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PTN001668995 #5598

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sjm41 opened this issue Jan 7, 2025 · 9 comments
Closed

PTN001668995 #5598

sjm41 opened this issue Jan 7, 2025 · 9 comments

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@sjm41
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sjm41 commented Jan 7, 2025

  • PTHR ID & PTN node:
    PTN001668995

  • Sequences with problematic annotation (ID + gene/protein name):
    Human Q96EY9/ADAT3
    Fly Q7K157/FBgn0034360

  • Type of Issue: Erroneous source or erroneous propagation, or other issue
    Not sure

Human Q96EY9/ADAT3 has the comment in UP "Caution - Val-225 is present instead of the conserved Glu which is an active site in the cytidine and deoxycytidylate deaminase family of enzymes. It is suggested that this protein may act as a regulatory subunit"

So I don't think PTN001668995 should propagate "contributes_to tRNA-specific adenosine-34 deaminase activity", which appears to be based on a single annotation to pombe SPAP27G11.04c (tad3)

@sjm41
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sjm41 commented Jan 7, 2025

PMID: 17875641 is the source for the "contributes_to tRNA-specific adenosine-34 deaminase activity" annotation to pombe tad3.
That paper says "The absence of the essential glutamate residue in the putative Tad3p deaminase domain suggests that Tad3p is catalytically inactive and that Tad2p is the catalytic subunit of the enzyme."

@ValWood Should the Tad3p annotation be changed to "NOT tRNA-specific adenosine-34 deaminase activity"?

@ValWood
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ValWood commented Jan 8, 2025

yep, it is annotated with contributes_to because it affects the activity.
But I guess it acts as a regulator?

@ValWood
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ValWood commented Jan 8, 2025

so do we need
tRNA-adenosine deaminase regulator activity?

@sjm41
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sjm41 commented Jan 8, 2025

The UP entry for pombe tad3 (https://www.uniprot.org/uniprotkb/Q9P7N4/entry) has s similar caution statement as the human ortholog, specifically:
Caution: In contrast to other cytidine and deoxycytidylate deaminase, lacks the conserved Glu active site in position 213 which is replaced by a Val residue, suggesting that it acts as a regulatory subunit.

And the PMID: 17875641 abstract also says: "Further analyses revealed that in the tad3-1 mutant cells, the S257N mutation that occurred in the catalytically inactive Tad3 subunit affected its association with catalytically active Tad2 subunit, leading to an impairment in the A to I conversion at position 34 of tRNA."

So, I would suggest the current "contributes_to tRNA-specific adenosine-34 deaminase activity IDA" annotation be replaced with these two annotations:
NOT tRNA-specific adenosine-34 deaminase activity IKR
enzyme activator activity IDA (I'm not sure we need a more specific term here?)

(You already have a "tRNA-specific adenosine-34 deaminase complex IDA" annotation from the same paper, which is good!)

@ValWood
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ValWood commented Jan 8, 2025

fixed

@ValWood ValWood removed their assignment Jan 8, 2025
@sjm41
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sjm41 commented Jan 9, 2025

fixed

Thanks @ValWood ! I guess that means you added both the annotations I suggested? I'd like to use the NOT annotation in an ISS annotation to the fly ortholog - do you know how it takes for PomBase GO annotations to get into P2GO?

@ValWood
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ValWood commented Jan 9, 2025

Yep, I made the NOT annotation. IIRC for PomBase, the annotations are picked up by GOA from from GO. This means they won't appear until a GO update followed by a GOA update.

@marcfeuermann
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Happy New Year.
I've also modified this at the PAINT level.

@sjm41
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sjm41 commented Jan 9, 2025

Thanks Mark!

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