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 should also be mentioned here that the effect of the Secl2p TMD is not completely Rerlp-dependent. Even in the absence of Rerlp, a significant amount of DSD is localized to the ER. This might indicate that multiple pathways exist in the retrieval system. The fact that the disruption of the RER1 gene is not lethal could also suggest the redundancy of the retrieval mechanism. Perhaps the deletion of Rerlp only partially impairs the function of the retrieval machinery. Alternatively, the TMD of Sec12p may also harbor a weak signal for static retention. The observation that the rate of {xl---~6 mannosyl modification on DSD is not as fast as Dap2p supports this possibility. More extensive analysis on the amino acid residues in the TMD might separate such different effects in terms of Rerlp dependency.