split iron-siderophore transport terms from siderophore export from cell

[ValWood]

siderophore (ferritin) needs to be exported before it can be imported as siderophore-iron. Currently, according to the fission yeast expert, despite extensive work the fungal exporter is unknown (but I need to put this in the GO-CAM as a pathway hole). "In bacteria, there are few proteins known for this", (however, I have been unable to locate these in GO annotation and it seems that the fungal exporters are probably not closely related).

Some issues:

1. siderophore-iron transmembrane transporter should be is_a iron chelate transmembrane transporter
2. There is no term to represent the transporter to export siderophore because all the terms involved iron
3. enterobactin is a siderophore
4. Unless these terms specify that they are 'uptake' or iron-siderophore they should not have an import parent
   (should we have uptake in MF or BP I am still unclear on this?)
5. Should 'siderophore uptake transmembrane transporter' be named siderophore-iron uptake transporter?

Basically, I need a term that I can use for export of the ferrichrome siderophore (or just siderophore), but none of the available terms are suitable because they mention uptake, iron, or have an import parent. These all need to be disambiguated. For example, "ferrichrome transmembrane transporter activity," which I have used temporarily, has a "ferrichrome import into cell" parent, which is a true path violation.

• I can propose a solution when I know if we should model uptake in the MF or not.
• One suggestion to simplify is to make the terms agnostic for the specific siderophore and use inputs and outputs to capture these.
• We should definitely always specify in the term label whether the siderophore is iron chelated, or not.

[ValWood]

More complete view:

It is not completely clear which terms refer to the export of the siderophore and which terms refer to import of the iron-siderophore, although there has clearly been some attempt to disambiguate these:

One of the main problems is the term

GO:1901678 iron coordination entity transport
(most of the children are for iron+chelate, and therefore are clearly describing the import)

GO:0015886    heme transport | is_a
GO:1902497    iron-sulfur cluster transmembrane transport | is_a
GO:0033214    siderophore-dependent iron import into cell | is_a
GO:0015891    siderophore transport

ALL except siderophore transport refer to the import systems
Suggest

• i) remove child
  GO:0015891    siderophore transport which should remove most of the exporters (which are children of GO:0015891    siderophore transport term)

• Once this change is through:
  check if there are any siderophore exporters remaining in this list

• a better name? Maybe iron-iron coordination entity transport?

GO:0015891 siderophore transport
is defined
The directed movement of siderophores, low molecular weight Fe(III)-chelating substances, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.

From the definition and children
It seems to be intended for just transport of the siderophores (siderophores are made and exported, to be used in import systems)

I'm assuming this from the children
GO:0044718    siderophore transmembrane transport | is_a
GO:0042935    achromobactin transport | is_a
GO:0042932    chrysobactin transport | is_a
GO:0042930    enterobactin transport

which are a separate set of terms to

GO:0033214 siderophore-dependent iron import into cell

So to realign this term with its intended meaning i.e.

• 2.0 remove parent GO:0033214 siderophore-dependent iron import into cell

• 2.1 some synonyms are incorrect and need removing
  iron-siderophore transport | exact [INCORRECT]
  siderochrome transport | narrow
  iron-siderochrome transport | narrow [INCORRECT]
  siderophore-iron transport | exact [INCORRECT]

• 2.3 After this we could probably make this term clearer by renaming it to
  "siderophore export across plasma membrane"
  but would need to review the terms to check it describes only siderophore exporters
  (I believe these are all ATPases, and that non-iron coordinated siderophores are only transported in this context)

3. We need to decide where to put the transporter specificity. It seems a bit overkill to represent every siderophore that is exported as a separate process term. Should we have a generic siderophore export process and separate terms for MF for specific exporters?

• 4. Add parent
  iron chelate transmembrane transporter activity to
  siderophore-iron transmembrane transporter activity

• 5. siderophore transmembrane transport
  This has similar issues to GO:0015891 siderophore transport
  but since it has only 8 direct annotations I'll rehouse the children (molecular functions), to the correct parents, then obsolete with reannotation suggestions for the direct annotations (some are "siderophore export across plasma membrane" , and some are GO:0033214 siderophore-dependent iron import into cell

(to begin the cleanup I removed the logical def/design pattern from siderophore transmembrane transport
which will get rid of the MF children)

[pgaudet]

Hi Val,

Thanks for looking into this. I had looked before but I know it was not complete.

1.i remove parent GO:0015891 siderophore transport

Do you mean you want to remove GO:0015891 siderophore transport as a child of iron coordination entity transport ? ?

It seems a bit overkill to represent every siderophore that is exported as a separate process term.

This is what I also thought, but there seem to be transporters specific for the export of the 'naked' siderophore, in orer to re-uptake later. If this term is not avilable anymore, how do you recommend we annotate these transporters?

I'd like to get rid of all 'transport' terms that dont mention. mechanism - either 'transmembrane' or endo/exocytosis. So the I think siderophore transport can be obsoleted and replaced by the TM version?

[ValWood]

Do you mean you want to remove GO:0015891 siderophore transport as a child of iron coordination entity transport ? ?

yes

This is what I also thought, but there seem to be transporters specific for the export of the 'naked' siderophore, in orer to re-uptake later. If this term is not avilable anymore, how do you recommend we annotate these transporters?

I think maybe we should keep the individual transporters (or create them)
in replacement of

GO:0015687 ferric-hydroxamate import into cell
would be
ferric-hydroxamate importer (or transporter?) activity part of GO:0033214 siderophore-dependent iron import into cell
but this is more a long-term suggestion once reorganized

the 'naked' siderophores won't have 'ferric' in the term name

I'd like to get rid of all 'transport' terms that dont mention. mechanism - either 'transmembrane' or endo/exocytosis. So the I think siderophore transport can be obsoleted and replaced by the TM version?

Agreed but I'd like to keep and rename siderophore transport and obsolete the TM version. They have been used identically but the TM version has fewer annotations.

but siderophore transport would be renamed to "siderophore export across plasma membrane"
(this is the only documented export mechanism)

[ValWood]

basket

basket (1).txt

[ValWood]

It is worth noting that iron-siderophore import can also apparently be by endocytosis (Partiularly in pathogens?) , although I have not =seen any annotated examples.
Export of the siderophore appeared to be only via TM transport.

[pgaudet]

Yes - that was another complication with these terms.

[pgaudet]

would be
ferric-hydroxamate importer (or transporter?)

This is a broader transport question. Right now we mostly dont have directionality in the MF branch. This needs to be applied consistently, whatever we do.

I had started to move all directionality into BP, but that is not yet complete. There are still 'influx' and 'efflux' transporters.

[ValWood]

I think in this instance it would be OK though

ferric-hydroxamate importer (or transporter?) activity part of GO:0033214 siderophore-dependent iron import into cell

it would be
ferric-hydroxamate transporter activity
part of GO:0033214 siderophore-dependent iron import into cell

I could not remember if the direction belonged on MF or BP