NTR: microtubule stabilizing activity (was: NTR:microtubule severing inhibitor activity)

[magrane]

Please provide as much information as you can:

• Suggested term label: ~negative regulation of microtubule severing (& parent 'regulation of microtubule severing')~

• Will create the MF: microtubule severing inhibitor activity

• Definition (free text) Any process that stops, prevents, or reduces the frequency, rate or extent of the breaking down of a microtubule into smaller segments

• Reference, in format PMID:####### PMID:34970964 (shows that SSNA1 protects microtubules from severing by spastin)

• Gene product name and ID to be annotated to this term human SSNA1 (O43805)

• Parent term(s) GO:0051013 (microtubule severing)

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

[ValWood]

Sorry to complicate this but:

We have a number tickets to migrate of actin -related processes that are really "activities" out of the BP ontology. We would eventually want to do the same for microtubule processes that are single-step, like "microtubule severing".

This new term might be better are a Molecular function "microtubule serving inhibitor"

Here is a related (open) ticket for actin severing activity, and actin severing inhibitor https://github.com/geneontology/go-ontology/issues/18437

[pgaudet]

~I created this:~

~+[Term] +id: GO:0140775 +name: microtubule severing inhibitor activity +namespace: molecular_function +def: "Binds to and stops, prevents, or reduces the activity of a microtubule severing protein." [PMID:34970964] +is_a: GO:0140678 ! molecular function inhibitor activity +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23014 xsd:anyURI +created_by: pg +creation_date: 2022-03-22T10:23:35Z~ +

But I am not sure this is right - I think this is a microtubule stabilizer activity. We dont have 'stabilizer' as molecular function, but I think that would be useful? I remember we mentioned that before, but I cannot find where...

Thanks, Pascale

[ValWood]

stabilizer might be better. We have talked about "stabilizer' a lot, particularly in the context of RNA binding proteins that stabilize mRNAs. I'm not sure if it ever made it into a ticket.

[pgaudet]

This is from an email exchange with Paul, David and Kimberly:

• Protein stabilizer: binds to and protects a protein from degradation or unfolding, resulting in a higher level of active protein.
• (m)RNA stabilizer: binds to and protects an mRNA from degradation, resulting in a higher level of transcribed product. (this would address this: https://github.com/geneontology/go-ontology/issues/20132)

However we need to see how that fits with the BP:

• GO:0031647 regulation of protein stability
• • GO:0036506 maintenance of unfolded protein
• • GO:0031648 protein destabilization
• • GO:0050821 protein stabilization as well as the RNA terms:
• GO:0043487 regulation of RNA stability
• • GO:0043488 regulation of mRNA stability
• • GO:0044357 regulation of rRNA stability
• • GO:0036415 regulation of tRNA stability
• • GO:0050779 RNA destabilization
• • GO:0043489 RNA stabilization

These are potentially phenotypes , as @ValWood mentioned in https://github.com/geneontology/go-ontology/issues/20132#issuecomment-755229210

"stability" has multiple meanings. There is the very direct "binding to a protein or mRNA to stabilize it" (MF), but stability is also used for stability of protein or mRNA is over its lifetime" which is not really determined by a single process, but is a balance between translation, or mRNA/protein catabolism. So, is stabilization itself really a process ?

[pgaudet]

So, I will change the new term ~GO:0140775~ microtubule severing inhibitor activity, to 'microtubule stabilizing activity', and put that as a child of the new term GO:0140777 protein-containing complex stabilizing activity see #23062

@magrane Does that work for you ?

Thanks, Pascale

EDITED: Note that the term creation was not complete, so I'll start over with the 'microtubule stabilizing activity'

[pgaudet]

+[Term] +id: GO:0140778 +name: microtubule stabilizing activity +namespace: molecular_function +def: "A protein-containing complex stabilizing activity that prevents dissociation of microtubules," [PMID:34970964] +is_a: GO:0140777 ! protein-containing complex stabilizing activity +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/23014 xsd:anyURI +created_by: pg +creation_date: 2022-03-23T13:20:26Z

[pgaudet]

Maybe we'll need to improve the term labels and definitions later. Right now all examples are on protein complexes (microtubules and actin filaments). Also the definition doesn't mention protection from degradation.

This is a bit restrictive because we don't want to overlap with chaperones, sequestering and other activities.

[pgaudet]

@ccasalsc