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#10426 General Ras GTPase terms
Afraid this is a rather general point that covers a lot of terms. I think that the terms related to Ras GTPases might benefit from some renaming and new terms to help define the Ras subfamily. The Ras superfamily major subfamilies are Ras, Rab, Rho, Ran, Arf. Currently most Ras process/function terms have the Ras parent term which applies to the superfamily and the children referring to the specific subfamilies (e.g. Rho, Arf). The child terms do not include the Ras subfamily itself (although there are some Ras sub-sub families like Ral & Rap).
e.g. Parent: GO:0005099 Ras GTPase activator activity
Children: GO:0005097 Rab GTPase activator activity
GO:0005098 Ran GTPase activator activity
GO:0005100 Rho GTPase activator activity
GO:0017123 Ral GTPase activator activity
GO:0046582 Rap GTPase activator activity
The same is true of other Ras superfamily relationships, e.g.
GO:0032856 activation of Ras GTPase activity
GO:0017016 Ras GTPase binding
GO:0046579 positive regulation of Ras protein signal transduction
GO:0034261 negative regulation of Ras GTPase activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
I'm not sure what the best approach is: requesting new Ras sub-family-specific GOs would result in a very similar name to the parent term.
This may also be an issue for other families with sub-families that share the same name e.g. Rho family with Rho and Rac subfamilies.
Making terms for subfamilies of the RAS protein superfamily, and of their accessory GAP and GEF proteins, sounds right. Maybe a way to think about where / how to draw boundaries is to look for RAS families (subfamilies?) that are involved in distinct and non-overlapping processes: ones that mediate vesicle movement, for example, as distinct from ones that transduce signals originating at the cell surface. Once could also distinguish RAN from the rest because the rest toggle between an active GTP-bound state and an inactive GDP bound one while RAN GTPases are active in both states, albeit with different activities. Sounds like a topic for a small expert workshop.
Hello,
I know I brought that up before - but just to be sure we're aware that the functions of the small GTPases (both general and specific) have been obsoleted. For example:
GO:0003925 small monomeric GTPase activity
GO:0003928 RAB small monomeric GTPase activity
etc.
However we do have 'Rab activator activity', Rab regulation, Rab exchange factor activity, ect.
To me this is inconsistent, because if there is a Rab GTPase activator activity, I expect to also see a Rab activity - but I may be misunderstanding our practices.
Thanks,
Pascale
We could just merge all the specific child terms into the parent, GTPase activator activity. Existing annotations would still be valid, if less specific. Same goes for +/- regulation of xxx GTPase activity, these could be merged into +/- regulation of GTPase activity.
IIRC, our last conversation was that if there were clearly discernible differences in how the Ras vs. Rab vs. Rho, etc GTPase functions were accomplished, then individual terms were warranted but if the mechanism of action was the same, it did not make sense to have different MF terms based only on differences in the name of the encoding gene product.
My original comment now looks wrong - focusing specifically on what these proteins do as enzymes, they all bind GTP and, when activated, catalyze its hydrolysis, so one molecular_function term could cover all of them. The distinctions among them come about other ways, particularly in their binding interactions with GAP and GEF proteins.
Here is a good recent review Regulation of small GTPases by GEFs, GAPs, and GDIs. PMID:23303910; DOI: 10.1152/physrev.00003.2012
From my point of view ....I think that it sounds fine for one MF term for all. There are differences in the detailed molecular mechanism between the different classes of GAPs/GEFs, but ultimately all GEFs displace GDP, stabilize the NT-free form and facilitate GTP loading; all GAPs stabilize the transition state and facilitate GTP hydroylsis.
There can be more than one class of GAP/GEF for any given Ras subfamily, and some may act on more than subfamily. I think this is best captured by protein binding terms - although Ras GTPase binding is the parent term for the other Ras-subfamilies with no Ras subfamily:
(Ran GTPase binding
Rho GTPase binding
Rab GTPase binding
Ral GTPase binding)
If I can throw in another point (mainly because I am feeling sentimental about "small monomeric GTPase activity") - I'd like to be able to distinguish between GTPases that use GTP hydrolysis to drive an event (coupled) and GTPases that use GTP hydrolysis/binding to switch between states. May be this is seen as the same thing? Perhaps this just muddies the water? I certainly can't think of a good MF for a molecular switch, which is not much help.
There are a few term that do a similar job for more specific cases (e.g. GTP-dependent helicase activity; membrane scission GTPase motor activity, GTP-dependent protein binding).
Helen
"I'd like to be able to distinguish between GTPases that use GTP hydrolysis to drive an event (coupled) and GTPases that use GTP hydrolysis/binding to switch between states. May be this is seen as the same thing? Perhaps this just muddies the water?"
I think it muddies the water but others may disagree.
Does this make sense?
ARF GTPase activator activity
Ras GTPase activator activity
Sar GTPase activator activity
Rab GTPase activator activity
Ral GTPase activator activity
Ran GTPase activator activity
Rap GTPase activator activity
Rho GTPase activator activity
Rac GTPase activator activity
merge 'small GTPase regulator activity' into 'GTPase regulator activity', move children up to be direct children of 'GTPase regulator activity' before the merge
merge the following terms into 'regulation of GTPase activity'
regulation of Ras GTPase activity
regulation of ARF GTPase activity
regulation of Rab GTPase activity
regulation of Ral GTPase activity
regulation of Ran GTPase activity
regulation of Rap GTPase activity
regulation of Rho GTPase activity
merge relevant positive and negative regulation of XXX GTPase activity terms into the appropriate positive and negative regulation of GTPase activity terms
create 'activation of GTPase activity' and merge the following terms into that one
activation of ARF GTPase activity
activation of Cdc42 GTPase activity
activation of Rab GTPase activity
activation of Rac GTPase activity
activation of Ral GTPase activity
activation of Ran GTPase activity
activation of Rap GTPase activity
activation of Ras GTPase activity
activation of Rho GTPase activity
Please comment by next Wednesday, 2/11. Thanks.
Hi Tanya,
That all seems sensible to me. Thanks!
Could I request modifications to the small GTPase binding terms?
Current:
GO:0017016 Ras GTPase binding has the children:
GO:0008536 Ran GTPase binding
GO:0017048 Rho GTPase binding
GO:0017137 Rab GTPase binding
GO:0017160 Ral GTPase binding
I'd quite like to be able to add back a bit of granularity by being able to specify binding to each subfamily. These terms below would be useful to me:
Ras GTPase subfamily binding
Arf GTPase binding
Rag (or RRAG) GTPase binding
and
Sar GTPase binding as a child of Arf GTPase binding
(Note: Arf GTPases can be divided into Arf, Arl, Sar and Arp subfamilies)
Rho GTPase subfamily binding as a child of Rho GTPase binding (and a change of definition to indicate that this is the Rho family, not subfamily).
Rap GTPase binding as a child of Ras GTPase subfamily binding
and Ral GTPase binding moved under Ras GTPase subfamily binding
Thanks, Helen.
I finished all the merges of activation/pos regulation/neg regulation/regulation/activator activity/small GTPase into GTPase regulator activity. It took about an hour and half!!
Putting off the binding edits till another day.
Helen, could you do me a huge favor and type in the structure that you'd like to see.
Right now, it looks something like this:
GTPase binding
--[i] small GTPase binding
----[i] ADP-ribosylation factor binding
----[i] Ras GTPase binding
------[i] Rab GTPase binding
------[i] Ral GTPase binding
------[i] Ran GTPase binding
------[i] Rho GTPase binding
--------[i] GTP-Rho GTPase binding
--------[i] Rac GTPase binding
Please copy this as a template and add in the terms you want that are new and add a GO:new to them. You can also rearrange as you want to see the terms in their final structure.
This would help me a great deal.
Thanks,
Tanya
Hi Tanya,
Sorry, took me much more than a week to get back to this!
I am afraid it all gets a bit messy as there are lots of Family > Subfamily relationships. Not sure if this is would be really clear from a user's perspective. Well, it's a start and as these subfamilies can be distinguished by GEF/GAP classes and other efffectors, it seems reasonable to distinguish binding terms.
GTPase binding
--[i] small GTPase binding
----[i] Rag GTPase binding
----[i] Ras Superfamily GTPase binding
------[i] Ras Family GTPase binding
--------[i] Ras Subfamily GTPase binding
--------[i] Ral GTPase binding
--------[i] Rap GTPase binding
------[i] Rab GTPase binding
------[i] Ran GTPase binding
------[i] Rho Family GTPase binding
--------[i] Rho Subfamily GTPase binding
--------[i] Rac GTPase binding
------[i] Arf Family GTPase binding
--------[i] Sar GTPase binding
--------[i] Arl GTPase binding
--------[i] Arf Subfamily GTPase binding
(I have left a few potential ones out from the Ras Family members Rit, Rheb and Rad, Rho Cdc42 and the Arf sub-family Arp as I am not so sure about their interactions - I am going to review the small GTPases soon, so could add them to the existing structure if needed)
Thanks,
Helen
On 12 Feb 2015, at 01:20, Tanya Berardini wrote:
Related
Ontology requests: #10426
Hi Tanya,
Sorry to add to your load, but... As you mentioned edits on parentage of general Ras GTPase terms, could you please take a look at discussion in the SF ticket below:
https://sourceforge.net/p/geneontology/ontology-requests/11536/
Many thanks,
Paola
Hi Helen,
We're not ignoring your protein family binding-related request, just having lots of internal discussions. This may come up on the All hands call on April 1st (no joke) so we will hopefully have resolution on the protein family binding topic after that.
Thanks for your patience,
Tanya
That's fine. It is quite a tricky one and I don't think what I have suggested is a really great option - too much scope for confusion.
Thanks,
Helen
On 13 Mar 2015, at 21:20, Tanya Berardini wrote:
Related
Ontology requests: #10426