A few receptor-related terms

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I was annotating a gene product that interacts with the glucocorticoid receptor and synergistically activates transcription. GO has the glucocorticoid receptor activity - GO:0004883 - but not receptor binding. PMID: 11279115 New GO glucocorticoid receptor binding Definition: Interacting selectively with the glucocorticoid receptor a steroid hormone activated nuclear r receptor which upon ligand binding can associate with transcription factors and regulate transcription.
PMID: 12151000 I would not use ligand as a synonym. The ligand per se is the hormone, but the receptor, which also is a regulator, can interact with other proteins.

I would also propose the parent term New GO: steroid hormone receptor binding Definition : interacting with one or several of the steroid receptors I have a gene product that does so. PMID: 11739747

Maybe even a higher node parent for hormone receptor binding. A little bit of an issue here: The nuclear hormone receptor activity is the synonym for for ligand-dependent nuclear receptor activity - GO:0004879. There is a GO term for ligand-dependent nuclear receptor interactor activity - GO:0016922 with definition : Ligand dependent interaction with nuclear receptor proteins. I would not consider this the same as the respective receptor binding activities my gene products exhibit since their interaction with the receptors, in itself, is ligand independent. It is actually the receptor that upon ligand binding, is capable of interacting with other proteins and I dont think it carries the ligand dependence over to the proteins it interacts with. In fact out of the nine annotations to the term (AmiGO) some are for gene products that may be part of the receptor complex.. In one case - PMID: 7776974 proteins fell into two categories: those that required the presence, and those that required the absence of the hormone ligand. Maybe we could have ligand-dependent and ligand-independent nuclear receptor binding and then binding to the individual receptors. Interactor sounds a bit unusual I found a Java class but not a def in OneLook.

I was annotating a gene product that is a toll-lie receptor PMID: 12616494 GO has Toll binding - GO:0005121 definition: Interacting selectively with the Toll protein, a transmembrane receptor and synonym - Toll receptor binding New GO - Toll receptor activity (sensu Drosophila). Definition a transmembrane receptor essential for ontogenesis and antimicrobial resistance in insects. PMID: 11167369 New GO - Toll-like receptor activity, definition -
interacting with bacterial components to induce an inflammatory response, may play important roles in the adaptive immune response. Some of the toll-like receptors may require the presence of an adaptor protein. PMID: 11805536 PMID: 15241424 Note: the Toll-like came about to distinguish the mammalian paralogs thirteen of them as of today
from the Drosophila counterpart

I have a gene product that interacts with metabotropic glutamate receptors PMID: 9069287 All GO terms for the various glutamate receptors are for activity only, Possible new terms GO new: metabotropic glutamate receptor activity. Definition any of the glutamate receptors that couple to G proteins and affect intracellular messenger systems. Based on signal transduction mechanisms, sequence homology and response to agonists they can further be subdivided into three groups. PMID: 12879970 GO new metabotropic glutamate receptor binding. Definition - interacting selectively with a metabotropic glutamate receptor. PMID: 9069287

Group II and III metabotropic glutamate receptors activities are in GO: GO:0001641 and GO:0001642, respectively under adenylate cyclase inhibiting metabotropic glutamate receptor activity - GO:0001640. There is also a group I which is not negatively coupled to adenylyl cyclase but to activation of phospholipase C GO new - group I metabotropic receptor activity (child of GOnew metabotropic receptor activity. Definition A G-protein coupled receptor for glutamate that is coupled to phospholipase C activation. Group I metabotropic glutamate receptors can modulate other neurotransmitter receptors, participate in a range of CNS functions and have been implicated in a number of diseases. PMID: 10416961

Reported by: vpetri

Original Ticket: "geneontology/ontology-requests/2004":https://sourceforge.net/p/geneontology/ontology-requests/2004

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Hi Victoria,

I agree that ligand-dependent nuclear receptor binding would be a better name for GO:0016922. I also think the current parentage for GO:0016922 is incorrect and should be changed from:

receptor activity ; GO:0004872 --%ligand-dependent nuclear receptor interactor activity ; GO:0016922

to:

receptor binding ; GO:0005102 --%ligand-dependent nuclear receptor interactor activity ; GO:0016922

I'd prefer not to have a sensu Drosophila Toll receptor term. I'm currently changing the sensu Drosophila terms to broaden them to other flies/insects. Also most information in the suggested definition is best captured by annotating to process terms since Drosophila Toll has roles in a number of processes including D/V pattern formation, hemopoiesis and immunity.

I'm not sure about the usefulness of a 'Toll receptor' term. In most other X receptor terms, x is the ligand. So a Toll receptor term describes a gene product more than a function. Drosophila Toll is currently annotated with the function terms transmembrane receptor activity and cytokine binding. Again, annotating to the relevant process terms (eg adaptive immunity) would capture the info in the definition for the suggested Toll-like receptor term.

Finally- in case you haven't seen it, there's another SF item open on the glutamate receptors: SF:1004045 (ionotropic/metabotropic glutamate receptors) which ties in with your glutamate receptor terms:

thanks, Becky

Original comment by: beckyfoulger

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Hi Becky,

I guess you meant changing from receptor activity ; GO:0004872 --%ligand-dependent nuclear receptor interactor activity ; GO:0016922

to

receptor binding ; GO:0005102 --%ligand-dependent nuclear receptor binding activity ; GO:0016922 (rather than interactor).

How about the ligand-independent binding PMID: 7776974? Should this be a sibling of ligand-dependent binding?

I'm afraid that this ligand dependence/independence issue makes things murky. However could we have

steroid hormone receptor binding activity and glucocorticoid receptor binding activity?

I agree with you on the Toll issue.

I looked up the SourceForge entry on ionotrpic/glutamate receptors.
The class I metabotropic is still missing. Group I is not negatively coupled to adenylyl cyclase but to activation of phospholipase C. To have the term would also be consistent with the fact that there is a process term - metabotropic glutamate receptor, phospholipase C activating pathway - GO:0007206 - which is mediated by memebrs of the group I metabotropic receptors.

Why are there two terms for GABA B receptors? GABA-B receptor activity - GO:0004965 and metabotropic glutamate, GABA-B-like receptor activity synonym -class C G-protein coupled receptor - GO:0008067

GABA B is the metabotropic GABA receptor (in contrast to GABA A which is ionotropic).

The metabotropic GABA B receptors, together with the eight metabotropic blutamate receptors (further divided intro three classews), the calcium sensing receptor and some putative taste and odor receptors, constitue the C family of G-prorein coupled receptors. PMID: 11805536 PMID: 15241424 PMID: 12782243

GABA receptors bind GABA but fall in three subtypes GABA A and GABA C are are both ligand-fated Cl channels BABA B iis metabotropic and couples to Ca and K channels via G proteins. PMID: 15269338 PMID: 12891648

I think we should keep the GABA B term GO:0004965 and take out the glutamate term GO:0008067 It is also wrong as a child of glutamate receptor activity.

The definitions also need fixing GABA A and GABA B are not neurotrnasmitters but subtypes of GABA receptors.

I realize this is a long and complicated issue which if consistently fixed would probably also affect the branching of G-protein coupled receptors

I would not mind working on the issue - I brought it with me to the Cambridge camp but then I didn't think it belonged there.

Thanks,

Victoria

Original comment by: vpetri

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Hi Victoria,

Sticking with the hierarchy in the receptor section....in the receptor binding section I'd suggest:

receptor binding ; GO:0005102 --%nuclear hormone receptor binding ; GO:NEW ----%steroid hormone receptor binding ; GO:NEW ------%androgen receptor binding ; GO:0050681 ------%glucocorticoid receptor binding ; GO:NEW ------%estrogen receptor binding ; GO:0030331 ----%thyroid hormone receptor binding ; GO:0046966 ----%vitamin D receptor binding ; GO:0042809 ----%retinoic acid receptor binding ; GO:0042974 ------%retinoid X receptor binding ; GO:0046965 [new relationship]

I noticed the following term was obsoleted: name: ligand-dependent thyroid hormone receptor interactor activity ; GO:0016923 def: "OBSOLETE. Ligand dependent interaction with the thyroid hormone receptor." [PMID:7776974] So is GO:0016922 still a valid term? Are X-dependent binding terms allowed?

For the glutamate receptors:

I think the existing GO:0001639 term describes the group I metabotropic glutamate receptor term you are after: PLC activating metabotropic glutamate receptor activity ; GO:0001639. PLC should be spelled out in a new synonym for GO:0001639 for searching purposes.

In my other SF item, I suggested changing GO:0008067 just to 'metabotropic glutamate receptor'. This would avoid having GABA-B-like in the text string. I don't think it should be removed, because then there would be no generic term to annotate (and group) metabotropic glutamate receptors. That would make it:

metabotropic glutamate receptor activity ; GO:0008067 --%GABA-B receptor activity ; GO:0004965 % GABA receptor activity

from what you say, should the following relationship be added then: ?

ionotropic glutamate receptor activity ; GO:0004970 --%GABA-A receptor activity ; GO:0004890

I agree the definitions of the GABA-A and GABA-B receptors need tweaking- perhaps something along the lines of:

Combining with the neurotransmitter GABA (gamma aminobutyric acid) to initiate a change in cell activity.GABA-A receptors function as chloride channels.

Combining with the neurotransmitter GABA (gamma aminobutyric acid) to initiate a change in cell activity. GABA-B receptors are G-protein coupled receptors.

(or something better worded)

David Hill did alot of work on G-protein coupled receptors, with an external expert, a little while back so he (and others) would know more about these receptors.

what do you think? thanks, Becky

Original comment by: beckyfoulger

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Hi Becky,

I love the receptor binding /nuclear receptor hierarchy you describe below. If the ligand-depndent thyroid term was obsoleted then GO:0016923 should be too and yes, I'd avoid x-dependent binding terms.

For the glutamate I agree, GO:0001639 is the group I acrivity. However, for consistency, since you have the group II and II I would have the group I as the name of the term and the PLC activating description in the synonym or the definition. These is how they are usually referred to, or known. Eight metabotropic glutamatre receptors, each having several genes Group I mGlu1 mGlu5 Group II mGlu2 mHlu3 Group III mGlu4 mGlu6 mGlu7 mGlu8

Why the glutamate receptors are not under neurotransmitter receptor activity, like GABA and others?

GABA GABA is NOT a glutamate receptor. I would keep it as it is under neurotransmitter receptor activity and remove it from glutamate. Under GABA receptor activity, I'd have GABA A and GABA B with definitions along the lines you propose that could spell out the channel or metabotropic nature.

And, the eight metabotropic glutamate receptors (in three classes), the two GABA B receptors (metabotropic GABA), the Ca sensing receptor and several putative pheromone and taste receptors together form the family 3, or family C of GPCR, based on structural features. The other two are represented by the rhodospin and related receptors family and the secretin family, respectively. However, other families have been ideitifed (frizzled, pheromones).

Some classifications include both vertebrates and invertebrates (A-F system) , some are for human nad probaly all are changing as novel receptors are discovered, I think the GPCR issues could be brought more up-to-date.

For now I would just go over the GABA,glutanate issues, if possible renaming the PLC activating activity as the grop I having the glutamate receptor activities also as children of neurotramitter receptors {else we may anger the major excitatory neurotranmitter with unforseeable consequences) revise the GABA A abd GABA B definitions as you suggest and do not list GABA under glutamate

What do you think?

The nuclear hromone receptors below look good

Thanks, Victoria

Original comment by: vpetri

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Hi Victoria,

Sorry for the delay in replying- I'd like a general glutamate receptor binding term for annotation of the Drosophila Grip gene, so how about the following:

receptor binding ; GO:0005102 --%glutamate receptor binding ; GO:NEW ----%metabotropic glutamate receptor binding ; GO:NEW ----%ionotropic glutamate receptor binding ; GO:NEW

--%G-protein-coupled receptor binding ; GO:0001664 ----%metabotropic glutamate receptor binding ; GO:NEW

Interacting selectively with a glutamate receptor

Interacting selectively with a metabotropic glutamate receptor. Metabotropic glutamate receptors are G-protein coupled receptors that bind glutamate and exert an effect through the regulation of enzyme activity. ISBN:0198506732 PMID: 9069287

Interacting selectively with an ionotropic glutamate receptor. Ionotropic glutamate receptors bind glutamate and exert an effect through the regulation of ion channels. ISBN:0198506732

If glutamate always functions as a neurotransmitter, then yep- glutamate receptor activity ; GO:0008066 should have neurotransmitter receptor activity ; GO:0030594 as a parent.

I'll defer to people who know more about G-protein coupled receptors for your GABA receptor parentage and glutamate receptor nomenclature suggestions :) I'm happy to implement the new receptor binding terms though if they're ok with you.

Becky

Original comment by: beckyfoulger

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Hi Becky,

Thank you for your reply. The changes for the glutamate receptors are fine with me and I'll wait for you to implement them. For now, GABA can wait. Are you also going to implement the changes you desctribed earlier for the nuclear hormone recetpros? They are further down this page. Sorry I had several issues in the same request. Thank you for your help,

Victoria

Original comment by: vpetri

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I've added in the following new function terms in the hierarchy described below: GO:0035254 BF glutamate receptor binding GO:0035255 BF ionotropic glutamate receptor binding GO:0035256 BF metabotropic glutatmate receptor binding GO:0035257 BF nuclear hormone receptor binding GO:0035258 BF steroid hormone receptor binding GO:0035259 BF glucocorticoid receptor binding

Modified the definitions of GABA-A receptor activity ; GO:0004890 and GABA-B receptor activity ; GO:0004965 to:

Combining with the neurotransmitter GABA (gamma aminobutyric acid) to initiate a change in cell activity. GABA-A receptors function as chloride channels. and Combining with the neurotransmitter GABA (gamma aminobutyric acid) to initiate a change in cell activity. GABA-B receptors are G-protein coupled receptors.

Added the following synonyms to PLC activating metabotropic glutamate receptor activity ; GO:0001639. phospholipase C activating metabotropic glutamate receptor activity group I metabotropic glutamate receptor activity

I will send an email to the list proposing the obsoletion of the mis-positioned term ligand-dependent nuclear receptor interactor activity ; GO:0016922.

I haven't done anything to the nomenclature of the glutamate receptors. I haven't done anything to the parentage of the GABA receptors.

I will leave these to people who know more about GPCRs and the work that has been done on them already.

thanks, Becky

Original comment by: beckyfoulger

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Hi Becky

Thank you very much.

Victoria

Original comment by: vpetri

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Based on the Chicago GO meeting, and plans to use synonyms where possible and reduce obsoletions, I plan to merge ligand-dependent nuclear receptor interactor activity ; GO:0016922 into nuclear hormone receptor binding ; GO:0035257. And I'll remove the receptor activity parentage.

Becky

Original comment by: beckyfoulger

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Hi,

Does anything else need to be done for this, or can we close it?

m

Original comment by: mah11

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Hi Midori,

You can close the item.

Thanks,

Victoria

Original comment by: vpetri

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• status: open --> closed-fixed

Original comment by: mah11

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OK; thanks for checking!

m

Original comment by: mah11

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• milestone: --> TermGenie
• assigned_to: nobody --> beckyfoulger

Original comment by: mah11