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Source ontology files for the Gene Ontology
http://geneontology.org/page/download-ontology
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ERAD question #20914

Open ValWood opened 3 years ago

ValWood commented 3 years ago

These terms seem to be all describing the same process?

pgaudet commented 3 years ago

Who can answer this ? Most EXP annotations are from SGD @srengel do you agree to merge those terms?

ValWood commented 3 years ago

Actually it might not be so simple. In this historical (open) ticket, https://github.com/geneontology/go-ontology/issues/14384 there is a bit more information. I forgot about this. I think quite a few of the definitions are not quite right. At present they all sound the same.

ValWood commented 3 years ago

Also, look at this even older ticket: https://github.com/geneontology/go-ontology/issues/13717

srengel commented 3 years ago

not totally clear what to do here, and reading those 2 older tickets make me even less sure. it's confusing that glycoprotein folding terms are being requested, because those should like instances to me. is glycoprotein folding QC really that different from other protein folding QC?

ValWood commented 3 years ago

@srengel you are correct. The ERAD part is the same. However there is a pathway for glycoproteins which proceeds ERAD. glycoproteins see https://ars.els-cdn.com/content/image/1-s2.0-S0014579315006468-gr2_lrg.jpg

Here are some actions we can do immediately.

ERAD pathway (GO:0036503) The protein catabolic pathway which targets endoplasmic reticulum (ER)-resident proteins for degradation by the cytoplasmic proteasome. It begins with recognition of the ER-resident protein, includes retrotranslocation (dislocation) of the protein from the ER to the cytosol, protein modifications necessary for correct substrate transfer (e.g. ubiquitination), transport of the protein to the proteasome, and ends with degradation of the protein by the cytoplasmic proteasome. [PMID:20940304, PMID:21969857]

into ERAD pathway (GO:0036503) these seem to be identical?

into ERAD pathway (GO:0036503) these seem to be identical? (all ERAD is Ubiquitin/proteasome mediated as far as we know?)

Definition | Parents An ERAD pathway whereby endoplasmic reticulum (ER)-resident glycoproteins are targeted for degradation. Includes differential processing of the glycoprotein sugar chains, retrotranslocation to the cytosol and degradation by the ubiquitin-proteasome pathway. A glycoprotein is a compound in which a carbohydrate component is covalently bound to a protein component.

merge into ERAD pathway (GO:0036503)

    • [ ] Add a new term GO:NEW endoplasmic reticulum quality control Any of the protein or glycoprotein quality control and degradation pathways. child of GO:0006515 protein quality control for misfolded or incompletely synthesized proteins

as a parent of GO:0036503 ERAD pathway GO:0061857 endoplasmic reticulum stress-induced pre-emptive quality control

    • [ ] GO:0006515 protein quality control for misfolded or incompletely synthesized proteins def is too narrow The chemical reactions and pathways resulting in the breakdown of misfolded or attenuated proteins. Should also include "refolding" the breakdown only occurs if proteins are terminally misfolded. There are other components to QC.
    • [ ] Add a new term https://github.com/geneontology/go-ontology/issues/14384 see background here: "endoplasmic reticulum quality control of glycoprotein folding" The endoplasmic reticulum quality control process that ensures that only corrected folded proteins stay in the ER and contin ue to the secretory pathway. This process involves a number of genes including calnexin, UGGT, glucosidase and glucosidase II, among others. Terminally misfolded proteins proceed to the ERAD pathway. ref D'Alessio et al 2010 Semin Cell Dev Biol. 21, 491-9) .

is_a GO:NEW endoplasmic reticulum quality control Note from the expert: The ERAD pathway (Endoplasmic reticulum glycoprotein associated degradation) is a process that occurs when the previous (QC) mechanism has failed: irreversibly misfolded glycoproteins are retrotranslocated to the cytosol and degraded in proteasomes.

more to follow.....I just need to check the other tickets....

ValWood commented 3 years ago
    • [ ] GO:0006515 protein quality control for misfolded or incompletely synthesized proteins parentage is incorrect. Protein quality control includes more than proteolysis/catabolism.

It will and up as quite a 'high level' term.

    • [ ] merge GO:0051603 proteolysis involved in cellular protein catabolic process into GO:0044257 cellular protein catabolic process
    • [ ] GO:0006508 proteolysis is a MF? obsolete?
ValWood commented 3 years ago

Finally....

    • [ ]

GO:0030968 endoplasmic reticulum unfolded protein response Definition (GO:0030968 GONUTS page) The series of molecular signals generated as a consequence of the presence of unfolded proteins in the endoplasmic reticulum (ER) or other ER-related stress; results in changes in the regulation of transcription and translation. PMID:12042763

and his term in a different part of the ontology GO:0006983 ER overload response The series of molecular signals generated by the accumulation of normal or misfolded proteins in the endoplasmic reticulum and leading to activation of transcription by NF-kappaB. PMID:10390516

seem to be describing the same process.

srengel commented 3 years ago

just ran across this paper that defines a new EGAD pathway (Endosome and Golgi-Associated Degradation) that selectively extracts membrane proteins at Golgi and endosomes for degradation by cytosolic proteasomes. https://pubmed.ncbi.nlm.nih.gov/31368600/

posting here because anyone reading this ticket might also be interested in this EGAD? any problems with me requesting this new term? "EGAD pathway" = "The protein catabolic pathway which selectively extracts ER-resident membrane proteins exported to the Golgi and endosomes for degradation by cytosolic proteasomes. It begins with phosphorylation of the ER-resident membrane protein, which triggers export of the protein from the ER to the Golgi and endosomes, followed by polyubiquitination by the Dsc E3 ubiquitin ligase complex and extraction of the ubiquitinated target, and ends with proteasomal degradation."