Molecular cloning and characterization of two novel truncated isoforms of human Na+/Ca2+ exchanger 3, expressed in fetal brain.

The human gene encoding the Na+/Ca2+ exchanger family member 3 (NCX3) undergoes extensive alternative splicing, with four variants previously identified. In this study, we report two novel alternative transcripts encoding two N-terminally truncated NCX3 proteins specifically expressed in human fetal brain. The identified transcripts, designated NCX3-tN.1 and NCX3-tN.2, are approximately 2.8 kb and 2.9 kb, respectively. The open reading frames (ORFs) are predicted to encode separately a 284 and a 298 amino acid (aa) polypeptide. Sequence analysis and bioinformatics reveal that NCX3-tN.1 and NCX3-tN.2 are the result of alternative splicing of the NCX3 gene. They have their own potential start codons and unique 5' untranslated regions (UTRs) that are different from those of the known NCX3 variants. The variants include a part of intron 2 of the original gene organization as their first exon (exon "a") at the 5' end of the novel transcripts. NCX3-tN.2 consists of six exons including exon "a" and exons 4, 6, 7, 8 and 9 of NCX3, while NCX3-tN.1 lacks exon 4, but is otherwise similar to NCX3-tN.2. Expression studies show that both variants can be translated into protein and NCX3-tN.1 seems more efficiently translated. Based on their structural features, NCX3-tN.1 and NCX3-tN.2 proteins are potentially involved in regulation of Na+/Ca2+ homeostasis.