The PPP3CA gene encodes a number of alternative calcineurin isoforms, some previously described (Guerini and Klee, 1989; Kincaid et al., 1990; Reuter et al., 2001) and some described here for the first time, which are likely to acquire alternative functions as a result of deleting functional amino acid domains due to differential splicing of the calcineurin primary transcript. Many of these splice variants delete portions or all of the catalytic domain [Figures 2(A) and (B)] and/or regulatory subunit b binding domain. Removal of exon 14 (e.g., in CNEX13-15) removes a 10 amino acid domain whose function is currently unknown [Figure 2(B)]. Interestingly, each PPP3CA isoform appears to retain its calmodulin-binding domain and thus retain the potential for calcium/calmodulin regulation. Expression studies demonstrate that CNEX1-3, 13-14, and 13-15 represent the major PPP3CA isoforms in brain and peripheral tissues. Other isoforms appear to be expressed at less than 1% of the levels of expression of these major isoforms. CNEX1-10 and 3-12 isoforms are expressed in brain only, where they are likely to participate in regulation of brain-specific calcineurin isoform activity. However, isoforms
