search

geneontology / go-ontology

Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
Creative Commons Attribution 4.0 International
223 stars 40 forks source link

actin filament severing activity? #18437

Open ValWood opened 4 years ago

ValWood commented 4 years ago

Is there any reason why

"actin severing" is a BP and not an MF (has related synonym actin filament severing activity?)

ValWood commented 4 years ago

https://en.wikipedia.org/wiki/Cofilin

for eample has "severing" activity

ValWood commented 4 years ago

The child "actin filament debranching" is also a severing activity (but this time specifically at the branch point). There are only 5 EXP annotations and all are to cofilin a 'debranching enzyme'

I did not check the annotations to the parent "actin filament severing"

pgaudet commented 4 years ago

The MF was obsoleted: 

GO:0003789

Name obsolete actin filament severing activity Ontology molecular_function Comment This term was made obsolete because it describes a biological process.

ValWood commented 4 years ago

but 'severing' is a single gene product activity?

pgaudet commented 4 years ago

Is 'severing' just hydrolysis of an actin monomer from the actin fibre ? Or is it the net sum of adding and removing ?

ValWood commented 4 years ago

MY undrestanding is that severing is "internal" to the actin filament. Severing increases depolymerization by increasing the number of 'ends'

pgaudet commented 4 years ago

Discussion with @ValWood :

Thanks, Pascale

pgaudet commented 4 years ago

@ValWood Look at dispute in for UniProtKB:P35579 From me:

Hi, We plan to obsolete this term (see https://github.com/geneontology/go-ontology/issues/18437) The paper states "binding of NMMIIA to gelsolin minimally reduced the severing activity of gelsolin" - do you think that has biological relevance ? if so, we can create a term 'negative regulator of actin-severing activity'. Thanks, Pascale | Pascale Gaudet, 17-JAN-2020 10:58

Penelope:

Hi Pascale, Thank you for your comment. The minimal effect was observed on the planar surfaces. On the beaded surfaces the effect was large and regulated by calcium influx. On Fig 7, there is a schematic model of this (see below the description). So, perhaps the new term you suggested with an AE relation happens_during 'response to calcium ion' would work? Thanks, Penelope FIGURE 7: Schematic model of calcium regulation of gelsolin interaction with NMMIIA. Cell adhesion to topologically complex collagen substrate induces [Ca2+]i flux, which promotes interaction of NMMIIA rods with gelsolin domains G1G3 and G4G6. This interaction enhances actin remodeling by gelsolin at collagen adhesion sites to enable collagen phagocytosis. Low [Ca2+]i inhibits binding of NMMIIA with gelsolin domains G4G6, which results in reduced actin remodeling and inhibition of collagen phagocytosis.

ValWood commented 4 years ago

In this case this sounds more like a MF than a BP?

"actin severing inhibitor"?

pgaudet commented 4 years ago

@pgarmiri would ""actin severing inhibitor activity" work for you ?

pgarmiri commented 4 years ago

Yes, that sounds good to me. Thanks

ValWood commented 2 years ago

Hi can this be actioned?

actin filament severing activity Needed for PMID: 23727096 Actin filament severing by cofilin dismantles actin patches and produces mother filaments for new patches

Also the "actin severing ~inhibitor~ activator activity" - see https://github.com/geneontology/go-ontology/issues/18437#issuecomment-1072091373 required for PMID:25451933 Aip1 promotes actin filament severing by cofilin and regulates constriction of the cytokinetic contractile ring.

I spotted these annotations are not yet made while approving a new paper from the same lab: PMID:34613787

ValWood commented 2 years ago

~I think GO:0051014 actin filament severing should also be obsoleted? Do you want me to punt the obsoletions to another ticket?~

deustp01 commented 2 years ago

In the brave new world of Noctua and GO-CAM, why is a new term needed rather than an annotation of the appropriate protease MF enabled by the gene product that does the severing, acting on actin?

ValWood commented 2 years ago

Hi Peter,

cofililin and gelsolin aren't proteases. The mechanism is some sort of twisting of the polymer and the conformational change forces separation of 2 actin monomers. v

ValWood commented 2 years ago

Hi @pgaudet are we ready to proceed with this?

pgaudet commented 2 years ago

Hi @ValWood

Isn't Aip1 an 'actin severing activator activity' ? It seems to increase the efficiency of cofilin?

pgaudet commented 2 years ago
ValWood commented 2 years ago

yes sorry Aip1 is an activator

pgaudet commented 2 years ago

+[Term] +id: GO:0000513 +name: actin severing activator activity +namespace: molecular_function +def: "Binds to and increases the activity of a actin severing protein." [PMID:25451933] +is_a: GO:0140677 ! molecular function activator activity +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/18437 xsd:anyURI +created_by: pg +creation_date: 2022-03-18T08:10:20Z

pgaudet commented 2 years ago

Any thoughts about where to put 'actin filament severing activity'? Right now it's directly under molecular_function, but it seems this could be a more general function -

perhaps something like 'protein-complex destabilizing activity' (and we could have protein/protein complex stabilizing activity'? which I think would be more appropriate for #23014)

Thanks, Pascale

pgaudet commented 2 years ago

Need to find a parent class for this term

ValWood commented 2 years ago

I'm not sure about a grouping class. MAybe wait until we have other terms to group...may become more obvious.

pgaudet commented 2 years ago

How about some type of chaperone ?

ValWood commented 2 years ago

I thought I commented on this one- it doesn't seem like a chaperone. I wouldn't look for it here...

ValWood commented 2 years ago

Note that here PomBAse required the 'actin severing activity'. Tthe activator was for UiniProt

pgaudet commented 2 years ago

@ValWood I suppose I should also create 'actin debranching activity' to replace the BP GO:0071846 actin filament debranching (child of GO:0051014 actin filament severing)

pgaudet commented 2 years ago

Dear all,

The proposal has been made to obsolete:

The reason for obsoletion is that these represent molecular functions. There are 46 EXP annotations to these terms: https://docs.google.com/spreadsheets/d/1zkpYipUvcRMZL6yuLE_CpeNjrwwSxUzV3DsotDNtDrc/edit#gid=0

Group | Number of EXP -- | -- dictyBase | 2 FlyBase | 1 GeneDB | 1 MGI |  2 PomBase |8 RGD | 1 SGD | 6 TAIR | 3 UniProt | 17 WB | 5

There are also InterPro and UniRule mappings:

TO COMPLETE annotations should be replaced by:

pgaudet commented 2 years ago

+[Term] +id: GO:0140775 +name: actin filament debranching activity +namespace: molecular_function +def: "Binding to an actin filament and promoting the dissociation of an actin filament branch." [PMID:20362448] +synonym: "actin debranching activity" EXACT [] +is_a: GO:0003674 ! molecular_function +relationship: has_part GO:0051015 ! actin filament binding +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/18437 xsd:anyURI +created_by: pg +creation_date: 2022-03-23T07:37:53Z

pgaudet commented 2 years ago

I created the terms needd to replace the BPs. I'll ask for reannotation after the Noctua maintenance is done tomorrow.

ValWood commented 1 year ago

Hmm, we might need to keep "actin severing" as a process too.

So we have MFs actin filament severing activity actin severing inhibitor activity but also there are gene products like Aip1, I spotted this when I was migrating my actin severing annotations.

Aip1 Aip1 increases up to 12-fold the rate that high concentrations of yeast or human cofilin sever actin filaments, most likely by competing with cofilin for binding to the side of actin filaments, reducing the occupancy of the filaments by cofilin to a range favorable for severing. PMID: 25451933 (I think it was this one?)

So Aip1 isn't a "actin severing regulator" in the GO sense, because it doesn't exert its activity by binding directly to the cofilin. I don't know how we would annotate this to capture its role in severing?

pgaudet commented 1 year ago

Isn't that still actin cytoskeleton organization?

ValWood commented 1 year ago

I suppose, but for something we know quite precisely the mechanism of action the annotation would be

MF lateral actin binding part of actin cytoskeleton organization

This isn't really going to place it precisely in a model of the actin cytoskeleton?