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

Stable Identifier
Reaction [uncertain]
Homo sapiens
Glycoproteins with major folding defects are sent to degradation by OS9:SEL1:SYVN1 dimer:DERL2
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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
Orthologous Events
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