RAS2 protein of Saccharomyces cerevisiae is methyl-esterified at its carboxyl terminus.

Yeast and mammalian RAS gene products are GTP-binding proteins that are posttranslationally localized to the inner surface of the plasma membrane. This localization is accomplished by the addition of a lipid moiety to a conserved cysteine residue close to the carboxyl terminus. In a previous report we showed that the mammalia Ha-ras protein is also modified posttranslationally by methyl esterification. Here we show that the yeast RAS2 protein is posttranslationally modified by methyl esterification at or near the carboxyl terminus. We also present evidence indicating that the methyl ester is linked to the conserved cysteine residue, implying that RAS2 protein is cleaved to expose this cysteine as the carboxyl-terminal residue. This maturation pathway may be shared by a family of proteins that are initially synthesized as soluble proteins and must become membrane-localized to function.