Molecular Cloning of a Third Isoform of the Calmodulin-sensitive Plasma Membrane Ca2+-Transporting ATPase That Is Expressed Predominantly in Brain and Skeletal Muscle

A complementary DNA for a third isoform of the calmodulin-sensitive plasma membrane Ca-ATPase has been isolated from a rat brain cDNA library. The nucleotide sequence of the 5.1-kilobase pair cDNA has been determined, and the amino acid sequence of the protein, designated PMCA3, has been deduced. PMCA3 is 1159 amino acids in length and has an Mr of 127,300. It exhibits 81% and 85% amino acid identity, respectively, to isoforms 1 and 2 (PMCA1 and PMCA2) of the plasma membrane Ca-ATPase. The transcript encoding PMCA3 is similar to that of PMCA1 in that it contains a sequence in the 3'-untranslated region that has the potential to encode an alternative calmodulin binding domain and carboxyl terminus. The tissue distribution of mRNAs encoding isoforms 1, 2, and 3 has been determined by Northern blot hybridization analyses. PMCA1 mRNAs are expressed in all tissues examined, suggesting that this protein may serve as a housekeeping form of the enzyme. However, PMCA2 and PMCA3 mRNAs exhibit a high degree of tissue specificity. PMCA2 mRNAs are expressed predominantly in brain and heart, whereas PMCA3 mRNAs are expressed predominantly in brain and skeletal muscle.