Gene Ontology annotation through association of InterPro records with GO terms

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:12610306

Role of EDEM in the release of misfolded glycoproteins from the calnexin cycle.

EDEM extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle; overexpression accelerates release and ERAD.

PMID:16449189

Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation.

Derlin-2 and -3 are associated with EDEM and p97 and provide the missing link between EDEM and p97 in degradation of misfolded glycoproteins.

PMID:19524542

EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex.

EDEM1 specifically binds non-native proteins in a glycan-independent manner; its mannosidase-like domain is required for SEL1L association but not for substrate binding.

PMID:19934218

A dual role for EDEM1 in the processing of rod opsin.

EDEM1 is a chaperone of rod opsin; it promotes degradation of misfolded P23H rod opsin and reduces aggregation, with binding independent of mannose trimming.

PMID:21062743

Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B and to late endoplasmic reticulum-associated degradation steps.

Mannose trimming enables handoff of a substrate glycoprotein from EDEM1 to the late ERAD lectin XTP3-B and downstream E3 ligases; EDEM1 binding itself is trimming-independent.

PMID:23233672

A shared endoplasmic reticulum-associated degradation pathway involving the EDEM1 protein for glycosylated and nonglycosylated proteins.

EDEM1 is used by both glycosylated and nonglycosylated misfolded substrates, binding nonglycosylated proteins through a region outside its mannosidase-like domain; ERAD machinery accumulates in the ERQC on proteasome inhibition.

PMID:24200403

The role of EDEM2 compared with EDEM1 in ricin transport from the endoplasmic reticulum to the cytosol.

EDEM1 (and EDEM2) promote retrotranslocation of the ricin A chain from the ER to the cytosol, modeling ERAD-substrate dislocation.

PMID:25092655

EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.

All endogenous EDEMs possess mannosidase activity; EDEM3 and to a lesser extent EDEM1 perform the second trimming step (Man8B to Man7), resolving the mannosidase-versus-lectin controversy.
EDEM1 has the weakest mannosidase activity of the three EDEMs and can also enhance gpERAD independently of catalysis (lectin-like) when overexpressed.

PMID:30374462

Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.

In vitro, EDEM1 (and EDEM2) mannosidase activity is modest on free oligosaccharides and native glycoproteins but significantly higher on a denatured glycoprotein, explaining how slow background trimming becomes selective for misfolded substrates; the EDEMs associate with oxidoreductases including PDI and TXNDC11.

PMID:32423001

EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired.

EDEM1 is found in auto-regulatory complexes with ERAD components; its N-terminal disordered region mediates interaction with misfolded proteins, and EDEM1 overexpression can drive client degradation via autophagy/ER-phagy when proteasomal degradation or dislocation is impaired.

PMID:38682256

Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.

EDEM1 is itself turned over by both ERAD (SEL1L/Hrd1, YOD1, XTP3B, ERdj3, VIMP, BAG6, JB12) and autophagy in folded-state-dependent manner; OS9 binds EDEM1 but did not drive its turnover. EDEM1 has a fast half-life (~3 h) and exists in soluble and membrane-associated forms.

PMID:38773321

ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction.

Pharmacologic or genetic inhibition of ERAD components, including silencing EDEM1, reroutes canonical ERAD clients (NHK, BACE457delta) to degradative endolysosomes via the ER-phagy receptor FAM134B and the LC3 lipidation machinery.

PMID:37528230

Mechanisms of substrate processing during ER-associated protein degradation.

Authoritative review placing EDEM-family mannosidases among the luminal processing factors that cooperate with chaperones and lectins to deliver misfolded glycoproteins to HRD1-SEL1L-dependent ERAD.

Reactome:R-HSA-1791155

Expression of EDEM

Reactome:R-HSA-6782685

EDEM1,3 hydrolyse (GlcNAc)2 (Man)8b to (GlcNAc)2 (Man)5

file:human/EDEM1/EDEM1-uniprot.txt

UniProt entry Q92611 (EDEM1_HUMAN), ER degradation-enhancing alpha-mannosidase-like protein 1

Single-pass type II ER membrane GH47 protein that extracts misfolded glycoproteins from the calnexin cycle and targets them for ERAD (N-glycan-independent, via SEL1L); has low mannosidase activity (Man8GlcNAc2 to Man7GlcNAc2); interacts with SEL1L, DERL2, DERL3.