geneontology / go-annotation

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Necdin NDN MGI:97290 #3541

Closed RLovering closed 1 year ago

RLovering commented 3 years ago

Hi Harold

sorry this request was not submitted properly because it was slipped into another ticket: https://github.com/geneontology/go-annotation/issues/3167

The initial request was for the dbTF annotations associated with Cys1 to be removed, which you kindly did. But Colin also pointed out in this ticket that Necdin NDN MGI:97290 is not a dbTF either. However, based on the same Cys1 paper https://pubmed.ncbi.nlm.nih.gov/24349431/ MGI has the annotations:

Ndn | enables | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | ECO:0000314(IDA) | PMID:24349431 | Ndn | enables | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | ECO:0000314(IDA) | PMID:24349431 | has_input(MGI:MGI:97250)

Please could you change one of these to GO:0003713 transcription coactivator activity and delete the other annotation as Colin explained in the Cys1 ticket: 'Finally, NDN (NECDIN) is a member of the Panther protein family PTHR11736 most of which are known ubiquitin ligase associated proteins (eg MAGEA2 -- MAGEL2, ) that influence transcription but do not have demonstrated sequence-specific DNA binding domains'.

Note that the authors state that cystin-necdin act as a regulatory complex

To be honest you might want to review all the annotations associated with this paper. I haven't read the paper fully but you have Cys1 annotated as a corepressor that positively regulates transcription. I think this comes from section 'Cystin antagonizes necdin to modulate Myc P1 promoter activity' and figure 6. I think I would have annotated Cys1 as a coactivator and a corepressor and to both positive and negative regulation of transcription. Whereas NDN appears to be just a coactivator positively regulating transcription.

Also, rather than just protein binding you could also apply these terms:

GO:0001225 RNA polymerase II transcription coactivator binding GO:0001226 RNA polymerase II transcription corepressor binding

And as NDN is not a dbTF then the Cys1 annotation negative regulation of DNA-binding transcription factor activity needs to change. Although we don't seem to have the coregulator activity equivalent term. I will raise a ticket to see if the equivalent terms can be created.

Many thanks

Ruth

RLovering commented 3 years ago

HI Karen

I have discussed this situation with Pascale and Colin and they have pointed out that as Cys1 and NDN are both within this coregulator complex we should capture both proteins as coregulators (probably corepressors).

Also Pascale confirmed that BP terms that describe regulation of an MF are being removed from the ontology and so the equivalent terms for coregulators will not be added. I hope this is helpful

best

Ruth

RLovering commented 3 years ago

Hi @krchristie

Our list of DNA-binding transcription factors is about to be published. The reviewers have asked us to comment on whether a specific filter in AmiGO or QucikGO will download this list. Currently there are a few MGI annotations that mean that applying the GO:0003700 filter will lead to several non-dbTF proteins being downloaded. One of these is Ndn.

It would be great if this annotation could be removed so that our users can download a list of dbTFs without also downloading in appropriate coTFs. If you are not happy with this suggestion please confirm this so that we can explain in the article that there are still some annotations that remain outstanding and are yet to be removed

Thanks

Ruth

RLovering commented 1 year ago

Hi Ruth,

I also removed the DNA binding annotation since it seemed indirect. It looks like Ndn interacts with the transcription factor, not the DNA.

-David