GTPase, heterotrimeric, monomeric

[gocentral]

Proposal of 2 new terms and maybe some obsolescences as well, relating to heterotrimeric and small monomeric G proteins.

SGD had genes annotated to each of three terms that recently went obsolete:

heterotrimeric G-protein GTPase, alpha-subunit ; GO:0000263 heterotrimeric G-protein GTPase, beta-subunit ; GO:0000264 heterotrimeric G-protein GTPase, gamma-subunit ; GO:0000265

No objections with the obsoletions, completely agree there. However, the suggested replacement term in the comment field is:

'heterotrimeric G-protein GTPase ; GO:0003927'

1a. In trying to re-annotate the 3 bits of a cerevisiae heteromeric G-protein, I'd really like to have terms like ', catalyst' and ', regulator', like what we do for cyclin-dependent kinases, so I'd like to propose two new terms:

%heterotrimeric G-protein GTPase ; GO:0003927 %heterotrimeric G-protein GTPase, catalyst ; GO:new %heterotrimeric G-protein GTPase, regulator ; GO:new

1b. The definition (below) for 'heterotrimeric G-protein GTPase ; GO:0003927' seems pretty bad. It would seem that the definition for this should be revised to be specific to heterotrimeric G proteins, and to remove the lists of example proteins and processes. Can this definition be revised with the same GOid?

2. In looking at this, I noticed a sibling term 'small monomeric GTPase: GO:0003925 ;'. Both respect to the term name "small monomeric ...", and the current definition (below), I question whether this GTPase term should be in the Function ontology when the distinguishing feature between it and its parent term 'GTPase' is merely that it is small and monomeric. Wouldn't just 'GTPase' be sufficient to define the function?

3. All current children of 'small monomeric GTPase ; GO:0003925' are specific gene products. Good candidates for obsolescence? regardless of the status of the parent term. Anything distinctive about the function of a "small monomeric GTPase" that merits distinction from just plain GTPase?

---- 2 existing, but awful defs ----

term: small monomeric GTPase goid: GO:0003925

definition: Small monomeric enzymes with a molecular mass of 21 kDa that are distantly related to the alpha-subunit of heterotrimeric G-protein GTPase. They are involved in cell-growth regulation (RAS subfamily), membrane vesicle traffic and uncoating (RAB and ARF subfamilies), nuclear protein import (RAN subfamily) and organization of the cytoskeleton (Rho and Rac subfamilies).

term: heterotrimeric G-protein GTPase goid: GO:0003927

definition: GTP-hydrolyzing enzymes, where GTP and GDP alternate in binding. Includes stimulatory and inhibitory G-proteins such as Gs, Gi, Go and Golf, targeting adenylate cyclase and/or potassium ion and calcium ion channels; Gq stimulating phospholipase C; transducin activating cGMP phosphodiesterase; gustducin activating cAMP phosphodiesterase.

Reported by: krchristie

Original Ticket: "geneontology/ontology-requests/524":https://sourceforge.net/p/geneontology/ontology-requests/524

[gocentral]

Logged In: YES user_id=436423

I'm going to forward this to the mailing list, in case anyone who's been ignoring SourceForge cares about it.

We should think about this a bit before we implement catalyst and regulator terms for heterotrimeric GTPases. In the case of CDKs (as an example), the regulatory subunit regulates the kinase activity of the catalytic subunit. It looks a bit more complicated for heterotrimeric G proteins: the beta & gamma subunits anchor the complex at the membrane, and (from what I'm reading in Alberts, at least), it looks as though GDP/GTP exchange precedes beta-gamma dissociation. So calling beta or gamma 'regulatory' may not work as well as the 'regulatory' part of CDK. Opinions?

I do agree that the definitions are yucky; do you have replacements ready, or do you want help coming up with some?

Also agree that the cildren of small monomeric GTPase are gene products, and small monomeric GTPase itself isn't function-y. I wouldn't object to making them obsolete.

Midori

Original comment by: mah11

[gocentral]

Logged In: YES user_id=382010

There exists GO:0005834 (Component:heterotrimeric G- protein complex) and GO:0003924 (Function:GTPase) and GO:0008277 (Process:regulation of G-protein coupled receptor protein signaling pathway). These three terms taken together describe each alpha, beta, and gamma subunit.
There are a few children of GO:0008277 that can be used specify whether the regulation is positive or negative. I'd say if, for instance, a Galpha-s were assigned GO:0045745 (Process:positive regulation of G-protein coupled receptor protein signaling pathway) on the basis of it being a Galpha-s without further experimental evidence in the context of the particular GPCR-GProtein complex, I would suggest Evidence Code IC (Inferred by Curator).

In light of my comments above, I'd suggest obsoleting GO:0003927 (heterorimeric G-protein GTPase) as it is not needed.

--- Courtland Yockey --- AstraZeneca Pharmaceuticals

Original comment by: ceyockey

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• assigned_to: kchris --> nobody

Original comment by: krchristie

[gocentral]

Logged In: YES user_id=473796

This was dealt with in the GTPase obsoletion item, SF:923074.

Both 'heterotrimeric G protein GTPase activity' and 'small monomeric GTPase activity' have now been rehomed in obsolete. The 'catalyst' and 'regulator' terms have all been taken out of function so if there is still some call for GTPase regulatory subunit terms, perhaps someone can submit another SF item requesting 'regulation of GTPase activity'. Ta!

Original comment by: girlwithglasses

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• assigned_to: nobody --> girlwithglasses
• status: open --> closed-fixed

Original comment by: girlwithglasses