Alternative splicing of exons encoding the calmodulin-binding domains and C termini of plasma membrane Ca(2+)-ATPase isoforms 1, 2, 3, and 4.

Rat plasma membrane Ca(2+)-ATPase (PMCA) mRNAs were examined by S1 nuclease protection (isoform 1) and polymerase chain reaction (isoforms 1, 2, 3, and 4) and the corresponding genes were analyzed to determine the tissue-specific splicing patterns involving exons encoding the calmodulin-binding domains and C termini. Splicing of PMCA1 involves a single 154-nucleotide exon that can be either included or excluded; when the exon is included four different splice donor sites, at positions 87, 114, 152, and 154, can be utilized. PMCA2 mRNAs are generated either by the inclusion of a 172-nucleotide exon, by the inclusion of both the 172-nucleotide exon and a 55-nucleotide exon, or by the exclusion of both exons. Four PMCA3 mRNAs arise by alternative splicing of a 154-nucleotide exon, in patterns that are analogous to those of PMCA1, and additional mRNAs are generated by the inclusion of a 68-nucleotide exon immediately before the 154-nucleotide exon. The simplest splicing pattern occurs in PMCA4, where a single 175-nucleotide exon is either included or excluded. The alternative mRNAs for each of the four genes are expressed in a tissue-specific manner and encode enzyme variants with different combinations of calmodulin-binding domains and C termini.