NTNU P12755 SKI is this a dbTF or a coTF

RLovering commented 4 years ago

Hi Marcio

Ruth Lovering	07-MAY-2020	I don't think there is sufficient evidence to suggest this protein binds DNA. InterPro does not associated the GO term DNA binding with the InterPro record IPR009061 nor with IPR010919 IPR010919 record discusses how SKI (related to this gene) disrupts Tx:Ski is able to disrupt the formation of a functional complex between the Co- and R-SMADs, leading to the repression of TGF-beta, Activin and BMP responses, resulting in the repression of TGF-signalling

Marcio Luis Acencio | 11-MAY-2020 | Lambert et al 2018 classifies this protein in DbTF and provide the following comment: Binds specifically to GTCTAGAC via EMSA in one study (PMID: 9452486). But, needs to form complexes with other proteins, such as NFI, to bind to DNA in another (PMID: 9380514). Related to SKIL, which also has evidence for DNA binding (PMID: 9824161)

Ruth response to above 20/5/2020 Thanks for the papers, ideally these papers should be annotated. However, the annotation based on InterPro are incorrect because these record do not provide evidence for DNA binding. Please remove these ISM annotations.

I need more time to check these papers, but thank you so much for providing them.

Thanks

Ruth

pgaudet commented 4 years ago

@mlacencio

RLovering commented 4 years ago

The EMSA in PMID: 9452486 uses nuclear extract. It seems to me that there is no evidence that this protein binds DNA on its own. However, following discussions with Arttu and Colin that SKOR1-2 do bind DNA based on HT-SELEX data the decision to annotate these proteins as dbTFs has been made. I do not think we should remove the coTF annotations as it looks like SKIL binds to TAF110 and therefore the requirement for another

RLovering commented 4 years ago

Sorry I forgot this issue was also about the use of InterPro IDs that do NOT support the annotation they are associated with. I have asked Pascale to create a dbTF annotations based on expt evidence in 2 papers.

Your dbTF annotations based on interpro domains still need to be removed as they are not inline with GOC guidelines.

Therefore please delete the following 2 annotations

Also note that neither SKI nor SKIL are listed as DNA binding in the Yin HT-SELEX data set, and SKI has been shown not to bind DNA unless it is in a complex with other dbTFs

Thanks Ruth

mlacencio commented 4 years ago

Hi @RLovering,

Annotations removed! I will take a look again at SKI and SKIL to try to find out why they are classified as DbTF by Lambert et al 2018.

Thanks!

Marcio

RLovering commented 4 years ago

Hi Marcio

Thanks for helping so much with this. FYI Following Colin's advice we have decided to curate these as dbTFs by PAINT based on the fact that the SKOR DNA binding domain is present in SKI and SKIL.

If you can find evidence to support SKI and SKIL as dbTFs that would be great, but if there is no literature to support this, at least a decision has been made at the moment for these. Please do add your findings to this ticket so that we can close it which ever way the decision goes

Best

Ruth

mlacencio commented 4 years ago

Hi @RLovering !

Although SKI and SKIL have been considered DbTF and are/will be annotated via PAINT, me, Astrid and Martin think that both proteins could be well annotated as DbTF supported by IDA taking into consideration, respectively, PMID:9452486 and PMID: 9824161. Why?

According to the new guidelines under preparation, sequence-specific DNA binding activity can now be demonstrated by ChIP as long as other requirements are met, namely, presence of DBD and experimentally validated transcriptional activity. We think that EMSA with nuclear extract and ChIP are equivalent in their ability to show DNA binding activity. In both types of experiment we can't guarantee that the protein of interest is directly binding DNA and then we need extra evidence such as the presence of DBD and demonstration of transcription activity. Therefore, as SKI and SKIL have DBDs and in both PMID:9452486 and PMID: 9824161 papers the DNA binding activity is shown via EMSA supershift with nuclear extract and transcription activity is shown via promoter reporter gene assay, then we think these papers could be used for IDA annotation of SKI and SKIL.

Best,

Marcio

colinlog commented 4 years ago

very good, we all agree that these are dbTFs indeed.

On Mon, Jun 22, 2020 at 5:23 PM Marcio Luis Acencio < notifications@github.com> wrote:

Hi @RLovering https://github.com/RLovering !

Although SKI and SKIL have been considered DbTF and are/will be annotated via PAINT, me, Astrid and Martin think that both proteins could be well annotated as DbTF supported by IDA taking into consideration, respectively, PMID:9452486 and PMID: 9824161. Why?

According to the new guidelines under preparation, sequence-specific DNA binding activity can now be demonstrated by ChIP as long as other requirements are met, namely, presence of DBD and experimentally validated transcriptional activity. We think that EMSA with nuclear extract and ChIP are equivalent in their ability to show DNA binding activity. In both types of experiment we can't guarantee that the protein of interest is directly binding DNA and then we need extra evidence such as the presence of DBD and demonstration of transcription activity. Therefore, as SKI and SKIL have DBDs and in both PMID:9452486 and PMID: 9824161 papers the DNA binding activity is shown via EMSA supershift with nuclear extract and transcription activity is shown via promoter reporter gene assay, then we think these papers could be used for IDA annotation of SKI and SKIL.

Best,

Marcio

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pgaudet commented 4 years ago

Thanks everyone !

geneontology / go-annotation

NTNU P12755 SKI is this a dbTF or a coTF #2985