title: The human SLC8A3 gene and the tissue-specific Na+/Ca2+ exchanger 3 isoforms.
abstract: We have 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(+)/Ca(2+) 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(+)/Ca(2+) exchanger domain (Calxbeta) and lacks the C-terminal hydrophobic segments.
authors.affiliation: Department of Biological Chemistry, University of Padova, Via G. Colombo, 3, 35121 Padua, Italy. nadia.gabellini@unipd.it
authors.forename: Nadia
authors.initials: N
authors.lastname: Gabellini
authors.forename: Stefania
authors.initials: S
authors.lastname: Bortoluzzi
authors.forename: Gian A
authors.initials: GA
authors.lastname: Danieli
authors.forename: Ernesto
authors.initials: E
authors.lastname: Carafoli
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D006801:Humans; D007438:Introns; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C101832:SLC38A3 protein, human; D019831:Sodium-Calcium Exchanger; D004247:DNA