Saccharomyces TIM10, TIM12 gene function annotations

[LiNiMGI]

Hi Stacia @srengel
I am working on a project of “human genes no IBA MF’ to see whether there is data that can be used to PAINT the gene tree.
And I noticed:
TIM10, yeast annotated to protein transporter activity IDA/IMP,
TIM12 yeast annotated to protein transmembrane transporter activity IDA/IMP
While human annotated the ortholog TIMM10 to membrane insertase activity IDA

Do you think ‘membrane insertase activity GO:0032977” better describes the yeast TIM10 and TIM12 function here?
Thanks,
Li

[hattrill]

I think this one is a bit tricky: the definition GO:0042719 mitochondrial intermembrane space protein transporter complex is:
Soluble complex of the mitochondrial intermembrane space composed of various combinations of small Tim proteins; acts as a protein transporter to guide proteins to the Tim22 complex for insertion into the mitochondrial inner membrane.
So that seems ok

In these protein transporters, chaperones are involved in the process of transport - they kind of pull the subunits through the transport machinery and they are not protein folding chaperones. contribute_to ;-) ?

[ValWood]

ok so all GO:0042719 mitochondrial intermembrane space protein transporter complex subunits get

‘membrane insertase activity GO:0032977” contributes_to
?

[hattrill]

Or may be just 'protein carrier chaperone'?
Editting this as looking at GO:0140318 protein transporter activity "Directly binding to a specific protein and delivering it to a specific cellular location. PMID:18706423 " is actually perfect and the example given in the comment say "Examples of protein carriers include the soluble TIM chaperone complexes of S. cerevisiae Tim9-Tim10 and Tim8-Tim13, that provide a shuttle system between TOM and the membrane insertases TIM22 and SAM and, thus, ensure that precursors are kept in a translocation-competent conformation."

[hattrill]

and Timm22 is the insertase?

[ValWood]

OK that makes more sense. That's what I thought originally!

However:

TIM22 mitochondrial import inner membrane insertion complex (GO:0042721)
A multi-subunit complex embedded in the mitochondrial inner membrane that mediates the inner membrane insertion of multi-transmembrane spanning proteins that contain internal targeting elements. In yeast cells, TIM22 is a 300-kDa complex, consisting of four membrane integral subunits, Tim22, Tim54, Tim18 and Sdh3, and a peripheral chaperone complex consisting of the small TIM proteins, Tim9-Tim10-Tim12. [PMID:27554484, PMID:12191765]

So
Tim22 membrane insertase activity (GO:0032977) (contributes_to)
Tim54 membrane insertase activity (GO:0032977) (contributes_to)
Tim18 GO:0043495 protein-membrane adaptor activity
Sdh23 GO:0043495 protein-membrane adaptor activity (note this is also adaptor for Succinate DH complex)

Tim9 protein carrier chaperone (GO:0140597)
Tim10 protein carrier chaperone (GO:0140597)

?

The one thing I find odd about this is that
"protein carrier chaperone" is a parent of "membrane insertase activity", but these are different activities molecularly

[hattrill]

Yes, I can kind of see why insertases are a classes as protein carrier chaperone - mechanisically, they are quite strange - they mediate the partition of the hydrophobic portion of the TM protein into the bilayer by providing hydrophobic interaction interfaces. However, it becomes blurred with TM transport as a TIM23 variant TIM23SORT acts as an insertase rather than a TM transporter...

For Tim9 and Tim10, GO:0140318 protein transporter activity is just as valid as protein carrier chaperone when comparing the MF defs. As they are intergral to transport, perhaps protein transporter activity is ok (just not TM transporter activity)

[ValWood]

Most publications depict and describe tim10/12 as actual chaperones:

https://www.sciencedirect.com/science/article/pii/S002228361200784X

They are in the intermembrane space and bind to the cargo. But I don't think it is correct to describe as transporters (even though they are involved in the transport process), because the movement is 'not directed' which is necessary to describe a a transporter.

That's why "protein carrier chaperone" isn't a transporter.

The thing I find odd is describing an integrate as a "protein carrier chaperone", but maybe that is OK?

[hattrill]

I also find the integrase odd as a chaperone - I think with both integrases and the tim9-10 there are arguments to have them as transporters and/or chaperones.

[srengel]

hi guys, what is the conclusion here? please advise.