Representing sensor activities

[vanaukenk]

On the 2024-08-26 ontology call we discussed how we'd like to represent gene products that function as molecular sensors.

Here are some of the relevant points we touched on:

1. Gene products are not limited to sensing small molecules, they may sense larger things like a stalled ribosome
2. Gene products that sense a molecule often (always?) do so as part of their overall function to regulate the activity of another gene product
3. We would prefer not to co-annotate a gene product to a 'sensor activity' MF as well as, for example, an 'enzyme inhibitor activity' term. One suggestion was to create a term like 'small molecule-activated enzyme inhbitor activity'. However, some gene products described as sensors clearly have other, well-defined activities (see 6 below).
4. The level of granularity for both the small molecule and the enzymatic activity affected is still TBD.
5. We may want to create a child of 'molecular function regulator activity' that is 'molecular sensor activity' and then house the existing sensor activity terms under that. A possible definition for 'molecular sensor activity': Binding to a molecule or higher order structure at a given level of that molecule or structure and, as a consequence of that binding, regulating the activity of a downstream gene product. PMID: 11595184, PMID:33986552
6. Use cases: Enzymes like PHD2 that hydroxylate HIF and are described as oxygen sensors. GMPPA that binds GDP-mannose to inhibit activity of GMPPB in GDP-mannose biosynthesis. ZAKalpha, a MAPKKK, that recognizes stalled ribosomes. Others?

@pgaudet @rozaru @sjm41 @ValWood @thomaspd @deustp01

[raymond91125]

Perhaps the design pattern is something like: molecular sensor activity and ('has primary input' some molecule) and ('directly regulates' some molecular function)

[rozaru]

6. Use cases: Enzymes like PHD2 that hydroxylate HIF and are described as oxygen sensors. GMPPA that binds GDP-mannose to inhibit activity of GMPPB in GDP-mannose biosynthesis. ZAKalpha, a MAPKKK, that recognizes stalled ribosomes. Others?

Another case could be the calcium sensor calmodulin that activates enzymes, channels etc (see CALM1)

I am not sure I am following what would happen with the potential new term in terms of hierarchy and annotation. Would it look like this?

[pgaudet]

The action items I understood from Monday's call are

• [x] 1. rename 'small molecule sensor activity' to 'molecular sensor activity'
• [x] 2. move stalled ribosome sensor activity under 'molecular sensor activity'
• [x] 3. move membrane curvature sensor activity under 'molecular sensor activity'
• [x] 4. move 'molecular sensor activity' under 'molecular regulator activity' >> for this we need to check that the annotations are consistent with this proposed parentage.