0033207.

Looking at QuickGO, I see 470 annotations to GO:0033842 and only 39 annotations to GO:0033207.
Of those 39 annotations using GO:0033207:

• 3 IDA annotations from FlyBase
• 1 IDA annotation from WormBase
• 35 IEA annotations from EnsemblMetazoa (based on the IDA FB/WB source annotations)

Looking at the three IDAs from FB (which correspond to just two genes):
UniProtKB:Q7KN92 beta4GalNAcTA PMID:17498683
UniProtKB:Q86NU9 beta4GalNAcTB PMID:17498683
UniProtKB:Q9VAQ8 beta4GalNAcTB PMID:17498683
I can say that the merge of the two GO terms would be fine.

@vanaukenk - can you check out the WB annotation using GO:0033207 to Q9GUM2?

==

Some proteins are annotated to all 3
https://www.uniprot.org/uniprot/Q9VAQ8
(mapped to EC:2.4.1.244)
acetylgalactosaminyltransferase activity Source: FlyBase
beta-1,4-N-acetylgalactosaminyltransferase activity Source: FlyBase
N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase activity Source: FlyBase

Yeah, that's what got me looking at the two GO terms in the first place!
The first annotation (to the parent term from PMID:15563714) appears to be correct, based on the description of the assay in that paper.

[sjm41]

Oh, hang on....
I see that GO:0033842, but not GO:0033207, currently has parent of "catalytic activity, acting on a glycoprotein" (GO:0140103).
Consistent with that, I note that GO:0033842 and EC:2.4.1.244 specifically mention 'glycoprotein' in the term name (though not in the definition).

This may reflect why we have the two separate GO terms.
Indeed, PMID:17498683 (the source of the 3 FlyBase annotations to GO:0033207) describes the 2 fly enzymes as working in glycosphingolipid synthesis (so not glycoprotein).

So....I return to my original proposal: GO:0033207 (the more generic term) should be the parent of GO:0033842 (a more specific term, in that it specifies a glycoprotein substrate).

And/or we could make a new specific term for the 2 fly enzymes (and maybe the worm enzyme??) to specify the glycolipid substrate.

Thoughts?

[sjm41]

Reviewing this (yet) again:

id: GO:0033842
name: N-acetyl-beta-glucosaminyl-glycoprotein 4-beta-N-acetylgalactosaminyltransferase activity
def: "Catalysis of the reaction: UDP-N-acetyl-D-galactosamine + N-acetyl-beta-D-glucosaminyl group = UDP + N-acetyl-beta-D-galactosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl group." [EC:2.4.1.244]
xref: EC:2.4.1.244
xref: RHEA:20493

The current EC/RHEA def for this is:
an N-acetyl-beta-D-glucosaminyl derivative + UDP-N-acetyl-alpha-D-galactosamine = an N-acetyl-beta-D-galactosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl derivative + UDP + H+.

That is, it is not specific for a glycoprotein, as the current GO/EC name suggests.

So, there are now 3 tasks to be done to close this issue:

• Update GO:0033842 name and def to use 'derivative'
• Merge GO:0033207 into GO:0033842
• GO:0033207 currently has one other child (GO:0033208), shown below. The term has no annotations and no db xrefs, so can be obsoleted. (The def does refer to two PMIDs, which appear to be about human B4GALNT2 (Q8NHY0), which is linked (but not annotated) to EC:2.4.1.165 in UniProt, so it's possible that GO:0033207 is the same as GO:0047233/EC:2.4.1.165, but I haven't checked this in depth. Regardless, given there's no annotations, it seems easiest and safest just to obsolete GO:0033207

[sjm41]

@pgaudet I've updated the name and def. Could you take care of the merge and obsoletion? thanks.

[pgaudet]

Neither EC:2.4.1.165 nor RHEA:13569 have any genes associate, so let's obsolete.

Made a request to RHEA to obsolete RHEA:13569.