The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms

We hake identified the human gene for member 3 of Solute Carrier family 8 (SLC8A3) by bioinformatic analysis of human genomic sequences. The gene is located on chromosome 14q24.2. and spans a region of about 150 kb. The full-length DNA complementary to RNA encoding the Na+/Ca2+ exchanger isoform 3 (NCX3). amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) from the human neuroblastoma SH-SY5Y RNA, includes seven exons and encodes a protein of about 100 kDa. RT-PCR analysis was performed in different tissues to determine the exon composition in the region encoding the large intracellular loop of the protein. The region Underwent modifications by alternative tissue-specific splicing. NCX3.2. including exon 4 but not exon 5. was found in human brain and in the neuroblastoma cell line. In human skeletal muscle two additional isoforms were identified: NCX3.3. including exons 4 and 5, and a truncated isoform (NCX3.4) produced by the skipping of both exons 3 and 4. The skipping causes a frame shift downstream of the exon 2 sequence. The new coding sequence of 25 amino acids terminates with a stop codon in exon 6. The NCX3.4 isoform (68 kDa) is truncated in the C-terminal portion of the domain first found in Drosophila Na+/Ca2+ exchanger domain (Calxbeta) and lacks the C-terminal hydrophobic segments. (C) 2002 Elsevier Science B.V. All rights reserved.