Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain

It is also possible that Rerlp is a component of the general machinery that functions in the sorting of proteins in the cis-Golgi. It could help concentrate the ER-resident proteins to be retrieved or might block their forwarding to the later compartments. If the role of Rerlp is in fact general for multiple signals, its mutant should show pleiotropic effects on a variety of cargos. The small amount of missecreted BiP seen in the Arerl cells (Sato et al., 1995) could reflect such a general defect. On the other hand, missorting of the dilysine signal was not observed in the same ceils . Apparently, understanding of the structure and function of such general machinery requires further identification of components by genetic and biochemical studies. The RER2 gene we identified previously (Nishikawa and Nakano, 1993) appears to encode a hydrophilic protein which is peripherally associated with the ER membrane (M. Sato, S. Nishikawa, K. Sato, and A. Nakano, unpublished) . Its role could be implicated in the retention rather than in retrieval.