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Target intelligence / Profile preview
ER degradation enhancing alpha-mannosidase like protein 3 (EDEM3)
- Target
- EDEM3
- Molecular classification
- Enzyme, Glycoside hydrolase family 47 (GH47), ER quality control factor, Lectin-like protein
01
Overview
ER degradation enhancing alpha-mannosidase like protein 3 is an ER-resident enzyme that accelerates the degradation of misfolded glycoproteins by trimming mannose residues on their N-glycans, tagging them for proteasomal destruction via the ER-associated degradation pathway. Loss or mutation of EDEM3 impairs glycoprotein quality control, resulting in accumulation of misfolded proteins and is associated with rare congenital disorders of glycosylation, developmental delay, and other systemic symptoms. EDEM3 may have both enzymatic and lectin-like properties, serving as a key quality control factor in protein homeostasis.
- Other names
- EDEM3Alpha-1,2-mannosidase EDEM3Endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 3
02
Mechanism of action
Drugs that inhibit mannosidase activity (e.g., kifunensine) block glycan trimming, stabilize misfolded proteins, and inhibit ER-associated degradation
03
Biological functions
ER-associated degradation (ERAD)Mannose trimming of misfolded glycoproteinsRecognition and targeting of misfolded glycoproteins for degradation
04
Disease associations
Congenital disorder of glycosylation (CDG-IIv; EDEM3-CDG)Non-specific syndromic intellectual disabilityOther protein misfolding disorders (inferred from its role in ERAD)
05
Safety considerations
Disruption of ERAD by modifying EDEM3 activity could lead to accumulation of misfolded proteins and cellular toxicityTherapeutic challenges include specificity and the risks of interfering in fundamental cell quality control mechanisms
06
Interacting drugs
No drugs directly targeting EDEM3 have been approved or are known at present; inhibitors like kifunensine (an alpha-mannosidase inhibitor used experimentally) affect ERAD pathways involving EDEM family members
07
Biomarkers
N-glycan profile analysis (used for diagnosis in EDEM3-CDG)Genetic testing for EDEM3 mutations (diagnostic for EDEM3-CDG)
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