THE SACCHAROMYCES-CEREVISIAE-SCS2 GENE-PRODUCT, A HOMOLOG OF A SYNAPTOBREVIN-ASSOCIATED PROTEIN, IS AN INTEGRAL MEMBRANE-PROTEIN OF THE ENDOPLASMIC-RETICULUM AND IS REQUIRED FOR INOSITOL METABOLISM

The Saccharomyces cerevisiae SCS2 gene has been cloned as a suppressor of inositol auxotrophy of CSE1 and hac1/ire15 mutants (J. Nikawa, A. Murakami, E. Esumi, and K. Hosaka, J. Biochem. 118:39-45, 1995) and ha s homology with a synaptobrevin/VAMP-associated protein, VAP-33, clone d from Aplysia californica (P. A. Skehel, K. C. Martin, E. R. Kandel, and D. Bartsch, Science 269:1580-1583, 1995). In this study we have ch aracterized an SCS2 gene product (Scs2p). The product has a molecular mass of 35 kDa and is C-terminally anchored to the endoplasmic reticul um, with the bulk of the protein located in the cytosol. The disruptio n of the SCS2 gene causes yeast cells to exhibit inositol auxotrophy a t temperatures of above 34 degrees C, Genetic studies reveal that the overexpression of the INO1 gene rescues the inositol auxotrophy of the SCS2 disruption strain. The significant primary structural feature of Scs2p is that the protein contains the 16-amino-acid sequence conserv ed in yeast and mammalian cells. The sequence is required for normal S cs2p function, because a mutant Scs2p that lacks the sequence does not complement the inositol auxotrophy of the SCS2 disruption strain. The refore, the Scs2p function might be conserved among eukaryotic cells.