The Saccharomyces cerevisiae MSI4 gene encodes the yeast counterpart of component A of Rab geranylgeranyltransferase.

We describe the isolation of MSI4 as a multicopy suppressor of ira1 (inhibitory regulator of Ras). We find it encodes a 66-kDa protein with three regions similar to component A of Rab geranylgeranyltransferase and Rab guanine nucleotide dissociation inhibitor. A gene disruption experiment showed that MSI4 is essential for cell growth. To investigate its functions further, we constructed a strain whose MSI4 is driven by the GAL1 promoter. This strain accumulated the endoplasmic reticulum precursor form of a vacuolar enzyme, carboxypeptidase Y, under the restrictive conditions. Moreover, we showed that the activity of geranylgeranyl-transferase for Ypt1p was very low in the mutant shifted to glucose medium. We propose that the MSI4 gene product is a yeast counterpart of component A of Rab geranylgeranyltransferase that is essential for Ypt1p to localize on membranes.