MMS19 is not indirectly upstream of transcription, and isn't regulatory

[ValWood]

iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins

ERCC2/XPD is a target protein.

Challenge MF

receptor signaling complex adaptor activity

transcription coactivator activity (note that this paper PMID: 11279242 describes as "The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor." suggesting that hMMS19 may be an AF-1-specific transcriptional coactivator of estrogen receptor. (weasel words)

Challenge BP response to hormone DNA metabolic process DNA repair phosphorelay signal transduction system positive regulation of double-strand break repair via homologous recombination positive regulation of transcription, DNA-templated transcription, DNA-templated nucleotide-excision repair chromosome segregation

all seem to be indirect. iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins

To me it doesn't make sense to annotate to "regulation of transcription" when this is required for the integrity of the participating proteins.

This isn't regulatory.

Do you agree ?

@colinlog @RLovering @pgaudet

If so I will reises disputes. If not, can we add to tomorrows discussion?

[ValWood]

Ideally ERCC2/ would be added as a target protein, but I don't know how to describe the actual MF

[ValWood]

I disputed some of the indirect phenotypes in protein2GO

[sylvainpoux]

Hi @ValWood I removed some annotations but not all. MMS19 role in DNA repair is well documented and should not be deleted. Sylvain

[ValWood]

Doesn't MMS19 have a repair defect because which transfers critical FeS clusters to several key enzymes with functions in DNA repair and replication? https://pubmed.ncbi.nlm.nih.gov/27558664/ "A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance." Obviusly it is reqyired for replication, repain and genome integrity generally https://pubmed.ncbi.nlm.nih.gov/22678362/ https://pubmed.ncbi.nlm.nih.gov/22678361/ but it seems to be indirect?

As far as I know we don't normally annotate proteins required for the maturation of proteins involved in a process to that process.

@pgaudet thoughts?

[ValWood]

i.e this would have only a phenotype annotation

[sylvainpoux]

I see your point, I read the UniProt function. I think it is too preliminary to remove it. As most papers describe its role in DNA repair I would prefer to keep it for the moment.

[ValWood]

OK!