{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cormier JH"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["627-33"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2740909"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["34(5)"],"pubmed_abstract":["Terminally misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently cleared by the ER-associated degradation (ERAD) pathway. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however, the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined. EDEM1 (ER degradation-enhancing alpha-mannosidase-like 1 protein) has been proposed to play a role in ERAD substrate signaling or recognition. We show that EDEM1 specifically binds nonnative proteins in a glycan-independent manner. Inhibition of mannosidase activity with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDEM1 substrate binding but diminished its association with the ER membrane adaptor protein SEL1L. These results support a model whereby EDEM1 binds nonnative proteins and uses its mannosidase-like domain to target aberrant proteins to the ER membrane dislocation and ubiquitination complex containing SEL1L."],"journal":["Molecular cell"],"pubmed_title":["EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex."],"pmcid":["PMC2740909"],"funding_grant_id":["CA79864","R01 CA079864","R01 CA079864-10","T32 GM008515"],"pubmed_authors":["Hebert DN","Cormier JH","Tamura T","Sunryd JC"],"additional_accession":[]},"is_claimable":false,"name":"EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.","description":"Terminally misfolded or unassembled secretory proteins are retained in the endoplasmic reticulum (ER) and subsequently cleared by the ER-associated degradation (ERAD) pathway. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however, the mechanisms of substrate recognition and sorting to the ERAD pathway are poorly defined. EDEM1 (ER degradation-enhancing alpha-mannosidase-like 1 protein) has been proposed to play a role in ERAD substrate signaling or recognition. We show that EDEM1 specifically binds nonnative proteins in a glycan-independent manner. Inhibition of mannosidase activity with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDEM1 substrate binding but diminished its association with the ER membrane adaptor protein SEL1L. These results support a model whereby EDEM1 binds nonnative proteins and uses its mannosidase-like domain to target aberrant proteins to the ER membrane dislocation and ubiquitination complex containing SEL1L.","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Jun","modification":"2025-04-22T02:08:08.059Z","creation":"2019-03-27T00:24:50Z"},"accession":"S-EPMC2740909","cross_references":{"pubmed":["19524542"],"doi":["10.1016/j.molcel.2009.05.018"]}}