Human EDEM2, a novel homolog of family 47 glycosidases, is involved in ER-associated degradation of glycoproteins

Glycobiology. 2005 Apr;15(4):421-36. doi: 10.1093/glycob/cwi014. Epub 2004 Nov 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Line
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum / genetics
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Protein Folding*
  • alpha 1-Antitrypsin / metabolism*
  • alpha-Mannosidase / genetics
  • alpha-Mannosidase / metabolism*


  • Glycoproteins
  • alpha 1-Antitrypsin
  • EDEM2 protein, human
  • alpha-Mannosidase