title: Cloning and characterization of two human skeletal muscle alpha-actinin genes located on chromosomes 1 and 11.
abstract: Conserved sequences of dystrophin, beta-spectrin, and alpha-actinin were used to plan a set of degenerate oligonucleotide primers with which we amplified a portion of a human alpha-actinin gene transcript. Using this short clone as a probe, we isolated and characterized full-length cDNA clones for two human alpha-actinin genes (ACTN2 and ACTN3). These genes encode proteins that are structurally similar to known alpha-actinins with approximately 80% amino acid identity to each other and to the previously characterized human nonmuscle gene. ACTN2 is the human homolog of a previously characterized chicken gene while ACTN3 represents a novel gene product. Northern blot analysis demonstrated that ACTN2 is expressed in both skeletal and cardiac muscle, but ACTN3 expression is limited to skeletal muscle. As with other muscle-specific isoforms, the EF-hand domains in ACTN2 and ACTN3 are predicted to be incapable of binding calcium, suggesting that actin binding is not calcium sensitive. ACTN2 was mapped to human chromosome 1q42-q43 and ACTN3 to 11q13-q14 by somatic cell hybrid panels and fluorescent in situ hybridization. These results demonstrate that some of the isoform diversity of alpha-actinins is the result of transcription from different genetic loci.
authors.affiliation: Division of Genetics, Children's Hospital, Boston, Massachusetts.
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
authors.forename: T J
authors.initials: TJ
authors.lastname: Byers
authors.forename: J H
authors.initials: JH
authors.lastname: Knoll
authors.forename: F M
authors.initials: FM
authors.lastname: Boyce
authors.forename: G A
authors.initials: GA
authors.lastname: Bruns
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000185:Actinin / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D016189:Dystrophin / Q000235:genetics; D005453:Fluorescence; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013049:Spectrin / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D016189:Dystrophin; D012335:RNA, Ribosomal; D000185:Actinin; D013049:Spectrin; D004247:DNA