title: Genomic structure and alternative splicing of the insulin receptor tyrosine kinase substrate of 53-kDa protein.
abstract: Insulin receptor tyrosine kinase substrate of 53-kDa protein (IRSp53) is now known to be a key factor in cytoskeleton reorganization. The human IRSp53 was identified as a binding partner with DRPLA protein, a product of the gene responsible for a neurodegenerative disorder, dentatorubral pallidoluysian atrophy, as well as a binding partner with brain-specific angiogenesis inhibitor 1. Previous studies identified at least four isoforms (L-, M-, S- and T-forms) in human, where 511 amino acid residues from the N-terminus were identical, followed by unique sequences of 9-41 amino acid residues. As each isoform had a distinct function, the unique sequences at the C-terminus had a vital role in its function. Here we report that these isoforms were indeed generated by alternative splicing, which was established by experimental and computational studies on human and rodent genomes. Previous biochemical reports suggested that rodents may lack one of the isoforms (L-form). This study solved this issue, as a nucleotide substitution occurred at a splice donor site followed by a large deletion in the rodent genome compared with human, which made the generation of the L-form impossible. This study also revealed overlapping of the IRSp53 and AATK genes coded for by complementary strands.
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.|Department of Pediatrics, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyahara
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamura-Oho
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Department of Pediatrics, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hoshika
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan. myamada@nch.go.jp.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: C119539:BAIAP2 protein, human; D009419:Nerve Tissue Proteins