Glycobiology Advance Access originally published online on November 10, 2004
Glycobiology 2005 15(4):421-436; doi:10.1093/glycob/cwi014
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Glycobiology vol. 15 no. 4 © Oxford University Press 2004; all rights reserved.
Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins
2 Department of Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602-4712, and 3 Departments of Pathology and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030–3498
1 To whom correspondence should be addressed; e-mail: moremen{at}uga.edu
Received on October 27, 2004; accepted on November 5, 2004
In the endoplasmic reticulum (ER), misfolded proteins are retrotranslocated to the cytosol and degraded by the proteasome in a process known as ER-associated degradation (ERAD). Early in this pathway, a proposed lumenal ER lectin, EDEM, recognizes misfolded glycoproteins in the ER, disengages the nascent molecules from the folding pathway, and facilitates their targeting for disposal. In humans there are a total of three EDEM homologs. The amino acid sequences of these proteins are different from other lectins but are closely related to the Class I mannosidases (family 47 glycosidases). In this study, we characterize one of the EDEM homologs from Homo sapiens, which we have termed EDEM2 (C20orf31). Using recombinantly generated EDEM2, no 
-1,2 mannosidase activity was observed. In HEK293 cells, recombinant EDEM2 is localized to the ER where it can associate with misfolded 1-antitrypsin. Overexpression of EDEM2 accelerates the degradation of misfolded 1-antitrypsin, indicating that the protein is involved in ERAD.
Key words: EDEM / EDEM2 / ERAD / ER quality control / mannosidase
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