NTR: pH-gated channel activity terms about go-ontology

[raymond91125]

I think X-dependent ion channel and X-gated ion channel are synonymous. PMID: 30930064 states: "Protonation of Asp171 leads to an open-state structure." This is consistent with the notion that pH changes is gating the channel. It is however true that these articles don't necessary use the word "gate". We could add "pH-dependent" and "pH-sensitive" as equivalent synonyms.

[raymond91125]

+[Term]
+id: GO:0160128
+name: pH-gated channel activity
+namespace: molecular_function
+def: "Enables the transmembrane transfer of a solute by a channel that opens in response to a change in proton concentration (pH)." [PMID:17167423, PMID:29513651]
+synonym: "acid-sensing ion channel activity" RELATED []
+synonym: "proton-gated ion channel activity" RELATED []
+is_a: GO:0022836 ! gated channel activity
+property_value: term_tracker_item "#26444" xsd:anyURI
+created_by: rynl
+creation_date: 2023-11-29T00:03:01Z

[pgaudet]

@lbreuza
Sorry, I just noticed this, but since all children of the grouping class 'pH-gated channel activity' transport monoatomic ions, could we change the label and definition of the GO:0160128 pH-gated channel activity to reflect that?

[lbreuza]

#26520

Also, please add a comment on 'GO:0160128 pH-gated channel activity' to explain that while the term suggest this activity may be proton-gated, the mechanism of pH-gating for transporters is by protonation of specific residues in the protein, and not by H+ binding.
Thanks, Pascale

I'm not sure if there is a difference between proton binding and protonation in this context, though. PMID:34136464.

I would suggest "pH-gated channel activity and proton-gated channel activity are often used interchangeably as they refer to the same mechanism of activation of a channel through protonation of some residues upon decrease in pH"

[pgaudet]

@hattrill can you please provide references for these activities?

[hattrill]

Sorry, @pgaudet: PMID:34767445 for both.

plus PMID:30930064 for pH-gated calcium channel activity term

[raymond91125]

+[Term]
+id: GO:0160125
+name: pH-gated sodium channel activity
+namespace: molecular_function
+def: "A gated channel activity that enables the transmembrane transfer of a sodium ion by a channel that opens in response to a change in pH." [PMID:34767445]
+is_a: GO:0022836 ! gated channel activity
+relationship: has_primary_input CHEBI:29101 ! sodium(1+)
+property_value: term_tracker_item "" xsd:anyURI
+created_by: rynl
+creation_date: 2023-11-21T00:50:09Z
+
+[Term]
+id: GO:0160126
+name: pH-gated calcium channel activity
+namespace: molecular_function
+def: "A gated channel activity that enables the transmembrane transfer of a calcium ion by a channel that opens in response to a change in pH." [PMID:30930064, PMID:34767445]
+is_a: GO:0022836 ! gated channel activity
+relationship: has_primary_input CHEBI:29108 ! calcium(2+)
+property_value: term_tracker_item "#26444" xsd:anyURI
+created_by: rynl
+creation_date: 2023-11-21T00:56:00Z

[pgaudet]

@hattrill

Looking at the paper again, it seems this is not 'gating', but regulation. The paper talk about

pH-dependent calcium and sodium channel

so I propose we change the label to 'pH-activated x channel activity'. What do you think ?

[hattrill]

Would be consistent with Ca2+ act term, so fine with that.

A lot of papers use gating and activation/regulation interchangably. But, if we use activated for ions and gating for molecules, that is consistent.

[raymond91125]

It's pH-dependent, not necessarily pH-activated. (C, black squares)

[pgaudet]

Thanks for the feedback Raymond.

That works for me. To me the confounding issue is that we have both 'gated' and 'activated' channels, with no clear reason why there is an inconsistency. For example 'activated' includes
GO:0015275 stretch-activated, monoatomic cation-selective, calcium channel activity >> OK ?

The following should be changed to 'gated'?
GO:0005222 intracellular cAMP-activated cation channel activity
'calcium-activated cation channel activity'
'calcium-activated potassium channel activity'
'chloride-activated potassium channel activity'

I think for calcium the gating is not via direct calcium binding, but the terms are under 'gated channel activity'.

If we could be more consistent that'd be great.

Thanks, Pascale

[lbreuza]

Hi,
could we also add a parent term pH-gated channel activity for channels that a re not substrate specific like ZACN (PubMed=26872532).
Ligand-gated cation channel permeable to the sodium and potassium monoatomic cations and gated by zinc (Zn2+), copper (Cu2+) and pH.
"We demonstrate that Cu2+ and H+ also are agonists of ZAC, which consequently should be considered
a Zn2+, Cu2+- and pH-sensing receptor." I guess one can replace sensing by gated in that sentence of the paper.
Best, Lionel

[pgaudet]

Hi @raymond91125

Are you planning to create the grouping class, pH-gated channel activity, as requested by @lbreuza ?

Thanks, Pascale

[lbreuza]

Hi @raymond91125,
I also found proton-gated ion channels PMID: 38002313. Could it be something different?
Thanks, Lionel

[raymond91125]

A family tree of ion channels https://www.guidetopharmacology.org/GRAC/ReceptorFamiliesForward?type=IC

[pgaudet]

Hi @raymond91125

Would you please change the asserted classes to a logical definition for the 3 new terms?

[raymond91125]

#26520

Also, please add a comment on 'GO:0160128 pH-gated channel activity' to explain that while the term suggest this activity may be proton-gated, the mechanism of pH-gating for transporters is by protonation of specific residues in the protein, and not by H+ binding.

Thanks, Pascale

I'm not sure if there is a difference between proton binding and protonation in this context, though. PMID:34136464.