Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins.
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Recombinant EDEM2 showed no alpha-1,2-mannosidase activity, localized to the ER, associated with misfolded alpha-1-antitrypsin, and its overexpression accelerated ERAD of misfolded alpha-1-antitrypsin.
The role of EDEM2 compared with EDEM1 in ricin transport from the endoplasmic reticulum to the cytosol.
EDEM2 initiates mammalian glycoprotein ERAD by catalyzing the first mannose trimming step.
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Endogenous EDEM2 catalyzes the first mannose-trimming step Man9 to Man8B; EDEM2 is a novel-type Htm1 homologue, resolving the controversy over its catalytic activity.
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The catalytically inactivating E117Q mutant failed to restore gpERAD of ATF6alpha in EDEM2-KO cells, tying EDEM2's mannosidase activity to ERAD; SEL1L binds EDEM1 and EDEM3 but not EDEM2.
EDEM2 stably disulfide-bonded to TXNDC11 catalyzes the first mannose trimming step in mammalian glycoprotein ERAD.
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EDEM2 is stably disulfide-bonded to the thioredoxin-domain protein TXNDC11 (EDEM2 Cys558 to TXNDC11 Cys692 in the Trx5 CXXC motif); this covalent bond is essential for mannose trimming and gpERAD, and the purified EDEM2-TXNDC11 complex converts Man9GlcNAc2 to Man8GlcNAc2 isomer B in vitro - the first clear demonstration of in vitro mannosidase activity for an EDEM-family protein.
Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.
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Immunoprecipitated EDEM2 has bona fide alpha-mannosidase activity that is modest on free glycans and native glycoproteins but markedly higher on denatured/unfolded glycoproteins, providing a mechanism for preferential trimming of misfolded ERAD clients; oxidoreductases including TXNDC11 and PDI associate with EDEM2.
UGGT1-mediated reglucosylation of N-glycan competes with ER-associated degradation of unstable and misfolded glycoproteins.
MAN1B1 hydrolyses 1,2-linked mannose (a branch)
ER Quality Control Compartment (ERQC)
MAN1B1 hydrolyses a second 1,2-linked mannose (a branch)
MAN1B1 hydrolyses 1,2-linked mannose (c branch)
MAN1B1,EDEM2 hydrolyse 1,2-linked mannose (b branch)
Maturation of spike protein
N-glycan mannose trimming of Spike
UniProt entry Q9BV94 (EDEM2_HUMAN), ER degradation-enhancing alpha-mannosidase-like protein 2