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Source ontology files for the Gene Ontology
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relax def for GO:1990746 HCN4 channel complex #11897

Closed gocentral closed 6 years ago

gocentral commented 9 years ago

Hi,

Anna created the above term but there is actually a family of HCN channel complexes. In order to avoid the explosion of the ontology and in agreement with our recent meeting, I think we should relax the name & def and allow all HCN Cx to be annotated to this term, making the isoforms narrow synonyms.

ID GO:1990746 -Name HCN4 channel complex +Name HCN channel complex Ontology Cellular Component -Definition HCN4 tetramer is a hyperpolarization-activated ion channel with selectivity for potassium over sodium ions. HCN4 is the dominant form of HCN expressed in the heart, together with HCN2. HCN4 expression is particularly high in the sinoatrial node, where impulses initiate and propagate throughout the heart. There is pharmacologic and genetic evidence that the HNC4 channel complex plays a role in cardiac pacemaking and automaticity, by contributing to the native pacemaker current of the heart (If). Mutations in the C-terminus containing the C-linker and CNBD domain, which affect the expression or function of the HCN4 channel are known to cause arrhythmias or bradycardia. +Definition A hyperpolarization-activated ion channel with apparent selectivity for potassium over sodium ion voltage-gated channel activity. Expressed in the heart and brain where it controls pacemaker activity. Activated dually by membrane hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD). PMID:20829353

Thanks, Birgit

Reported by: bmeldal

Original Ticket: geneontology/ontology-requests/11735

gocentral commented 9 years ago

Forgot:

narrow synonyms: HCN1 channel complex K/Na hyperpolarization-activated cyclic nucleotide-gated channel 1 complex Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 complex

HCN2 channel complex K/Na hyperpolarization-activated cyclic nucleotide-gated channel 2 complex Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 complex

HCN4 channel complex K/Na hyperpolarization-activated cyclic nucleotide-gated channel 4 complex Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 complex

Exact synonyms: K/Na hyperpolarization-activated cyclic nucleotide-gated channel complex Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel complex

They are also all tetrameric. Do you still want that info in the def?

Birgit

Original comment by: bmeldal

gocentral commented 9 years ago

Original comment by: dosumis

gocentral commented 9 years ago

I just saw that Anna also created GO:1990759 HCN2 channel complex. This should probably also be obsoleted.

Birgit

Original comment by: bmeldal

bmeldal commented 9 years ago

Ok, further additions:

HCN3 is not activated by cAMP and HCN1 only weakly activated by cAMP (it is constitually activated by basal concentrations of cAMP) so I think we need to relax the def even further:

+Definition A hyperpolarization-activated ion channel with apparent selectivity for potassium over sodium ion. All members are activated by membrane hyperpolarization and some members (HCN1, HCN2 & HCN4 isoforms) by binding of cAMP to their cyclic nucleotide binding domain (CNBD). Capable of voltage-gated potassium and sodium channel activity. Expressed in the heart and brain where it controls pacemaker activity. Homotetrameric but can have additional, regulatory subunits.

We also need a further relationship: is_a GO:0001518 voltage-gated sodium channel complex

And NARROW synonyms for the HCN3 isoforms: HCN3 channel complex K/Na hyperpolarization-activated channel 3 complex Potassium/sodium hyperpolarization-activated channel 3 complex

I also have suggestions to tidy up the related activity terms. Shall I make a new ticket for them? It would eventually require changing the capable_of relationships (which need fixing here anyway as they only point to GO:0005249 voltage-gated potassium channel activity at the moment, via it's parent term, not directly here).

dosumis commented 9 years ago

is_a GO:0001518 voltage-gated sodium channel complex

Should do this via inference using capable_of

bmeldal commented 9 years ago

is_a GO:0001518 voltage-gated sodium channel complex

Should do this via inference using capable_of

Ok. Do you want the capable_of relationships as the ontology stands right now or do you want to make the changes to the activity terms first, then change the relationships here on the complex? And should I add the activity change request here or make a separate ticket?

dosumis commented 9 years ago

This needs mention of the composition:

+Definition A hyperpolarization-activated ion channel with apparent selectivity for potassium over sodium ion voltage-gated channel activity. Expressed in the heart and brain where it controls pacemaker activity. Activated dually by membrane hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD).

How about:

A cation ion channel with a preference for K+ ions, which is activated by membrane hyperploarization, and consists of a tetramer of HCN family members. Some members of this family are also activated when cAMP binds to their cyclic nucleotide binding domain (CNBD). [Channel complexes of this family have an important role in the control of pacemaker activity in the heart.] capable_of: voltage-gated potassium channel activity

[Ispum Lorem] = optional gloss

bmeldal commented 9 years ago

Suggestion:

A cation ion channel with a preference for K+ over Na+ ions, which is activated by membrane hyperploarization, and consists of a tetramer of HCN family members. Some members of this family (HCN1, HCN2 and HCN4) are also activated when cAMP binds to their cyclic nucleotide binding domain (CNBD). Channel complexes of this family play an important role in the control of pacemaker activity in the heart.

Also add: capable_of: voltage-gated sodium channel activity

dosumis commented 9 years ago

Added HCN channel complext "A cation ion channel that consists of a tetramer of HCN family members, has a preference for K+ over Na+ ions and is activated by membrane hyperpolarization. Some members of this family (HCN1, HCN2 and HCN4) are also activated when cAMP binds to their cyclic nucleotide binding domain (CNBD). Channel complexes of this family play an important role in the control of pacemaker activity in the heart."

Do you have a ref for the Na+ channel activity?

Also wondering if we could better reflect what cAMP activation means. Here's a quote from PMID: 20829353 "cNMP binding shifts the voltage-dependent channel activation curve toward more positive potentials, increasing the macroscopic current amplitude and making the channel activate faster and deactivate slower."

On Mon, Sep 28, 2015 at 10:57 AM, Birgit notifications@github.com wrote:

Suggestion:

A cation ion channel with a preference for K+ over Na+ ions, which is activated by membrane hyperploarization, and consists of a tetramer of HCN family members. Some members of this family (HCN1, HCN2 and HCN4) are also activated when cAMP binds to their cyclic nucleotide binding domain (CNBD). Channel complexes of this family play an important role in the control of pacemaker activity in the heart.

Also add: capable_of: voltage-gated sodium channel activity

— Reply to this email directly or view it on GitHub https://github.com/geneontology/go-ontology/issues/11897#issuecomment-143697715 .

bmeldal commented 9 years ago

Do you have a ref for the Na+ channel activity?

Funny you are asking that! It's like searching for a needle in a haystack and I'm doing that right now! All papers mention K+/Na+ channel activity with preference for K+ but the papers cited 'only' describe patch clamp expts without any indication that they assessed the type of ion beyond what's in the buffers. I have never worked on this in the lab so I might just be missing something. The 3 papers that are already annotated in GO are PMID:16407510, 10228147 & 22748890. I also have 16043489 which claims a 3:1 ratio for HCN3.

Also wondering if we could better reflect what cAMP activation means. [...]

Do you want a longer def or a gloss comment? As I mentioned, the whole detail about how ICs are working is only starting to become clear to me. I never worked on them myself but all theses channels were submitted by ChEMBL for curation. I wonder if they have anyone who knows more about it???

bmeldal commented 9 years ago

Hi David,

here my suggestions for the changes to the activity terms:

HCN channels are inward rectifying K+/Na+ channels, 3 of 4 are activated by cAMP (HCN1, HCN2 & HCN4, not HCN3)

Therefore, GO:1990746 HCN channel complex can have:

capable_of GO:0005242 inward rectifier potassium channel activity GO:0005248 voltage-gated sodium channel activity (or new child, see below) GO:0005217 intracellular ligand-gated ion channel activity (do we need a ‘cation’ child term?)

As HCN3 is NOT activated by cAMP, we cannot use more specific terms for the ontology links, however, I can use such terms for the complex annotations in the CP, so I’m proposing an extension to the current terms as follows:

1) GO:0005222 intracellular cAMP activated cation channel activity Def: “Enables the transmembrane transfer of a cation by a channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts.”

create new children:

GO:NEW1 intracellular cAMP activated potassium channel activity is_a GO:0005222 intracellular cAMP activated cation channel activity Def: “Enables the transmembrane transfer of a potassium ion by a channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts.”

and

GO:NEW2 intracellular cAMP activated sodium ion channel activity is_a GO:0005222 intracellular cAMP activated cation channel activity Def: “Enables the transmembrane transfer of a sodium ion by a channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts.”

2) GO:0005242 inward rectifier potassium channel activity Def: “Enables the transmembrane transfer of a potassium ion by an inwardly-rectifying voltage-gated channel. An inwardly rectifying current-voltage relation is one where at any given driving force the inward flow of K+ ions exceeds the outward flow for the opposite driving force. The inward-rectification is due to a voltage-dependent block of the channel pore by a specific ligand or ligands, and as a result the macroscopic conductance depends on the difference between membrane voltage and the K+ equilibrium potential rather than on membrane voltage itself.”

Note: I see where your comment from yesterday came from! This is indeed slightly confusing. As far as I know, inward rectifying channels are activated by membrane voltage (in the case of the HCN channels reaching a certain hyperpolarisation level) rather than relative ion concentrations. I feel we might need an expert to help with the definitive def!

create child:

GO:NEW3 GO:0015272 cAMP activated inward rectifier potassium channel activity (as there is already the equivalent “GO:0015272 ATP-activated...” child) is_a GO:0005242 inward rectifier potassium channel activity is_a GO:NEW1 intracellular cAMP activated potassium channel activity Def: “Def: “Enables the transmembrane transfer of a potassium ion by an inwardly-rectifying voltage-gated channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts. An inwardly rectifying current-voltage relation is one where at any given driving force the inward flow of K+ ions exceeds the outward flow for the opposite driving force.”

3) GO:0005248 voltage-gated sodium channel activity Def: “Enables the transmembrane transfer of a sodium ion by a voltage-gated channel. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.”

create child:

GO:NEW4 inward rectifier sodium channel activity is_a GO:0005248 voltage-gated sodium channel activity is_a GO:0015276 ligand-gated ion channel activity Def: “Enables the transmembrane transfer of a sodium ion by an inwardly-rectifying voltage-gated channel. An inwardly rectifying current-voltage relation is one where at any given driving force the inward flow of Na+ ions exceeds the outward flow for the opposite driving force. The inward-rectification is due to a voltage-dependent block of the channel pore by a specific ligand or ligands, and as a result the macroscopic conductance depends on the difference between membrane voltage and the Na+ equilibrium potential rather than on membrane voltage itself.” (NB1: see notes on the K+ channel above (GO:0005242) regarding clarifying the def.) (NB2: this would be the better capable_of term as well then)

create child:

GO:NEW5 GO:0015272 cAMP activated inward rectifier sodium channel activity is_a GO:NEW4 inward rectifier sodium channel activity is_a GO:NEW2 intracellular cAMP activated sodium channel activity Def: “Def: “Enables the transmembrane transfer of a sodium ion by an inwardly-rectifying voltage-gated channel that opens when intracellular cAMP has been bound by the channel complex or one of its constituent parts. An inwardly rectifying current-voltage relation is one where at any given driving force the inward flow of Na+ ions exceeds the outward flow for the opposite driving force.”

4) GO:0005248 voltage-gated sodium channel activity (see pt 3) also has the child:

GO:0086006 voltage-gated sodium channel activity involved in cardiac muscle cell action potential with child GO:0086063 voltage-gated sodium channel activity involved in SA node cell action potential

which is, in principle, also applicable to the HCN channels. However, the HCN channels are also found in other cells (neurons). Can we use these as capable_of relations in the ontology or just annotation in the CP? In any case, we could create the K+ equivalents, as HCN channels are preferentially K+ channels (ratios reported btw 3:1 and 4:1 against Na+).

New terms would be:

GO:NEW6 voltage-gated potassium channel activity involved in cardiac muscle cell action potential is_a GO:0005249 voltage-gated potassium channel activity Def: “Enables the transmembrane transfer of a potassium ion by a voltage-gated channel through the plasma membrane of a cardiac muscle cell contributing to the depolarization phase of an action potential. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.”

and

GO:NEW7 voltage-gated potassium channel activity involved in SA node cell action potential is_a GO:NEW6 voltage-gated potassium channel activity involved in cardiac muscle cell action potential Def: “Enables the transmembrane transfer of a potassium ion by a voltage-gated channel through the plasma membrane of an SA node cardiac muscle cell contributing to the depolarization phase of an action potential. A voltage-gated channel is a channel whose open state is dependent on the voltage across the membrane in which it is embedded.”

I think the existing cardiac terms were created for/by Ruth’s group.

dosumis commented 7 years ago

I've been working on overhauling gated ion channels as part of MF refactoring. Will work on this further later in Jan + Feb. May spin this aspect off into new ticket(s). Couple of thoughts

bmeldal commented 7 years ago

@dosumis do you need anything from me right now?

pgaudet commented 6 years ago

Hi @bmeldal

Is this right ?

Thanks, Pascale

bmeldal commented 6 years ago

Thanks, @pgaudet that looks good except for the spelling of "hyperploarization" ;-)

@dosumis what do you want to do about the activity terms?

pgaudet commented 6 years ago

@bmeldal can this one be closed ? I fixed the typo.

bmeldal commented 6 years ago

@pgaudet please close.

@dosumis please open a new ticket if you ant to make further changes during the MF refracturing.