#11680 NTR: retrotranslocation complex

[RFoulger]

New term requests for protein complexes involved in retrograde transport of proteins from the ER to the cytosol during ERAD (ER-associated protein degradation):

endoplasmic reticulum retrotranslocation complex ; GO:NEW1
A multi-protein endoplasmic reticulum complex that transports protein substrates from the endoplasmic reticulum to the cytosol for degradation by the cytosolic proteasome. In mammals, can contain at least Derlin-1, VCP-interacting membrane protein (VIMP), ER-specific ubiquitin protein ligases (E3 enzymes) and the ATPase p97/VCP.
exact synonym: dislocation complex [PMID:24807418]
narrow synonym: Derlin-1 dislocation complex [PMID:18555783, PMID:15215856]
narrow synonym: Derlin-1 complex [PMID:16186510]
broad synonym: retrotranslocation complex [PMID:23665563]
PMID:15215856
PMID:16186510
GOC:bf/GOC:PARL
is_a: protein complex GO:0043234
part_of: endoplasmic reticulum membrane ; GO:0005789
intersection_of: GO:0043234 ! protein complex
intersection_of: capable_of_part_of GO:0006289 ! retrograde protein transport, ER to cytosol ; GO:0030970

Derlin-1-VIMP complex ; GO:NEW2
A protein complex containing, in mammals, Derlin-1 and VCP-interacting membrane protein (VIMP). The complex links the p97/VCP-containing ATPase complex with Derlin-1 during translocation of protein substrates from the endoplasmic reticulum to the cytosol for degradation by the cytosolic proteasome.
part_of: retrotranslocation complex ; GO:NEW1
is_a: protein complex GO:0043234
exact synonym: Derlin-1/VIMP complex [PMID:15215856]
PMID:15215856
PMID:16186510
GOC:bf/GOC:PARL

NB: There's probably various retrotranslocation complexes that assemble along the way to facilitate the various steps of the retrograde transport, so I've kept the first term broad.

Any comments before I do the edits?
Thank you!

[David Hill]

Hi Becky,

Does the intersection of the first term really create a necessary and sufficient definition? Are there other complexes that take part in the process? If so, then maybe move those relations out of the cross-product def. Otherwise looks good.

-D

[RFoulger]

Hi David,

Originally I defined the retrotranslocation complex as containing everything that was necessary for the transported protein to move across the ER membrane into the cytosol. Typically this involves:
-Substrate recognition proteins
-Derlins or other candidate proteins that form a channel
-ER ubiquitin ligases that modify the protein at the cytosolic side after a portion of the substrate has emerged in the cytosol
-An ATPase complex that pulls the complex out of the membrane.

We have a term for the 'pulling' ATPase complex already: GO:0034098
And we have some ER ubiquitin ligase complex terms: GO:0000835 and children

Let me do a little more reading about the sequence of events in forming the ERAD machinery- it may be that smaller complexes (e.g. A Derlin-containing translocon) may be more useful rather than one large complex with HAS_PART links. In which case I'll change the intersection to be a capable_of_part_of relationship instead.

Thanks,
Rebecca

[David Hill]

OK. Makes sense.
-D

[RFoulger]

For now, created Derlin-1-VIMP complex ; GO:0036502

[RFoulger]

Coming back to this, I think it makes most sense to create a more defined term:

Derlin-1 retrotranslocation complex ; GO:NEW
Synonyms:
Derlin-1 complex [PMID;18555783] (exact)
Derlin-1 protein dislocation complex [PMID:18555783] (exact)
ERAD protein dislocation complex [PMID:18555783] (broad)
Derlin-1 retro-translocation complex [GOC:bf] (exact)
Derlin-1 retrotranslocon [GOC:bf] (exact)
Definition:
A protein complex that functions in the retrotranslocation step of ERAD (ER-associated protein degradation) and includes at its core, Derlin-1 oligomers forming a retrotranslcoation channel.
PMID: 15215856, PMID:16186510
Relationships:
part_of: endoplasmic reticulum membrane ; GO:0005789
is_a: protein complex ; GO:0043234
capable-of-part-of: retrograde protein transport, ER to cytosol ; GO:0030970
Comment:
The Derlin-1 retrotranslocation complex is likely to assemble in steps, thereby containing different components at different stages of the retrotranslocation process.

[RFoulger]

Added: Derlin-1 retrotranslocation complex ; GO:0036513