tpv: cotranslational protein targeting to membrane

[gocentral]

cotranslational protein targeting to membrane
http:https://www.ebi.ac.uk/QuickGO/GTerm?id=GO:0006613#term=ancchart

ends up as "membrane organization" via
GO:0072657 protein localization to membrane

However, cotranslational protein targeting to membrane is not always 'membrane organization'
(for example if transported into the ER lumen)

Reported by: ValWood

Original Ticket: geneontology/ontology-requests/11747

[gocentral]

Maybe two different processes should be distinguished here - ones where the protein remains in the membrane ("targeting TO") and ones where the protein traverses the membrane ("targeting THROUGH"). The logic sounds OK; the amount of legacy cleanup work sounds horrible. Or change the definition to explicitly allow both "to" and "through" and re-do the parentage? And proteins destined to remain in the membrane get an additional annotation to "membrane organization"?

Original comment by: deustp01

[gocentral]

• labels: --> parent query
• assigned_to: Tanya Berardini

Original comment by: tberardini

[gocentral]

Reviewing this thread, I agree with Peter. The definition can be interpreted as 'THROUGH' even though the term name states 'TO the membrane.' (Def:The targeting of proteins to a membrane that occurs during translation. The transport of most secretory proteins, particularly those with more than 100 amino acids, into the endoplasmic reticulum lumen occurs in this manner, as does the import of some proteins into mitochondria. ) We need to clean this up.

My suggestion:

1. Add a comment to the cotranslational term to say that it means targeting 'to' NOT 'through' a membrane. "Annotations to gene products that take the protein THROUGH the membrane into an organelle should not use this term."
2. Modify second sentence of cotranslational definition from
   "The transport of most secretory proteins, particularly those with more than 100 amino acids, into the endoplasmic reticulum lumen occurs in this manner, as does the import of some proteins into mitochondria. "

to

"The transport of most secretory proteins, particularly those with more than 100 amino acids, into the endoplasmic reticulum lumen BEGINS in this manner, as does the import of some proteins into mitochondria."

Note that 'SRP-dependent cotranslational protein targeting to membrane' is transitively part of 'protein localization to ER'. This is consistent with the proposed text change.

I think these changes will address the problem.

Original comment by: tberardini

[tberardini]

Hi Val,
Do the changes proposed here help address your issues? It clarifies the THROUGH vs TO problem in the text definitions and does NOT change anything in the parentage. I'm still thinking about what to do with the parentage, splitting out the 'SRP-...." to be THROUGH somehow and unlinking that from THROUGH, so that there's no implied or direct link to 'membrane organization.'

[tberardini]

Right now, on a Friday afternoon, your solution sounds pretty good. I'll revisit on Monday. Would we then be updating all the other similarly named terms like this:

SRP-dependent cotranslational protein targeting to membrane
SRP-dependent cotranslational protein targeting to membrane, docking
SRP-dependent cotranslational protein targeting to membrane, signal sequence processing
SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
SRP-dependent cotranslational protein targeting to membrane, translocation

to

SRP-dependent cotranslational protein targeting to ER
SRP-dependent cotranslational protein targeting to ER, docking
SRP-dependent cotranslational protein targeting to ER, signal sequence processing
SRP-dependent cotranslational protein targeting to ER, signal sequence recognition
SRP-dependent cotranslational protein targeting to ER, translocation

[ValWood]

It might require some more thought...

Does targeting end when the SRP docks with the SRP receptor? (i.e recognition and docking)
Are processing and translocation 'post' targeting?

This might help if the SRP is also responsible for the decision to retain in the membrane or end up in the lumen. I haven't been able to find any info on specific cargo, but some images show both destinations.

There are other (SRP-independent) mechanisms to get into the ER and I'm unsure if cargo of different import mechanisms have different final destinations (i.e. ER lumen, OR integral, extrinsic, intrinsic or anchored to membrane.

This is the 'translocation' def...this seems to be 'post targeting'?
The process during cotranslational membrane targeting wherein proteins move across a membrane. SRP and its receptor initiate the transfer of the nascent chain across the endoplasmic reticulum (ER) membrane; they then dissociate from the chain, which is transferred to a set of transmembrane proteins, collectively called the translocon. Once the nascent chain translocon complex is assembled, the elongating chain passes directly from the large ribosomal subunit into the centers of the translocon, a protein-lined channel within the membrane. The growing chain is never exposed to the cytosol and does not fold until it reaches the ER lumen.

The SRP and its receptor have a role in 'initiating' this process but this could be considered independent of the targeting role (or maybe it would more correctly be enabled_by rather than a part_of role?)
This def also implies that the (at least initial) destination or all SRP cargo is the lumen....

[pgaudet]

see also See also #13758