title: Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins.
abstract: 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 alpha-1,2 mannosidase activity was observed. In HEK293 cells, recombinant EDEM2 is localized to the ER where it can associate with misfolded alpha1-antitrypsin. Overexpression of EDEM2 accelerates the degradation of misfolded alpha1-antitrypsin, indicating that the protein is involved in ERAD.
authors.affiliation: Department of Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA 30602-4712, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Mast
authors.forename: Krista
authors.initials: K
authors.lastname: Diekman
authors.forename: Khanita
authors.initials: K
authors.lastname: Karaveg
authors.forename: Ann
authors.initials: A
authors.lastname: Davis
authors.forename: Richard N
authors.initials: RN
authors.lastname: Sifers
authors.forename: Kelley W
authors.initials: KW
authors.lastname: Moremen
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017510:Protein Folding; D000515:alpha 1-Antitrypsin / Q000378:metabolism*; D043323:alpha-Mannosidase / Q000235:genetics / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D000515:alpha 1-Antitrypsin; C497155:EDEM2 protein, human; D043323:alpha-Mannosidase