Association between the 15-kDa selenoprotein and UDP-glucose : glycoprotein glucosyltransferase in the endoplasmic reticulum of mammalian cells

Mammalian selenocysteine-containing proteins characterized with respect to function are involved in redox processes and exhibit distinct expression pa tterns and cellular locations. A recently identified 15-kDa selenoprotein ( Sep15) has no homology to previously characterized proteins, and its functi on is not known. Here we report the intracellular localization and identifi cation of a binding partner for this selenoprotein which implicate Sep15 in the regulation of protein folding. The native Sep15 isolated from rat pros tate and mouse liver occurred in a complex with a 150-kDa protein. The latt er protein was identified as UDP-glucose:glycoprotein glucosyltransferase ( UGTR), the endoplasmic reticulum (ER)-resident protein, which was previousl y shown to be involved in the quality control of protein folding. UGTR func tions by glucosylating misfolded proteins, retaining them in the ER until t hey are correctly folded or transferring them to degradation pathways. To d etermine the intracellular localization of Sep15, we expressed a green fluo rescent protein-Sep15 fusion protein in CV-1 cells, and this protein was lo calized to the ER and possibly other perinuclear compartments. We determine d that Sep15 contained the N-terminal signal peptide that was essential for translocation and that it was cleaved in the mature protein. However, C-te rminal sequences of Sep15 were not involved in trafficking and retention of Sep15. The data suggest that the association between Sep15 and UGTR is res ponsible for maintaining the selenoprotein in the ER This report provides t he first example of the ER-resident selenoprotein and suggests a possible r ole of the trace element selenium in the quality control of protein folding .