Restructure GO:0022857 transmembrane transporter activity branch

[hattrill]

The current structure of the GO:0022857 transmembrane transporter activity branch is not working very well for classifying TMTs. This is leading to some confusion over primary, secondary, faciltated diffusion and passive transport. See discussion on https://github.com/geneontology/go-ontology/issues/27340

The main framework currently this:

transmembrane transporter activity
    |__active transmembrane transporter activity
        |__primary active transmembrane transporter activity
        |__secondary active transmembrane transporter activity
            |__antiporter activity
            |__symporter activity
            |__uniporter activity
    |__passive transmembrane transporter activity
        |__channel activity

We propose that this structure, which is more inline with the current TC system would be less confusing:

transmembrane transporter activity
    |__primary active transmembrane transporter activity
    |__transmembrane carrier activity
        |__antiporter activity
        |__symporter activity
        |__uniporter activity
    |__channel activity
    |_group translocator activity 

The restructure would involve:

transmembrane transporter activity
    |__active transmembrane transporter activity **OBSOLETE** as unhelpful grouping term
        |__primary active transmembrane transporter activity
        |__secondary active transmembrane transporter activity **RENAME** to 'transmembrane carrier activity'
            |__antiporter activity
            |__symporter activity
            |__uniporter activity
    |__passive transmembrane transporter activity **OBSOLETE** as a single parent 'branch'
        |__channel activity
    |_group translocator activity **NEW**

[hattrill]

TASKS

• [x] Review direct children of GO:0022804 active transmembrane transporter activity
• [ ] obsolete GO:0022804 active transmembrane transporter activity
• [x] NTR: group translocator activity
• [ ] Review children of GO:001529 secondary active transmembrane transporter activity
• [ ] Rename and redefine GO:001529 secondary active transmembrane transporter activity
• [ ] obsolete GO:0022803 passive transmembrane transporter activity

[hattrill]

GO:0022804 active transmembrane transporter activity

• [ ] obsolete as confusing/inaccurate

---

-is_a GO:0046715 active borate transmembrane transporter activity

• [x] made tickets to obsolete and new terms for channels & reannotation

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-is_a GO:0022853 active monoatomic ion transmembrane transporter activity -All child terms are either GO:0015503 glutathione-regulated potassium exporter activity and GO:0015341 zinc efflux active transmembrane transporter activity -no direct annotations

• [x] tickets made for new is_a rels for GO:0015503 & GO:0015341
• [ ] obsolete

---

-is_a GO:0008504 monoamine transmembrane transporter activity -has direct EXP annotations, all to SLCs - so could either leave, move under 'carrier' and/or rename to monoamine transmembrane carrier activity

• [ ] action TBD

---

-is_a GO:0015399 primary active transmembrane transporter activity -fine. Defintion includes "Primary energy sources known to be coupled to transport are chemical such as ATP hydrolysis, redox energy and photon energy"

• [x] review GO:0015454 light-driven active monoatomic ion transmembrane transporter activity to see if it should be housed under this parent

---

-is_a GO:0008982 protein-N(PI)-phosphohistidine-sugar phosphotransferase activity

• [x] ticket to move under group translocator activity

---

-is_a GO:0090563 protein-phosphocysteine-sugar phosphotransferase activity

• [x] ticket to move under group translocator activity

---

-is_a GO:0015291 secondary active transmembrane transporter activity

• [ ] review children
• [ ] rename to transmembrane carrier activity

---

-is_a GO:0015576 sorbitol transmembrane transporter activity leave this floating, similar to others like this e.g. mannitol TMT, so when parent gone will not have active transport grouping

[pgaudet]

So, according to @amandamackie 's comment, would could consider merging Uniporter and Channel?

https://github.com/geneontology/go-annotation/issues/5208#issuecomment-2301283913

[sjm41]

would could consider merging Uniporter and Channel?

@hattrill what do you think of that proposal? Our current defs state that channel activity is energy-independent, whereasuniporter activity is a child of "secondary active transmembrane transporter activity" (to be renamed "transmembrane carrier activity") whose def says "driven by a chemiosmotic source of energy, not direct ATP coupling"

id: GO:0015292 name: uniporter activity def: "Catalysis of the transport of a single molecular species across a membrane; transport is independent of the movement of any other molecular species." [GOC:mtg_transport, ISBN:0815340729, PMID:10839820] synonym: "facilitated diffusion carrier" EXACT [] synonym: "single-species transporter activity" EXACT [] synonym: "uniport" RELATED [] is_a: GO:0015291 ! secondary active transmembrane transporter activity

id: GO:0015267 name: channel activity def: "Enables the energy-independent facilitated diffusion of a solute through a transmembrane aqueous pore or channel. Stereospecificity is not exhibited but this transport may be specific for a particular molecular species or class of molecules." [GOC:mtg_transport, ISBN:0815340729] synonym: "alpha-type channel activity" RELATED [] synonym: "channel-forming toxin activity" RELATED [] synonym: "channel/pore class transporter activity" EXACT [] synonym: "nonselective channel activity" EXACT [] synonym: "pore activity" BROAD [] synonym: "pore class transporter activity" RELATED [] synonym: "substrate-specific channel activity" RELATED [] xref: TC:1 is_a: GO:0022803 ! passive transmembrane transporter activity

[sjm41]

Here's a specific example of where we have distinct uniporter vs channel terms for the same chemical:

id: GO:0022818 name: sodium ion uniporter activity def: "Catalysis of the active transport of a sodium ion across a membrane by a mechanism involving conformational change, where energy for active transport is derived from membrane potential if the solute is charged." [GOC:mtg_transport, ISBN:0815340729] intersection_of: GO:0022810 ! membrane potential driven uniporter activity intersection_of: has_primary_input CHEBI:29101 ! sodium(1+)

id: GO:0005272 name: sodium channel activity def: "Enables the energy-independent facilitated diffusion of a sodium ion through a transmembrane aqueous pore or channel." [GOC:BHF, GOC:mtg_transport, GOC:pr, ISBN:0815340729] intersection_of: GO:0015267 ! channel activity intersection_of: has_primary_input CHEBI:29101 ! sodium(1+) relationship: part_of GO:0035725 ! sodium ion transmembrane transport

[pgaudet]

Would you be OK with merging these?

[sjm41]

Well, the definitions do appear different. But looking at annotations, I see "sodium ion uniporter activity" has 0 annotations and "sodium channel activity" has 253 EXP annotations. Not sure if that helps decide.... Helen knows more about this than I do!

[sjm41]

FYI, it's a similar situation for these two terms:

id: GO:0022819 - 0 annotations name: potassium ion uniporter activity def: "Catalysis of the active transport of a potassium ion across a membrane by a mechanism involving conformational change, where energy for active transport is derived from membrane potential if the solute is charged." [GOC:mtg_transport, ISBN:0815340729] intersection_of: GO:0022810 ! membrane potential driven uniporter activity intersection_of: has_primary_input CHEBI:29103 ! potassium(1+)

id: GO:0005267 - 840 EXP annotations name: potassium channel activity def: "Enables the energy-independent facilitated diffusion of a potassium ion through a transmembrane aqueous pore or channel." [GOC:BHF, GOC:mtg_transport, GOC:pr, ISBN:0815340729] is_a: GO:0005261 ! monoatomic cation channel activity is_a: GO:0015079 ! potassium ion transmembrane transporter activity intersection_of: GO:0015267 ! channel activity intersection_of: has_primary_input CHEBI:29103 ! potassium(1+) relationship: part_of GO:0071805 ! potassium ion transmembrane transport

[hattrill]

Hi @sjm41 @pgaudet we should definitely not merge uniporter and channels as they are not the same thing - uniporters are carriers and channels are channels.

I do think that the two examples that @sjm41 lists:potassium ion uniporter activity and sodium ion uniporter activity that these terms should be obsoleted - I know of no examples where these ions are transported by a carrier that does not involve the coupled transport of another ion or solute.

[sjm41]

Also tweak these term names: sodium channel activity -> sodium ion channel activity potassium channel activity -> potassium ion channel activity ?