copper delivery

[ValWood]

the term for this is

GO:0015680 intracellular copper ion transport intracellular copper delivery | exact

but I don't think this is transport, it's just insertion?

see Cerqua C, Morbidoni V, Desbats MA, Doimo M, Frasson C, Sacconi S, Baldoin MC, Sartori G, Basso G, Salviati L, Trevisson E. | Related Articles

COX16 is required for assembly of cytochrome c oxidase in human cells and is involved in copper delivery to COX2. Biochim Biophys Acta. 2018 Jan 18;. [Epub ahead of print] PMID: 29355485

[krchristie]

@ValWood - this term is used for experimental annotations for several genes, some of which look like they match the definition, e.g. FET4, CTR2. Therefore, I think that this term needs to continue to be what it is.

Gene/product	Gene/product name	Annotation extension	Contributor Organism	Evidence
COX17	Copper metallochaperone that transfers copper to Sco1p and Cox11p	SGD	Saccharomyces cerevisiae S288C	IDA
COX17	Copper metallochaperone that transfers copper to Sco1p and Cox11p	SGD	Saccharomyces cerevisiae S288C	IMP
FET4	Low-affinity Fe(II) transporter of the plasma membrane	SGD	Saccharomyces cerevisiae S288C	IMP
CTR2	Low-affinity copper transporter of the vacuolar membrane	SGD	Saccharomyces cerevisiae S288C	IMP
Atox1	antioxidant 1 copper chaperone	RGD	Rattus norvegicus	IMP
CCS1	Copper chaperone for superoxide dismutase Sod1p	SGD	Saccharomyces cerevisiae S288C	IMP
CCS	Copper chaperone for superoxide dismutase	PINC	Homo sapiens TAS
COPT5	AT5G20650	TAIR	Arabidopsis thaliana	IMP

I took a quick look at the paper you mention, but it is not clear to me what COX16 is doing.

If you'd like to propose a new term specifically for 'copper delivery', please propose a new term with all the appropriate details:

name: [term name] namespace: BP def: "definition text "[definition dbxrefs, e.g. GOC:abc, PMID:12345678] is_a: [GO term] relationship: [any other appropriate relationships]

[ValWood]

The term already has the exact synonym "copper ion delivery" If this is not the case the term should be obsoleted because delivery and transport are separate functions.

Regardless of the "transmembrane transporter" annotations, this term needs to be addressed because it is not related in any way to the "copper ion transmembrane transport branch, so I think it was intended for the chaperones (it is not clear to me whether these are 'transporters'), but they are not transmembrane transporters.

It might be better for @pgaudet to handle this one because I now remember that this was one of the outstanding issues in the transmembrane transporter branch refactoring.

FET4 and CTR2 need to be moved to the "transmembrane transporter" branch.

[ValWood]

@pgaudet the position of copper iron import also needs to be addressed, it seems that this should be under "transmembrane transport" based on def and descendants.

[krchristie]

I'm fine with letting @pgaudet take care of this if she wants, but considering that longstanding GO practice is that the meaning of the term is defined by the definition, currently: Def: The directed movement of copper (Cu) ions within a cell.

I think that keeping this term with this existing meaning and removing the synonym, IF needed, would be more consistent with our stated practice.

[ValWood]

Yes but it's in the wrong place in the ontology in this case.....

[ValWood]

...in addition most of the usage is for the "chaperone", not the transmembrane transporter.

Probably obsoletion is the only way to deal with it in this case.

[pgaudet]

see also https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875331/

[pgaudet]

Hello,

Looking at these more closely, it seems like the odd balls in the annotations are FET4 and CTR2. Here's what I did:

1. Changed term label of 'GO:0015680 intracellular copper ion transport' to intracellular copper ion delivery
2. Changed parent to 'protein maturation' (as an aside: but is this really OK under 'gene expression'?)
3. Also changed definitions of the corresponding MF to "Directly binding to and delivering copper ions to a target protein." (also for the parent 'metallochaperone' and sibling 'iron chaperone'):
   • GO:0016530 metallochaperone activity
   • GO:0016531 copper chaperone activity
   • GO:0034986 iron chaperone activity

Another suggestion for the term label:

4. Under 'protein maturation there is 'protein maturation by iron-sulfur cluster transfer', so we could rename 'intracellular copper ion delivery' to 'protein maturation by copper ion transfer'?

If that works I will implement the changes and ask an annotation review for FET4 and CTR2.

Thanks, Pascale

[ValWood]

I agree with these proposed changes. @Antonialock could you glance over and see if this looks OK? (Antonia has been working on our iron-sulfur pathway and so should spot any problems with these).

Re the protein maturation under gene expression, the rationale is that: gene expression def: The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA or circRNA (for protein-coding genes) and the translation of that mRNA or circRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.

I think it is correct.

[Antonialock]

I'm not entirely sure

these cellular copper-related processes seem to exist

1. copper import into cell
2. protein maturation by copper ion transfer
3. homeostatic control (e.g. making sure that the cell gets rid of too much copper if needed - COMMD1? Also there is a high affinity importer that I guess is regulated somehow)
4. ?? intracellular trafficking of copper (eg ATP7B - binds cyosolic Cu and delivers to TGN. I don't know if 'delivery' = release, or if 'delivery' = incorporation into another protein? So this could be its own process or it could be part of 'protein maturation by copper ion transfer"

[pgaudet]

Hi @Antonialock,

This ticket is only about the copper chaperone ("intracellular copper ion delivery" - what I proposed to call "protein maturation by copper ion transfer"). I think that 2 and 4 are the same thing (or I dont know if they can really be distinguished): I think proteins carry copper in the intracellular environment and the copper can be transferred to specific target proteins

(I dont see how 'import into cell' and 'homeostatic control ' are related).

Thanks, Pascale

[pgaudet]

Looking at the ontology structure, I went ahead and renamed 'intracellular copper ion delivery' to ' protein maturation by copper ion transfer'

Pascale