ArticleThe Journal of cell biology2014
EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.
Article in The Journal of cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 157 citations in OpenAlex.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Membralin Assembles a MAN1B1-VCP Complex to Target Foreign Glycoproteins from the Endoplasmic Reticulum to Lysosomes for Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modifiable risk factors and skin cancers: a multi-omics Mendelian randomization study from causal inference to drug target discovery.Frontiers in genetics · 2026Article
- Studying Glycan-Dependent ERAD of Misfolded Glycoproteins in Plants.Methods in molecular biology (Clifton, N.J.) · 2026Article
- TMEM131-Mediated Soluble TRAIL Triggered Type II Alveolar Epithelial Cell Senescence in Radiation-Induced Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- N-glycan-dependent protein maturation and quality control in the ER.Nature reviews. Molecular cell biology · 2025Review
- Initiation of ERAD by the bifunctional complex of Mnl1/Htm1 mannosidase and protein disulfide isomerase.Nature structural & molecular biology · 2025Article
- Glycosylation as an intricate post-translational modification process takes part in glycoproteins related immunity.Cell communication and signaling : CCS · 2025Review
- N-Glycosylation Modification of Fzd4 Is Essential for the Fzd4-Wnt-β-Catenin Signalling Axis.Journal of cellular and molecular medicine · 2025Article
- The endoplasmic reticulum degradation-enhancing α-mannosidase-like protein 3 attenuates the unfolded protein response and has pro-survival and pro-viral roles in hepatoma cells and hepatocellular carcinoma patients.Journal of biomedical science · 2025Article
- Quantitative DIA-based proteomics unveils ribosomal biogenesis pathways associated with increased final size in three-year-old Chinese mitten crab (Eriocheir sinensis).BMC genomics · 2025Article
- Development of an Endoplasmic Reticulum Stress-Related Diagnostic Signature in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- UGGT1-mediated reglucosylation ofeLife · 2024Article
- IGFBP6 Modulates Proteostasis by Activating ATF4 Targets and Reducing ER Retrotranslocon Expression.Doklady. Biochemistry and biophysics · 2024Article
- Initiation of ERAD by the bifunctional complex of Mnl1 mannosidase and protein disulfide isomerase.bioRxiv : the preprint server for biology · 2024Article
- Mutations in fibronectin dysregulate chondrogenesis in skeletal dysplasia.Cellular and molecular life sciences : CMLS · 2024Article
- Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation.Cell death & disease · 2024Article
- Analysis of Protein Glycosylation in the ER.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- EDEM1 regulates the insulin mRNA level by inhibiting the endoplasmic reticulum stress-induced IRE1/JNK/c-Jun pathway.iScience · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycoproteins misfolded in the endoplasmic reticulum (ER) are subjected to ER-associated glycoprotein degradation (gpERAD) in which Htm1-mediated mannose trimming from the oligosaccharide Man8GlcNAc2 to Man7GlcNAc2 is the rate-limiting step in yeast. In contrast, the roles of the three Htm1 homologues (EDEM1/2/3) in mammalian gpERAD have remained elusive, with a key controversy being whether EDEMs function as mannosidases or as lectins. We therefore conducted transcription activator-like effector nuclease-mediated gene knockout analysis in human cell line and found that all endogenous EDEMs possess mannosidase activity. Mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1. Most surprisingly, the upstream mannose trimming from Man9GlcNAc2 to Man8GlcNAc2 is conducted mainly by EDEM2, which was previously considered to lack enzymatic activity. Based on the presence of two rate-limiting steps in mammalian gpERAD, we propose that mammalian cells double check gpERAD substrates before destruction by evolving EDEM2, a novel-type Htm1 homologue that catalyzes the first mannose trimming step from Man9GlcNAc2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.