Htm1p, a mannosidase-like protein, is involved in glycoprotein degradationin yeast

Misfolded proteins are recognized in the endoplasmic reticulum (ER), transp orted back to the cytoplasm and degraded by the proteasome. Processing inte rmediates of N-linked oligosaccharides on incompletely folded glycoproteins have an important role in their folding/refolding, and also in their targe ting to proteolytic degradation. In Saccharomyces cerevisiae, we have ident ified a gene coding for a non-essential protein that is homologous to manno sidase I (HTM1) and that is required for degradation of glycoproteins. Dele tion of the HTM1 gene does not affect oligosaccharide trimming. However, de letion of HTM1 does reduce the rate of degradation of the mutant glycoprote ins such as carboxypeptidase Y, ABC-transporter Pdr5-26p and oligosaccharyl transferase subunit Stt3-7p, but not of mutant Sec61-2p, a non-glycoprotein . Our results indicate that although Htm1p is not involved in processing of N-linked oligosaccharides, it is required for their proteolytic degradatio n. We propose that this mannosidase homolog is a lectin that recognizes Man (8)GlcNAc(2) oligosaccharides that serve as signals in the degradation path way.