GO:0005487 - nucleocytoplasmic transporter activity parent

[ValWood]

GO:0005487 nucleocytoplasmic transporter activity is a "molecular carrier activity"

not "protein transporter activity"

see https://github.com/geneontology/go-ontology/issues/14331 https://github.com/geneontology/go-ontology/issues/14221

[pgaudet]

Hi Val,

Are you requesting the parent to be changed ?

[ValWood]

yes this branch (GO:0005487 - nucleocytoplasmic transporter activity and children) belongs under carrier.

As you pointed out GO:0005487 - nucleocytoplasmic transporter activity is not a good name.

The children are called import receptors and export receptors.

I think you could rename it "nulceocytoplasmic carrier"

GO:0090631    pre-miRNA transporter activity and GO:0061717    miRNA transporter activity

will also need to be addressed.

but I don't think the terms should be created yet (at least from these papers). They do not indicate whether miRNAs use the same karyopherins as other RNAs in which case I'm not sure these specific terms are required.

All the papers says is that Exportin-t mutant does not affect miRNA export?

[ValWood]

nucleocytoplasmic carrier https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536896/ https://www.ncbi.nlm.nih.gov/pubmed/?term=%22nucleocytoplasmic+carrier%22

would be a good name...

[ValWood]

Hmm a problem. In addition to kayopherins, nucleocytoplasmic transporter has been used quite a lot for "nuclear pore " proteins by SGD.

I would not call the nuclear pore a transporter.... but I don't know what it's function would be. It enables transport, but it isn't a transporter itself is it?

[pgaudet]

TCDB puts the nuclear pore with other pores. So maybe these are OK under transporter activity, and the kayopherins are carriers ?

[ValWood]

OK, people do refer to the pore itself as a "transporter" sometimes. I found 2 egs http://www.ks.uiuc.edu/Research/npc/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944363/

So, transporter and transmembrane transporter can't be merged... The nuclear pore isn't a transmembrane transporter.

[pgaudet]

HI @ValWood I am closing this one. Nucleocytoplasmic transporter activity is now directly under transporter activity, with sibling transmembrane transporter activity. I think this resolves the issue; reopen if not.

[ValWood]

I still think this is a problem. This is the term that we use for nuclear import receptors. I think in the refactoring these are a type of "carrier". However, I'm sure this is covered by other tickets. If I can find one I'll link to this and re-close.

[pgaudet]

@thomaspd suggests this clarification: A transporter does not move with its cargo A carrier moves something by moving itself.

Would that clarify the issue ?

[ValWood]

It would, if you make it clear that the "carrier moves" but does not "self-propel" .

[ValWood]

Also this is not completely true for the Acyl-carrier proteins. Here, only the swinging arm moves.

or possibly for the things that "insert" things into membranes. I don't know if all of these move, but they are classed as carriers.

[ValWood]

GO:0140132 iron-sulfur cluster carrier activity

does this "move" things @Antonialock ?

or just transfer them? (acts as a chaperone)

[pgaudet]

Suggestion following discussion with @ValWood

• 'miRNA transporter activity'

• 'nuclear export signal receptor activity'

• 'nuclear import signal receptor activity'

• 'pre-miRNA transporter activity' -> move under molecular carrier activity. Redefine t make it clear that they represent the karyopherin-like activities

• 'nucleocytoplasmic transporter activity' -> redefine to make it clear that it represents the pore.

[ValWood]

I'm but I'm a bit worried about changing the existing term, and I'm not convinced about an activity for the nuclear pore...it's really only structural and binds to things being moved through it.

I would probably only annotate to "structural component of nuclear pore" GO:0017056 structural constituent of nuclear pore

or "protein binding" part_of "nucleocytoplasmic transport" for components of the pore which are "docking sites"

[Antonialock]

GO:0140132 iron-sulfur cluster carrier activity does this "move" things @Antonialock ?

Hmm, good question, we haven't annotated to that term. I annotated to transferase when I should have annotated to carrier. I'll sort this out today. The carriers move with the clusters. You also have transferases that transfer clusters between carriers -> final acceptor, or carrier -> carrier

[ValWood]

so can you describe what the specific "carrier activity" is here? is it moving with something?

v

[pgaudet]

yes - carriers move with their cargo.

• [x] nucleocytoplasmic transporter activity -> move under 'molecular carrier activity'
• [x] changed definition from 'Enables the directed movement of substances between the nucleus and the cytoplasm of a cell.' to 'Carries substances between the nucleus and the cytoplasm of a cell by moving along with the target protein.'

@ValWood @thomaspd does that look to you ?

[pgaudet]

https://github.com/geneontology/go-ontology/pull/14702

[ValWood]

It looks OK to me as that was the original intent of the import and export carrier grouping term nucleocytoplasmic transporter activity but because it wasn't well defined, it has been used for nuclear pore proteins, will need annotation review.

I suggest nucleocytoplasmic transporter activity rename nucleocytoplasmic importin/exportin activity or similar

[pgaudet]

@rachhuntley I would like to merge GO:0061717 miRNA transporter activity GO:0090631 pre-miRNA transporter activity since the only EXP annotation on these two terms is EXPORTIN5, ie the 'normal' export receptor.

Is this OK for you ?

Thanks, Pascale

[rachhuntley]

Hi Pascale,

So we originally (https://github.com/geneontology/go-ontology/issues/11939) created two terms here because in plants most of the miRNA processing occurs in the nucleus, therefore plants do not transport pre-miRNA but they transport the miRNA duplex (see http://wiki.geneontology.org/index.php/MicroRNA_GO_annotation_manual#Plant_miRNA_biogenesis_and_action).

I would expect the Hasty protein to be annotated to miRNA transporter activity.

I guess the terms could be merged with the primary name as miRNA transporter activity and pre-miRNA transporter activity as a synonym, but I'm not sure if Hasty has the same mechanism as Exportin-5. Both Hasty and XPO5 bind Ran, so it probably does.

Copying @tberardini for her input.

Thanks, Rachael.

[pgaudet]

Hi @rachhuntley @tberardini This seems to be the same molecular function; I suggest that the difference be captured at the BP level, for eg: GO:0061716 miRNA export from nucleus

Would that work ?

Thanks, Pascale

[rachhuntley]

It seems fine to me. Thanks, Rachael.

[pgaudet]

Hello,

Here's the latest proposal on this:

1. nucleocytoplasmic transporter activity is_a 'transporter activity' Definition: Enables the transfer of a substance from one side of the nuclear envelope to the other. Comment: Note that this term is meant to be used for nuclear pore proteins. For importins and exportins, consider 'nuclear import signal receptor activity' or 'nuclear export signal receptor activity'.

2. Change definition of 'transporter activity': Enables the directed movement of substances (such as macromolecules, small molecules, ions) into, out of or within a cell, or between cells. A transporter is in a fixed location in the cell and allows molecules to pass via a channel or a pore in its structure. (text in bold is new)

3. new term: 'nucleocytoplasmic carrier activity' is_a molecular carrier activity Definition: Carries substances between the nucleus and the cytoplasm of a cell by moving along with the target protein. do_not-annotate

4. Added two children:

   • nuclear export signal receptor activity; related synonym: exportin
   • nuclear import signal receptor activity; related synonym: importin

---

@ValWood @thomaspd

• anyone else does that seem OK ?

Thanks, Pascale

[tberardini]

Note that there is an IMP annotation to 'pre-miRNA export from nucleus' for HST from UniProt. I agree with @rachhuntley that this should be 'miRNA export from nucleus' but I cannot edit that annotation. I have removed the TAS annotation made by TAIR to the 'pre-miRNA' term and replaced it with an IMP annotation to 'miRNA export from nucleus' from a different paper.

[rachhuntley]

Thanks Tanya, I'll send an update request to UniProt about the HST annotation.

[ValWood]

I think this works. I'm still a bit leery of annotating all nuclear pore proteins as "nucleocytoplasmic transporter activity" , but the arrangement does work and is much clearer than it was. Even though the term was used incorrectly based in it's intended meaning as a grouping term for importins and exportins, now it is moved out as a parent term, its remaining direct annotations appear to be correct for the new meaning. So, somehow it seemed to work OK!

[bmeldal]

Still to fix:

• [ ] GO:0005215 transporter activity has NARROW synonym "carrier" - should that be removed?

• [ ] "protein import into nucleus" vs "nuclear import" These 2 terms need a tightening of the definition. It suggests that "protein import into nucleus" is_a "nuclear import" when the former refers to the nuclear pore and the latter includes importins. They also have very similar children, some are the same.

• GO:0051170 nuclear import Definition: The directed movement of substances into the nucleus. Synonyms: substance nuclear import | exact single organism nuclear import | exact single-organism nuclear import | related import into nucleus | exact nucleus import | exact is_a GO:0006913 nucleocytoplasmic transport Definition: The directed movement of molecules between the nucleus and the cytoplasm.

• [ ] Suggested Comment: "Use this term to annotate proteins/substances that move through the nuclear pore, such as importins. For nuclear pore proteins consider GO:0015031 protein transport and its children." [or something in that direction]

• GO:0006606 protein import into nucleus Definition: The directed movement of a protein from the cytoplasm to the nucleus. Synonyms: protein nucleus import | exact protein transport from cytoplasm to nucleus | exact protein import into cell nucleus | exact establishment of protein localization to nucleus | exact is_a GO:0015031 protein transport Definition: The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.

• [ ] Suggested Comment: "This term is mean to be used to annotate nuclear pore protein. For importins/exporting consider GO:0006913 nucleocytoplasmic transport and its children." [or something in that direction]

• [ ] I think most of the children need to be moved to GO:0051170 nuclear import.

The only real clue is on the activity term: GO:0005487 nucleocytoplasmic transporter activity Definition: Enables the transfer of a substance from one side of the nuclear envelope to the other. PMID:25802992 Comments: Note that this term is meant to be used for nuclear pore proteins. For importins and exportins, consider 'nuclear import signal receptor activity' or 'nuclear export signal receptor activity'.

Same applies to

• [ ] GO:0051168 nuclear export Definition: The directed movement of substances out of the nucleus. and

• [ ] GO:0006611 protein export from nucleus Definition: The directed movement of a protein from the nucleus into the cytoplasm.

• [ ] There are also many equivalent relationships for the export and import terms that are missing in the respective opposite term. See figure:

3.

• [ ] obsolete GO:0042564 NLS-dependent protein nuclear import complex and GO:0006607 NLS-bearing protein import into nucleus?

In https://github.com/geneontology/go-annotation/issues/1700 I asked: "Should GO:0042564 NLS-dependent protein nuclear import complex (A dimer consisting of an alpha and a beta-subunit that imports proteins with an NLS into the nucleus through a nuclear pore.) have "importin" as a narrow synonym?" Val says "Personally I don't think it's a different process....Some things might not have NLS but they are imported with something that has.... I don't think "NLS-dependent" needs to be a term....Isn't all nucleocytoplasmic transport NLS dependent, its just that only sometimes is the NLS identified...."

Of course, I might be completely wrong here!

[ValWood]

Re comment "protein import into nucleus" vs "nuclear import" These 2 terms need a tightening of the definition. It suggests that "protein import into nucleus" is_a "nuclear import" when the former refers to the nuclear pore and the latter includes importins. They also have very similar children, some are the same."

reply: "protein import into nucleus" vs "nuclear import" should be a parent child relationship. I don't know if separate terms are needed. This was to historically distinguish between protein and non protein cargo. Both terms can refer to importins, or the nuclear pore (some nuclear pore proteins appear to be required for import specificity)

2017-12-08	Deleted	RELATION	is a GO:0051170 (nuclear import)

should be added back

[ValWood]

see https://github.com/geneontology/go-ontology/issues/14748

[pgaudet]

@ValWood Is this fixed ?

[ValWood]

I think it is OK. I'm still not completely comfortable with the classification of the nuclear pore as a "transporter". I still think it only "enables" transport, and is not a transporter per se. However, it is clear that this term is only for nuclear pore proteins, and how to annotate importins and exportins, which are in the carrier branch so can be closed.

[bmeldal]

Don't we have to fix the defs? As it is now it's not clear what applies to NP proteins and what's for importins and exportins - without reading this thread.

[ValWood]

nucleocytoplasmic carrier activity Definition (GO:0140142) Carries substances between the nucleus and the cytoplasm of a cell by moving along with the target protein. Restrictions This term should not be used for direct annotation.

1. I'm not sure we always know if an importin is for import or export if from sequence similarty?

2. The children are defined Combining with a nuclear import signal (NIS) to mediate transport of a NIS-containing protein through the nuclear pore, from the cytoplasm to the nucleus. PMID:25802992

perhaps the definition of the parent could be

Combining with a nuclear import signal (NIS) or (NES) to mediate transport of a protein through the nuclear pore, by moving with the target protein. PMID:25802992

I still think the name of GO:0005487 JSON nucleocytoplasmic transporter activity for nuclear pore proteins should be changed.

The community refer to karyopherins as "nucleocytoplasmic transporters" not the nuclear pore itself. i.e. "importin family of nucleocytoplasmic transporters". I have never heard this term used to describe the nuclear pore....

I don't know what I would name it to though....

[bmeldal]

I don't have more insight than what I said above or what Val said.

Although one point: the NIS is very often called a NLS = nuclear localisation signal, so this should at least be a synonym for the relevant terms.

[pgaudet]

@bmeldal

1. GO:0005215 transporter activity has NARROW synonym "carrier" - should that be removed? I think that should stay, because some transmembrane transporters (such as the SCL*) are named carriers.

[ValWood]

Should it be related in that case?

[bmeldal]

ok, "carrier" term as RELATED and add some comment to explain to the user how to distinguish btw carrier and transporter.

[pgaudet]

• Renamed 'nucleocytoplasmic transporter activity' to 'nuclear pore activity' and added to the definiton, "Enables the transfer of a substance across the nuclear envelope by providing a protein-lined channel in the nuclear envelope."
• add 'part of' some 'nucleocytoplasmic transport' to 'nucleocytoplasmic carrier activity'
  • add a comment to 'transporter activity' "Some transporters, such as certain members of the SLC family, are referred to as 'carriers'; however GO uses carrier with a different meaning: a carrier binds to and transports the substance, whereas a transporter forms some pore that allows the passing of molecules. " @bmeldal is this OK with you ?

Thanks, Pascale

[bmeldal]

GO:0005215 transporter activity:

• I think we should make "carrier" RELATED synonym as suggested above.
• Can you refer to the parent term for carriers in the comment? E.g. GO:0140104 molecular carrier activity?

Thanks, Birgit

[pgaudet]

Thanks @bmeldal

• the synonym is 'related', indeed
• fixed the comment as follows: 'Some transporters, such as certain members of the SLC family, are referred to as 'carriers'; however GO uses carrier with a different meaning: a carrier binds to and transports the substance (see GO:0140104 molecular carrier activity), whereas a transporter forms some pore that allows the passing of molecules.'

Thanks, Pascale

[pgaudet]

Note to self: look for a better term label. Structural component of the nuclear pore ?

[rachhuntley]

Hi, I'm just looking at correcting annotations with the do_not_annotate term 'nucleocytoplasmic carrier activity' and it looks like there are no suitable replacement terms. I want to indicate that RAN and XPO5 are exporting pre-miRNAs from the nucleus. I have made the distinction for pre-miRNA with a process term, as we agreed above, but there is no suitable function term.

The term has the narrow synonyms miRNA and pre-miRNA transporter activity, but is do_not_annotate and its definition refers to moving target proteins. The child terms are not suitable either as there is no nuclear export signal, as traditionally defined (short amino acid sequence of 4 hydrophobic residues in a protein). The pre-miRNAs bind exportin-5 through small RNA hairpins bearing 2-nt 3′ overhangs. Should I be using the less specific term 'molecular carrier activity' and indicating the miRNA in the extension, or should we have a new, more specific term as a sibling to the NES terms that describes the pre-miRNA export mechanism?

I also don't think the comment associated with 'nucleocytoplasmic carrier activity' is sufficient - it refers to the (long) GitHub issue where the changes were made, so it's not easy to see what other terms you should be using instead.

[ValWood]

Term defs should be relaxed to include ncRNAs. GO:0140142 nucleocytoplasmic carrier activity GO:0061608 nuclear import signal receptor activity GO:0005049 nuclear export signal receptor activity

[rachhuntley]

But it should also be made clear that a nuclear export signal can include a short amino acid sequence of 4 hydrophobic residues in a protein (for protein export) or small RNA hairpins bearing 2-nt 3′ overhangs (for pre-miRNA export). I'm not sure if there are other types of NES?

[deustp01]

Trying to remember from a long time ago, it looks like two distinct processes may be getting lumped together in the discussion here. One is the assembly of a cargo package for movement from the cytosol into the nuclear or vice versa. The other is the process of moving that cargo through the nuclear pore, and the term that started this discussion, GO:0005487 "nucleocytoplasmic transporter activity" (now a secondary term under GO:0017056 "structural constituent of nuclear pore") applies only to the second process. And, if I understand GO usage correctly, GO:0005487 / GO:0017056 should only be used to annotate the proteins involved in mediating cargo movement, not proteins in the cargo (where that includes adapters like exportins as well as cargo proper). @ukemi ?

[ValWood]

@deustp01 following up

GO:0005487 / GO:0017056 are both IDs for "structural constituent of nuclear pore"

For importins and exportins, we would use 'GO:0061608 nuclear import signal receptor activity' or 'GO:0005049 nuclear export signal receptor activity', respectively (now classed as "molecular carrier/ nucleocytoplasmic carrier activity"

we don't annotate the cargo to these terms.

val

[pgaudet]

• To be clear: GO:0005487 has been merged into GO:0017056 "structural constituent of nuclear pore"

• @deustp01 : "the assembly of a cargo package for movement from the cytosol into the nuclear or vice versa" is binding to the nuclear import signal receptor (GO:0061608) or nuclear export signal receptor activity (GO:0005049)

• to address @rachhuntley 's point, how about updating the definitions as follows: GO:0061608: nuclear import signal receptor activity: "Combining with a nuclear import signal (NIS) on a cargo to be transported, to mediate transport of the cargo through the nuclear pore, from the cytoplasm to the nucleus. The cargo can be either a RNA or a protein." GO:0005049 nuclear export signal receptor activity: "Combining with a nuclear export signal (NES) on a cargo to be transported, to mediate transport of a the cargo through the nuclear pore, from the nuclear to the cytoplasm. The cargo can be either a RNA or a protein."

@rachhuntley Can you provide some reference for RNA import and export ?

Thanks, Pascale

[pgaudet]

@rachhuntley Can you provide some reference for RNA import and export ?

Actually the current reference for import described RNA !!!

[pgaudet]

Also updated x references:

• nuclear export: PMID:11743003, PMID:25802992, PMID:28713609, Wikipedia:Nuclear_transport
• nuclear import: PMID:28713609, Wikipedia:Nuclear_transport