title: Molecular cloning and characterization of two novel truncated isoforms of human Na+/Ca2+ exchanger 3, expressed in fetal brain.
abstract: 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.
authors.affiliation: Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Lindgren
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Susanne
authors.initials: S
authors.lastname: Heller
authors.forename: Hanna
authors.initials: H
authors.lastname: Berglind
authors.forename: Monica
authors.initials: M
authors.lastname: Nistér
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; 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* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C101832:SLC38A3 protein, human; D019831:Sodium-Calcium Exchanger