MF transport terms for FG-nucleoporins? for Karyopherins?

[gocentral]

I'm currently working on updating SGD's GO annotations for the nuclear pore proteins and am a bit stuck on assigning function to the "FG nucleoporins". These are the group of proteins that line the core of the nuclear pore and are responsible, along with karyopherins (aka nuclear transport receptors), for the selective transport of large molecules/complexes into and out of the nucleus. The molecular details are a bit fuzzy. Here are a couple of recent mini-reviews on the subject:

PMID: 19801417 PMID: 20947011

Right now, most groups seem to annotate the FG nucleoporins to "nucleocytoplasmic transporter activity" (GO:0005487). I haven't looked quite as carefully at the karyopherin annotation, but it looks like these are often annotated to substrate-specific transport terms such as protein transporter activity (GO:0008565) or it's children.

It seems to me that "nucleocytoplasmic transporter activity" isn't quite right for FG nucleoporin, especially since it looks like it's interaction between the karyopherins and FG nucleoporins that does the transport (although the FG nucleoporins alone are responsible for the barrier to transport).

Would it be appropriate to make function terms for FG-nucleoporin activity and nuclear transport receptor activity, as children of nucleocytoplasmic transport?

Reported by: diannafisk

Original Ticket: geneontology/ontology-requests/8424

[gocentral]

Ten years ago (last I was paying careful attention), the view was that the overall transport process required both kinds of molecules: karyopherin proteins associated with a cargo complex interact with components of the nuclear pore complex to make something happen (the fuzzy molecular details were fuzzy then, too) that enables the cargo complex to traverse the pore, so the two kinds of proteins, nucleoporins and karyopherins, can be assigned tow distinct functional roles in the overall transport process and that could justify the use of two different MF terms.

Given the molecular fuzziness, is a term like "receptor" perhaps too specific to describe nucleoporin function?

Peter

Original comment by: deustp01

[gocentral]

Thanks for the input Peter!

Yep, the view is still that the overall transport process requires FG-nups and Karyopherins. There have even been some crazy in vitro experiments that were able to reconstitute "transport" with just an FG-nup and a Karyopherin.

"Nuclear transport receptor" seems to be the generic term for karyopherins/importins/exportins/transportins. It's not particularly descriptive of the function, since these proteins are more transporters than receptors, to my mind. I have to read up some more on the karyopherins (my focus has been on the FG-nups), but I'm under the impression that their role is better characterized than that of the FG-nups. My vague understanding is that the Karyopherins interact directly with the substrate and the karyopherin-substrate complex gets transported through the barrier formed by the FG-nups. Somehow (and this is where it gets real fuzzy - is that barrier a "mesh"? is it a "gel"? is it "brushes in constant motion"?) the interaction between the substrate-bound karyopherin and the FG-nup(s) causes a change in the FG-nup barrier such that transport is allowed. My favorite theory of how this works (mostly because it's the only one I can actually wrap my head around) is that interaction between the karyopherin and the natively unstructured FG-nup gel, induces the FG-nups to arrange into channels just the right size for the karyopherin+cargo to get through. But there are other hypotheses.

I'll have to really work at decent descriptions for both these functions, since neither of them is an easy-to-describe catalytic activity. But, they seem like genuine, distinct functions to me and it sounds like you concur.

Anybody else have a different or more articulate grasp on how these things work?

Thanks!

-Dianna

Original comment by: diannafisk

[gocentral]

Hi,

The previous transportin, importune and exportin terms (GO:0005649, GO:0005646 and GO:0005651) were cellular component terms and were obsoleted because they weren't describing a complex.

I agree that calling the karyopherins 'receptors' could be confusing.

Would it perhaps be better/easier to distinguish these two roles with process terms?

E.g.

karyopherin: nucleocytoplasmic transport, substrate recognition ; GO:NEW

And the function would be x binding (where x is the substrate they're transporting).

nucleoporin: nucleocytoplasmic transport, nuclear pore rearrangement ; GO:NEW (I'm sure we could come up with better wording)

? thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

There is a function term for some karyopherins importin-alpha export receptor activity but this is restrictive because it is under protein transporter activity, so cannot be used for importins (karyopherins ) which transport RNAs I could only find this one, although I though there were others.....

There is also a component term for the "docking" nucleoporins: karyopherin docking complex so maybe "karyopherin docking activity" or similar would be a suitable name? (under binding?)

val

Original comment by: ValWood

[gocentral]

Val, the GO term you mention is a transporter (exporter) FOR importin-alpha, and acts to recycle importin back to the cytoplasm:

importin-alpha export receptor activity ; GO:0008262 Interacting selectively and non-covalently with importin-alpha to mediate its transfer through the nuclear pore to the cytoplasm.

We already have a process term for 'docking' in transport. It's not overly clear (to me at least) if both nucleoporins and karyopherins can be annotated with the term... protein import into nucleus, docking ; GO:0000059 A protein complex assembly process that contributes to protein import into the nucleus, and that results in the association of a cargo protein, a carrier protein such as an importin alpha/beta heterodimer, and a nucleoporin located at the periphery of the nuclear pore complex.

Are the part_of children of the process term 'protein import into nucleus ; GO:0006606' enough to distinguish the nucleoporins and karyopherins, or are MF terms (or further children of GO:6606) still required?

We have: protein import into nucleus, docking ; GO:0000059 (BP) protein import into nucleus, translocation ; GO:0000060 (BP) protein import into nucleus, substrate release ; GO:0000061 (BP)

Becky

Original comment by: rebeccafoulger

[gocentral]

Uh oh, you are right importin-alpha export receptor activity ; GO:0008262 is indeed defined as a receptor for the importin... Although it has occasionally been used to annotate the nuclear pore proteins which bind importins e.g.

CSE1 Nuclear envelope protein that mediates the nuclear export of importin alpha (Srp1p),

It has also been used to annotate karyopherins , importins and exportins themselves:

MSN5 Karyopherin involved in nuclear import and export of proteins (plus a whole bunch of IEA mappings)

This term probably needs renaming, and most of the annotations/mappings need removing....

Val

Original comment by: ValWood

[gocentral]

Sorry, all, I was out sick and got a little bit behind. Thanks for all the feadback!

First, I do think that we need function terms to describe these classes of proteins. If anything, they should have the same process terms, with different functions.

GO currently has a Molecular function term nucleocytoplasmic transporter activity (GO:0005487), which has been used by many groups for FG-Nups. My feeling is that this term is a bit bogus as anything but a grouping term, since nucleocytoplasmic transport is really a process that requires two distinct functions, those of FG-proteins and those of Karyopherins. Am I thinking about this correctly?

Again, I'm particularly coming at this from the view of trying to find an appropriate function term for FG-nucleoporins. These proteins have a real, specific function (not "structural" or "unknown"), it's just hard to describe clearly because it's not a classical catalytic function like "binding".

Right now the terms that have been used for most kayopherins (protein transporter activity, mRNA transporter activity, etc.) are reasonable in terms of substrate-function, but don't trace up to "nucleocytoplasmic transporter activity." So, maybe we should make some specific child terms here?

I know that there was a transport reorg. sometime back, and I'm not exactly sure how it considered location-specific terms, like "nucleocytoplasmic". Anybody remember? Or know where the documentation is? (I poked around, but couldn't find any. But that could be just my own back detective skills.)

It's been a long time since I've done anything complicated with GO terms, so I wanted to make sure I wasn't completely off my rocker before putting time into an explicit proposal. It sounds like this is a generally acceptable idea, so I'll go ahead hash out an explicit proposal for these function terms and come back with it in a week or so. OK?

Thanks!

-Dianna

Original comment by: diannafisk

[gocentral]

Hi Dianna,

Hope you're feeling better! At the moment, GO is describing the different roles by splitting up the process of 'protein import' into the separate steps: protein import into nucleus, docking ; GO:0000059 protein import into nucleus, translocation ; GO:0000060 protein import into nucleus, substrate release ; GO:0000061

If you can come up with separate 'activities' that can be assigned to nucleoporins and karyopherins though, that would be great- thanks.

For your other questions, Jen put up some wiki documentation on the transporter work at: http://gocwiki.geneontology.org/index.php/Transporters. There's a bit of the nuclear pore not being considered trans-membrane, but I think the work dealt more with transporters (which are largely catergorized based on what they transport) rather than the process of transporting from one location to another.

thanks, Becky

Original comment by: rebeccafoulger

[gocentral]

Hi All,

This took a bit longer than I anticipated, but here's my proposal for expanding the "nucleocytoplasmic transporter activity" branch of the MF ontology. In this scheme, the FG-nucleoporins would be annotated to "karyopherin docking activity" and/or "permeability barrier activity." Karyopherins (aka importins, exportins, transportins, etc.) would be annotated to one of the substrate-specific nucleocytoplasmic transporter activity terms. I added the substrate-specific terms that I knew I needed, from a pretty quick survey of karyopherins - we may need to add more later. I also ended up adding some substrate-specific parent terms that didn't already exist (hopefully I got them all). I've included examples from S. cerevisiae for all the new leaf terms.

I'm not sure exactly whether or not these new terms should also have some relationship with "protein binding" (or other appropriate substrate binding term)? Most of the transport function terms don't seem to have any relationship with a "binding" term, but I'm not sure if that was intentional or not. The karyopherins do definitely bind their substrates during transport. Karen Christie suggested that a "has_part" relationship might be appropriate? But we weren't absolutely sure if this was correct. I've included that relationship, below, but I'm not married to the idea. Please let me know if this is a good idea or a bad one!

Also note that I'm proposing a clarification of the definition and term name for GO:0008262. As Val pointed out earlier, this term is currently very confusing and has been misused.

Thanks,

-Dianna

GO:0017056 structural constituent of nuclear pore NEW:001 permeability barrier activity: Providing a semi-permeable barrier within the central core of the nuclear pore. This selective barrier allows passive diffusion of small molecules and facilitated diffusion of karyopherin-cargo complexes. Examples include the FG-nucleoporins in eukaryotes such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:17418788, PMID:19680227, PMID:19098896, reviewed in PMID:19801417)

GO:0005487 nucleocytoplasmic transporter activity NEW:002 karyopherin docking activity: Interacting selectively and non-covalently with a nucleocytoplasmic transporter, such as a karypherin or a karyopherin-cargo complex, in order to facilitate transport through the nuclear pore. Examples include the FG-nucleoporins, such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:12917401, PMID:11387327 , PMID:17875746, reviewed in PMID:19801417) NEW:003 RNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an RNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae NEW:004 mRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an mRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include MEX67 in S. cerevisiae NEW:005 tRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a tRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include LOS1 in S. cerevisiae NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a ribonucleoprotein complex to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae NEW:007 protein nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a protein to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. GO:0008262 importin-alpha recycling activity: Interacting selectively and non-covalently with importin-alpha to mediate its transfer from the nucleus, through the nuclear pore, to the cytoplasm. Examples include CAS in drosophila and CSE1 in S. cerevisiae. NEW:008 Ran-GDP recycling activity: Interacting selectively and non-covalently with Ran-GDP to mediate its transfer from the cytoplasm, through the nuclear pore, to the nucleoplasm. Examples include NTF2 in S. cerevisiae

GO:0022892 substrate-specific transporter activity NEW:009 RNA transporter activity: Enables the directed movement of RNA into, out of or within a cell, or between cells. GO:0051033 RNA transmembrane transporter activity NEW:003 RNA nucleocytoplasmic transporter activity NEW:004 mRNA nucleocytoplasmic transporter activity NEW:005 tRNA nucleocytoplasmic transporter activity NEW:010 mRNA transporter activity: Enables the directed movement of mRNA into, out of or within a cell, or between cells. NEW:004 mRNA nucleocytoplasmic transporter activity NEW:011 tRNA transporter activity: Enables the directed movement of tRNA into, out of or within a cell, or between cells. GO:0051034 tRNA transmembrane transporter activity NEW:005 tRNA nucleocytoplasmic transporter activity NEW:012 ribonucleoprotein complex transporter activity: Enables the directed movement of ribonucleoprotein complexes into, out of or within a cell, or between cells NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity GO:0008565 protein transporter activity GO:0008320 protein transmembrane transporter activity NEW:007 Protein nucleocytoplasmic transporter activity GO:0008262 importin-alpha recycling activity. NEW:008 Ran-GDP recycling activity

GO:0005515 protein binding has_part NEW:007 protein nucleocytoplasmic transporter activity has_part NEW:002 karyopherin docking activity GO:0003723 : RNA binding has_part NEW:003 RNA nucleocytoplasmic transporter activity GO:0003729 : mRNA binding has_part NEW:004 mRNA nucleocytoplasmic transporter activity GO:0000049 : tRNA binding has_part NEW:005 tRNA nucleocytoplasmic transporter activity GO:0043021: ribonucleoprotein binding has_part NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity

Original comment by: diannafisk

[gocentral]

Ack - sorry! Lost the indenting. Sorry! Here it is again, with the indenting to make the relationships clear. All the relationships are is_a, unless otherwise specified.

-Dianna

GO:0017056 structural constituent of nuclear pore NEW:001 permeability barrier activity: Providing a semi-permeable barrier within the central core of the nuclear pore. This selective barrier allows passive diffusion of small molecules and facilitated diffusion of karyopherin-cargo complexes. Examples include the FG-nucleoporins in eukaryotes such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:17418788, PMID:19680227, PMID:19098896, reviewed in PMID:19801417)

GO:0005487 nucleocytoplasmic transporter activity NEW:002 karyopherin docking activity: Interacting selectively and non-covalently with a nucleocytoplasmic transporter, such as a karypherin or a karyopherin-cargo complex, in order to facilitate transport through the nuclear pore. Examples include the FG-nucleoporins, such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:12917401, PMID:11387327 , PMID:17875746, reviewed in PMID:19801417) NEW:003 RNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an RNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae NEW:004 mRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an mRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include MEX67 in S. cerevisiae NEW:005 tRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a tRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include LOS1 in S. cerevisiae NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a ribonucleoprotein complex to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae NEW:007 protein nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a protein to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. GO:0008262 importin-alpha recycling activity: Interacting selectively and non-covalently with importin-alpha to mediate its transfer from the nucleus, through the nuclear pore, to the cytoplasm. Examples include CAS in drosophila and CSE1 in S. cerevisiae. NEW:008 Ran-GDP recycling activity: Interacting selectively and non-covalently with Ran-GDP to mediate its transfer from the cytoplasm, through the nuclear pore, to the nucleoplasm. Examples include NTF2 in S. cerevisiae

GO:0022892 substrate-specific transporter activity NEW:009 RNA transporter activity: Enables the directed movement of RNA into, out of or within a cell, or between cells. GO:0051033 RNA transmembrane transporter activity NEW:003 RNA nucleocytoplasmic transporter activity NEW:004 mRNA nucleocytoplasmic transporter activity NEW:005 tRNA nucleocytoplasmic transporter activity NEW:010 mRNA transporter activity: Enables the directed movement of mRNA into, out of or within a cell, or between cells. NEW:004 mRNA nucleocytoplasmic transporter activity NEW:011 tRNA transporter activity: Enables the directed movement of tRNA into, out of or within a cell, or between cells. GO:0051034 tRNA transmembrane transporter activity NEW:005 tRNA nucleocytoplasmic transporter activity NEW:012 ribonucleoprotein complex transporter activity: Enables the directed movement of ribonucleoprotein complexes into, out of or within a cell, or between cells NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity GO:0008565 protein transporter activity GO:0008320 protein transmembrane transporter activity NEW:007 Protein nucleocytoplasmic transporter activity GO:0008262 importin-alpha recycling activity. NEW:008 Ran-GDP recycling activity

GO:0005515 protein binding has_part NEW:007 protein nucleocytoplasmic transporter activity has_part NEW:002 karyopherin docking activity GO:0003723 : RNA binding has_part NEW:003 RNA nucleocytoplasmic transporter activity GO:0003729 : mRNA binding has_part NEW:004 mRNA nucleocytoplasmic transporter activity GO:0000049 : tRNA binding has_part NEW:005 tRNA nucleocytoplasmic transporter activity GO:0043021: ribonucleoprotein binding has_part NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity

Original comment by: diannafisk

[gocentral]

And, the third attempt at loading the proposal, this time with proper formatting (thanks Becky!)

GO:0017056 structural constituent of nuclear pore --[isa]NEW:001 permeability barrier activity: Providing a semi-permeable barrier within the central core of the nuclear pore. This selective barrier allows passive diffusion of small molecules and facilitated diffusion of karyopherin-cargo complexes. Examples include the FG-nucleoporins in eukaryotes such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:17418788, PMID:19680227, PMID:19098896, reviewed in PMID:19801417)

GO:0005487 nucleocytoplasmic transporter activity --[isa]NEW:002 karyopherin docking activity: Interacting selectively and non-covalently with a nucleocytoplasmic transporter, such as a karypherin or a karyopherin-cargo complex, in order to facilitate transport through the nuclear pore. Examples include the FG-nucleoporins, such as NUP1, NUP100, and NUP49 in S. cerevisiae. (PMID:12917401, PMID:11387327, PMID:17875746, reviewed in PMID:19801417) --[isa]NEW:003 RNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an RNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae ----[isa]NEW:004 mRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with an mRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include MEX67 in S. cerevisiae ----[isa]NEW:005 tRNA nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a tRNA molecule to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include LOS1 in S. cerevisiae --[isa]NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a ribonucleoprotein complex to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. Examples include CRM1 in S. cerevisiae --[isa]NEW:007 protein nucleocytoplasmic transporter activity: Interacting selectively and non-covalently with a protein to mediate its transport into or out of the nucleus. The assistance of a specific adaptor protein may or may not be required. ----[isa]GO:0008262 importin-alpha recycling activity: Interacting selectively and non-covalently with importin-alpha to mediate its transfer from the nucleus, through the nuclear pore, to the cytoplasm. Examples include CAS in drosophila and CSE1 in S. cerevisiae. ----[isa]NEW:008 Ran-GDP recycling activity: Interacting selectively and non-covalently with Ran-GDP to mediate its transfer from the cytoplasm, through the nuclear pore, to the nucleoplasm. Examples include NTF2 in S. cerevisiae

GO:0022892 substrate-specific transporter activity --[isa]NEW:009 RNA transporter activity: Enables the directed movement of RNA into, out of or within a cell, or between cells. ----[isa]GO:0051033 RNA transmembrane transporter activity ----[isa]NEW:003 RNA nucleocytoplasmic transporter activity ------[isa]NEW:004 mRNA nucleocytoplasmic transporter activity ------[isa]NEW:005 tRNA nucleocytoplasmic transporter activity ----[isa]NEW:010 mRNA transporter activity: Enables the directed movement of mRNA into, out of or within a cell, or between cells. ------[isa]NEW:004 mRNA nucleocytoplasmic transporter activity ----[isa]NEW:011 tRNA transporter activity: Enables the directed movement of tRNA into, out of or within a cell, or between cells. ------[isa]GO:0051034 tRNA transmembrane transporter activity ------[isa]NEW:005 tRNA nucleocytoplasmic transporter activity --[isa]NEW:012 ribonucleoprotein complex transporter activity: Enables the directed movement of ribonucleoprotein complexes into, out of or within a cell, or between cells ----[isa]NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity --[isa]GO:0008565 protein transporter activity ----[isa]GO:0008320 protein transmembrane transporter activity ----[isa]NEW:007 Protein nucleocytoplasmic transporter activity ------[isa]GO:0008262 importin-alpha recycling activity. ------[isa]NEW:008 Ran-GDP recycling activity

GO:0005515 protein binding --[has_part]NEW:007 protein nucleocytoplasmic transporter activity --[has_part]NEW:002 karyopherin docking activity GO:0003723 : RNA binding --[has_part]NEW:003 RNA nucleocytoplasmic transporter activity GO:0003729 : mRNA binding --[has_part]NEW:004 mRNA nucleocytoplasmic transporter activity GO:0000049 : tRNA binding --[has_part]NEW:005 tRNA nucleocytoplasmic transporter activity GO:0043021: ribonucleoprotein binding --[has_part]NEW:006 ribonucleoprotein complex nucleocytoplasmic transporter activity

Original comment by: diannafisk

[gocentral]

Hi Dianna,

I feel that some of the suggested function terms are really processes. For example, all the docking terms in GO are processes.

Similarly, 'permeability barrier activity' would be better as a process (similar to the regulation of membrane permeability terms we currently have (E.g. GO:0046902).

Since the role of the karyopherin is to bind to the substrate cargo, these would get 'x binding' terms. I'll look into linking these up to the 'protein import', 'protein export' etc.

I can also add a term for annotation of karyopherins:

term: nuclear pore complex binding ; GO:NEW related synonym: nucleoporin binding Namespace: molecular function is_a: protein complex binding ; GO:0032403 Def: Interacting selectively and non-covalently with the nuclear pore complex….

Becky

Original comment by: rebeccafoulger

[gocentral]

Oh, ack, I haven't thought about this in two months! Let me get back to you with more intelligent comments.

My initial reaction is that your comment doesn't address the function of the FG nucleoporins. Which is the critical piece, for me.

-Dianna

Original comment by: diannafisk

[gocentral]

• assigned_to: nobody --> rfoulger

Original comment by: paolaroncaglia

[gocentral]

Hi again Dianna. We discussed this at our weekly GOEd meeting last week, and reached the following conclusions:

i. Pemeability barrier is a weird term to have in function. We can create a process term: regulation of nuclear membrane permeability.

ii. We could create terms 'x transporter activity involved in nucleocytoplasmic transport' to combine the substrate-specific transporter, and nucleocytoplasmic transporter terms.

iii. Rename 'importin-alpha export receptor activity ; GO:0008262' to be a transporter.

In summary, we thought that, overall, function isn't the best place to capture the role the nucleoporins play in the transport process, and that creating docking process terms would be more consistent with existing terms in GO.

The best way I can think of for creating a nucleoporin function is binding to a karyopherin-cargo complex.

Does that help any?

Original comment by: rebeccafoulger

[gocentral]

• assigned_to: RFoulger --> Paola Roncaglia
• Group: --> None

Original comment by: paolaroncaglia

[gocentral]

Diane from SGD will look into this ticket, as Dianna no longer works there. The first question is - can/should we close this ticket as out of date, or is it still relevant? If so, do we need to create any new term, or add links to existing terms? Please note that the ontology may have changed a bit in the meantime.

Thanks! Paola

Original comment by: paolaroncaglia

[gocentral]

Hi Paola,

I'm looking into this item today and will re-request terms based on the thread later in the day.

Thanks, Diane

Original comment by: dinglis

[gocentral]

Hi Paola,

So it looks like the GO editors decided that a MF term was not warranted but BP terms were appropriate. So the term suggested by Becky will be fine for the time being.

NTR: nuclear membrane permeability NTR via TG: pos/neg/reg of nuclear membrane permeability

The other substrate-transport terms need more investigation. I'll go ahead and open a new ticket if I land up needing them.

Thanks,

Diane

Original comment by: dinglis

[gocentral]

Thanks Diane.

Added new terms: GO:0097605 regulation of nuclear membrane permeability GO:0097606 positive regulation of nuclear membrane permeability GO:0097607 negative regulation of nuclear membrane permeability

Closing now. Paola

Original comment by: paolaroncaglia

[gocentral]

• status: open --> closed-accepted

Original comment by: paolaroncaglia

[gocentral]

is this right? Nucleoplasmic transport is not a form of transmembrane transport (see comment to GO:0006913 nucleocytoplasmic transport), so is it right to make regulation of nuclear pore behavior a kind of regulation of membrane permeability? (Apologies if I've missed the point here.)

Original comment by: deustp01

[gocentral]

• status: closed-accepted --> open

Original comment by: paolaroncaglia

[gocentral]

• Group: None --> SGD

Original comment by: paolaroncaglia

[gocentral]

Marking this ticket for discussion at the SF jamboree.

Summary for self: Terms are needed to annotate proteins that line up the nuclear pore. Remember that nucleocytoplasmic transport (i.e. transport through the nuclear pore complex) is not transmembrane because the nuclear membrane is a double membrane, and is not traversed. The terms I created are GO:0097605 'regulation of nuclear membrane permeability' and children. Peter argues: "is this right? Nucleoplasmic transport is not a form of transmembrane transport (see comment to GO:0006913 nucleocytoplasmic transport), so is it right to make regulation of nuclear pore behavior a kind of regulation of membrane permeability?"

Current ontology structure:

regulation of biological quality ---regulation of membrane permeability ------regulation of lysosomal membrane permeability ------regulation of mitochondrial membrane permeability ------regulation of nuclear membrane permeability

So no link to transmembrane terms. However, def. of membrane permeability terms say: "Any process that modulates the frequency, rate or extent of the passage or uptake of molecules by a membrane.". Would 'permeability' cover transport through the nuclear pore complex? Wikipedia: "The cell membrane is selectively permeable and able to regulate what enters and exits the cell". But would permeability in general cover transport through the nuclear pore complex? Wikipedia again:

"Transport through the nuclear pore complex Small particles (< ~40 kDa) are able to pass through the nuclear pore complex by passive diffusion. Larger particles are also able to pass through the large diameter of the pore but at almost negligible rates. Efficient passage through the complex requires several protein factors. Karyopherins, which may act as importins or exportins are part of the Importin-β super-family which all share a similar three-dimensional structure."

OBA has: membrane permeability = Any measurable or observable characteristic related to the permeability of a membrane. permeability = A structural quality inhering in a bearer by virtue of the bearer's disposition to being permeated or pervaded by a liquid (as by osmosis or diffusion).

Etimology of 'permeability': early 15c., from Late Latin permeabilis "that can be passed through, passable," from Latin permeare "to pass through, go over," from per- "through" (see per) + meare "to pass," from PIE root *mei- (1) "to change" (see mutable). Related: Permeably. (http://www.etymonline.com/index.php?term=permeable)

Based on this, I'd say that yes, 'membrane permeability' could cover nucleocytoplasmic transport. Do others agree? If yes, we'd need to edit the defs. of membrane permeability terms (or add a def. comment) to specify this. If not, we'd need to place nuclear membrane permeability terms elsewhere, and rename them.

Original comment by: paolaroncaglia

[gocentral]

• labels: Other term-related request --> Other term-related request, jamboree, transport

Original comment by: paolaroncaglia

[gocentral]

Hi Peter and Diane,

At the SF jamboree yesterday, we looked carefully into Peter's comment. Here are our conclusions:

The current terms 'regulation of nuclear membrane permeability' and children really refer to permeability (and transport) across the entire nuclear envelope rather than just nuclear membrane. Therefore, I did the following edits:

• renamed (and redefined) 'regulation of nuclear membrane permeability' and children as 'regulation of nuclear envelope permeability' (and children);
• moved 'regulation of nuclear membrane permeability' and placed it directly under 'regulation of biological quality' and 'nuclear envelope organization';
• added link: 'positive regulation of nuclear envelope permeability' positively_regulates 'nucleocytoplasmic transport'.

Closing now, but feel free to comment if you have any concerns. Thanks, Paola

Original comment by: paolaroncaglia

[gocentral]

• status: open --> closed-fixed

Original comment by: paolaroncaglia