Review annotations to receptor activity

[pgaudet]

The definition of 'receptor activity' "Combining with an extracellular or intracellular messenger to initiate a change in cell activity. " is almost the same as 'signaling receptor activity' "Receiving a signal and transmitting the signal in the cell to initiate a change in cell activity. A signal is a physical entity or change in state that is used to transfer information in order to trigger a response."

These two terms will be merged, see https://github.com/geneontology/go-ontology/issues/15234

Please review your annotations to make sure that the annotation was indeed for 'signaling receptor activity' , NOT a 'cargo receptor activity'.

https://docs.google.com/spreadsheets/d/18zaDTpRQzAgy6rvNqHDMS4ZxlcmoUGKZA18CuciwExM/edit#gid=0

Affected groups

AgBase @jinhuiz ARUK-UCL BHF-UCL CGD @marekskrzypek FlyBase GO_Noctua HGNC @RLovering MGI RGD SGD SGN ?? TIGR ?? UniProt WB ZFIN InterPro

[slaulederkind]

RGD has no manual annotations for 'signaling receptor activity'.

[srengel]

addressed these 4 annotations for the 3 genes in Sc. for 2 of the genes i changed it to 38024. for the other gene, i removed it.

[hattrill]

I have a quite a few to go through (~30 genes) - some easy, some not so easy (as they are adhesion receptors that can signal). Should have reviewed them by the start of next week, I hope!

[RLovering]

Hi I have checked the annotations for UCL

1. Slc40a1 (mouse and ISS'd to human) annotation removed.
2. I have updated Q9UNE0 to GO:0004888 transmembrane signaling receptor activity
3. all edits completed, no other edits required

Ruth

[RLovering]

Hi All

I am interested to hear that Helen has adhesion molecules annotated to receptor activity. I have a feeling that many adhesion molecules signal and I was wondering how this was going to be captured. I would like people to consider reinstating the term: GO:0004895 cell adhesion receptor activity which was removed when people decided adhesion wasn't a function ;(

Another option might be to create the term: GO:0098631 cell adhesion mediator activity GO:0004888 transmembrane signaling receptor activity

is_a Child new term: cell adhesion mediator receptor activity

If this seems reasonable let me know and I will submit a request

Thanks

Ruth

[hattrill]

It doesn't seem too unreasonable! The majority of annotations are ISS/NAS/TAS, so probably ancient and will go straight to bin. Integrins, planar cell polarity are a classic example of signaling/adhesion cross-overs. I'll let you know when I've poked them with my large stick

(Only ~6 genes have exp annotations.)

[pgaudet]

I had forgotten to add the link to the spreadsheet, here it is: https://docs.google.com/spreadsheets/d/18zaDTpRQzAgy6rvNqHDMS4ZxlcmoUGKZA18CuciwExM/edit#gid=0

If you already fixed the annotations, would you please anyway go in and mark them in the spreadsheet ?

Thanks, Pascale

[bmeldal]

Scanned through complexes (260!): all look like classic signalling receptors. Including all the integrins!

[vanaukenk]

I updated our one WB annotation to GO:0004888 transmembrane signaling receptor activity.

[pgaudet]

Thanks to all !

@bmeldal you are OK with integrin being a signalling receptor, or do you prefer the adhesion signaling term ?

[bmeldal]

It's fine, they are annotated with "transmembrane signaling receptor activity" and "cell-matrix adhesion". That should do.

[RLovering]

But they should also be annotated to GO:0098631 cell adhesion mediator activity to ensure consistant annotation

also see NTR cell adhesion receptor activity #15237

[bmeldal]

But they should also be annotated to GO:0098631 cell adhesion mediator activity to ensure consistent annotation

Do you mean the integrins, Ruth? Yes, I can add it. (They were done before my time...)

also see NTR cell adhesion receptor activity #15237

If we end up with a new/reinstated term cell adhesion signaling receptor activity I'll wait with doing edits.

[slaulederkind]

All RGD annotations for "receptor activity" have been checked, changed, or deleted.

[RLovering]

We also need some annotation guidelines here because the distinction between signalling receptors and cargo receptors is very difficult and it is not clear to me if we will expect curators to apply both terms for some receptors. Because: 1a. in order to initiate endocytosis and ‘cargo’ transport, cargo receptors often need to signal to the cell to initiate the process of endocytosis. I am happy for us to have the distinction that 'cargo receptors' just signal for endocytosis and I think it should be possible to create this definition. 1b. I also agree that the guidelines should state that these receptors should be annotated to the process of endocytosis because the ‘cargo’ is only endocytosed if it is bound to the receptor. 2a. However, this is also complicated by the fact that signalling receptors are often endocytosed and their ligands removed as part of receptor recycling. So in a way the signalling receptor is a ‘cargo receptor’ for the ligand. For example the insulin receptor regulates the amount of insulin in the body by removing it from circulation (PMID: 1476159 insulin receptor endocytosis). 2b. Or do we just say that 'signaling receptors' are not annotated to 'endocytosis' because they are endocytosed as part of the process of moderating the activity of the receptor? In which case they would not be annotated to 'cargo receptor' for 'insulin' in example above.

I therefore think a decision needs to be made about how to capture this information.

Ruth

[pgaudet]

Thanks for describing the potential confusion here @RLovering I'd like to discuss with @vanaukenk @ukemi @thomaspd to provide guidelines - and we should later discuss this on an annotation call.

[ukemi]

I had the same question as @RLovering . In many cases, the receptors that bind to molecules that activate signaling pathways also endocytose to recycle the receptors and sometimes to regulate the pathway.

[asangrador]

Hi, InterPro annotations are reviewed and done. We had 44 annotations to 'receptor activity', and most of them are fine (they correspond to 'signaling receptor activity') ; I only had to change or delete 7. I found that nomenclature is confusing in some cases, for example the' Catecholate siderophore receptor Fiu' (P75780) is involved in siderophore transport, so apparently is not a receptor despite its name.

[hattrill]

Reviewed all ours. Only 5 genes experimental. One changed to cargo receptor activity - would appear to be endocytosis-degradation rather than classical signaling, so ping us when decision made on where these will sit. Checked all the NAS/TAS/ISS, removed the majority.

[sabrinatoro]

ZFIN annotations were reviewed.

[pgarmiri]

UniProt annotations have been reviewed. Only one is pending but the PIR curator has been contacted and hopefully that will be updated soon. Changes have been report on the excel sheet.

[ukemi]

MGI annotation checks completed.