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

T hE secretory pathway of eukaryotic cells consists of a series of membrane-bound organelles. The correct sorting of proteins is essential to maintain complex structure and function of these organelles and requires a specific localization signal in each protein. To date, a few examples of such signals have been identified for ER proteins. One is the COOH-terminal Lys-Asp-Glu-Leu (KDEL, mammals) or His-Asp-Glu-Leu (HDEL, yeast) sequence (Munro and Pelham, 1987; Pelham et al., 1988) . The cis-Golgi receptor for this K(H)DEL sequence, Erd2p, has also been identified (Semenza et al., 1990; Lewis and Pelham, 1990) . Other signals are the COOH-terminal dilysine motif of type I transmembrane proteins (Jackson et al., 1990 ) and the NH:-terminal diarginine motif of type II transmembrane proteins (Schutze et al., 1994) . It is believed that the ER proteins harboring the K(H)DEL or dilysine motifs are retrieved from the early Golgi to the ER (Pelham, 1988; Dean and Pelham, 1990; Hsu et al., 1991; Lewis and Pelham, 1992; Jackson et al., 1993) .