NTR: inner nuclear membrane associated protein degradation pathway (INMAD)

[ValWood]

Please provide as much information as you can:

• Suggested term label: inner nuclear membrane-associated protein degradation pathway or INMAD pathway (this is the nuclear inner membrane pathway analogous to ERAD for the ER and we have GO:0036503 ERAD pathway

• Definition (free text)

A protein quality control pathway that removes ubiquitinated proteins from the nuclear inner membrane before transferring them to the proteasome for degradation

• Reference, in format PMID:####### https://www.pombase.org/reference/PMID:37694715

• Gene product name and ID to be annotated to this term

doa10 (ligase), ubc6, ubc7, cdc48

• Parent term(s)

I would put it under "nuclear protein quality control by the ubiquitin-proteasome system (GO:0071630)" The chemical reactions and pathways resulting in the breakdown of misfolded proteins via a mechanism in which the proteins are transported to the nucleus for ubiquitination, and then targeted to proteasomes for degradation. PMID:20080635 PMID:21211726 PMID:21324894

But is this definition correct? I assumed it was for nuclear resident proteins. Why are proteins transported to the nucleus for degradation, this definition smells funny....(I will check the definition refs shortly)

But this appears to be for resident nuclear proteins . INMAD is for proteins that need to be extracted from the INM (analogous to ERAD)

• Children terms (if applicable) Should any existing terms that should be moved underneath this new proposed term?

• Synonyms (please specify, EXACT, BROAD, NARROW or RELATED)

INM-associated degradation EXACT INMAD pathway (depending on term name used)

• Cross-references

• For enzymes, please provide RHEA and/or EC numbers.

• Can also provide MetaCyc, KEGG, Wikipedia, and other links.

• Any other information

[ValWood]

I don't think we can use https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824284/ to support the degradation of non nuclear resident substrates because it is using an artificial construct for the assay.

The second reference says In yeast, the nuclear-localized ubiquitin ligase San1 specifically ubiquitinates abnormal nuclear proteins for proteasome degradation (Gardner et al., 2005)

The third reference https://pubmed.ncbi.nlm.nih.gov/21324894/ talks about nuclear substrates. I'll open a new ticket to revise the defintion

[ValWood]

With this definition change https://github.com/geneontology/go-ontology/issues/26433 the proposed parent will be appropriate

[ValWood]

[Term] id: GO:0180027 name: inner nuclear membrane-associated protein degradation pathway namespace: biological_process def: "A protein quality control pathway that removes ubiquitinated proteins from the nuclear inner membrane before transferring them to the proteasome for degradation." [PMID:37694715] synonym: "INMAD pathway" EXACT [] is_a: GO:0071630 ! nuclear protein quality control by the ubiquitin-proteasome system property_value: term_tracker_item "https://github.com/geneontology/go-ontology/issues/26432" xsd:anyURI created_by: vw creation_date: 2023-11-20T10:07:35Z