MAMMALIAN PRENYLCYSTEINE CARBOXYL METHYLTRANSFERASE IS IN THE ENDOPLASMIC-RETICULUM

Prenylcysteine carboxyl methyltransferase (pcCMT) is the third of thre e enzymes that posttranslationally modify C-terminal CAAX motifs and t hereby target CAAX proteins to the plasma membrane. Here we report the molecular characterization and subcellular localization of the first mammalian (human myeloid) pcCMT. The deduced amino acid sequence of ma mmalian pcCMT predicts a multiple membrane-spanning protein with homol ogies to the yeast pcCMT, STE14, and the mammalian band 3 anion transp orter. The human gene complemented a ste14 mutant. pcCMT mRNAs were ub iquitously expressed in human tissues. An anti-pc-CMT antiserum detect ed a 33-kDa protein in myeloid cell membranes. Ectopically expressed r ecombinant pc-CMT had enzymatic activity identical to that observed in neutrophil membranes. Mammalian pcCMT was not expressed at the plasma membrane but rather restricted to the endoplasmic reticulum. Thus, th e final enzyme in the sequence that modifies CAAX motifs is located in membranes topologically removed from the CAAX protein target membrane .