Reactome | Ub-unfolded protein:(GlcNAc)2 (Man)9-5 translocates from ERQC to cytosol

Ub-unfolded protein:(GlcNAc)2 (Man)9-5 translocates from ERQC to cytosol

Stable Identifier

R-HSA-1022127

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane, endoplasmic reticulum quality control compartment

Synonyms

Glycoproteins with major folding defects are sent to degradation by OS9:SEL1:SYVN1 dimer:DERL2

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - N-glycan trimming in the ER and Calnexin/Calreticulin cycle (Homo sapiens)
      - Calnexin/calreticulin cycle (Homo sapiens)
        
        ER Quality Control Compartment (ERQC) (Homo sapiens)
        
        Ub-unfolded protein:(GlcNAc)2 (Man)9-5 translocates from ERQC to cytosol (Homo sapiens)

General

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Ub-unfolded protein:(GlcNAc)2 (Man)9-5 translocates from ERQC to cytosol

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Proteins with major folding defects are extracted from futile folding cycles in the calnexin chaperone system and the ER Quality Control Compartment, and are translocated back to the cytosol for ER-associated degradation (ERAD). The N-glycan is used as a signal to distinguish proteins to be degraded, by direct binding to a ubiquitin ligase complex composed of, minimally, an E3 ubiquitin-protein ligase, protein sel-1 homolog 1 (SEL1L), derlin-2 (DERL2) and protein OS-9 (OS9) (Christianson et al. 2008, Bernasconi et al. 2008, Alcock & Swanton 2009; review Olzmann et al. 2013). The mechanism of translocation is unknown.

Literature References

PubMed ID	Title	Journal	Year
19084021	Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress and facilitates ubiquitination of misfolded glycoproteins Alcock, F, Swanton, E	J. Mol. Biol.	2009
23232094	The mammalian endoplasmic reticulum-associated degradation system Christianson, JC, Kopito, RR, Olzmann, JA	Cold Spring Harb Perspect Biol	2013
18264092	OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD Tyler, RE, Christianson, JC, Kopito, RR, Shaler, TA	Nat. Cell Biol.	2008
18417469	A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal Molinari, M, Luban, J, Pertel, T, Bernasconi, R	J. Biol. Chem.	2008