title: Comparative genomics on Shisa orthologs.
abstract: WNT signaling molecules are implicated in a variety of human tumors, such as gastric cancer and colorectal cancer. FGFR2 gene, encoding FGF receptor 2, is amplified in human gastric and breast cancer. WNT and FGF signaling pathways network together during carcinogenesis and embryogenesis. Xenopus shisa is claimed to inhibit the post-translational maturation of wnt and fgf receptors. Here, we identified and characterized the rat Shisa (Tmem46) gene by using bioinformatics for comparative proteomics and comparative genomics analyses. Rat Shisa gene, consisting of two exons, was located within AC126002.4 genome sequence. Shisa gene at rat chromosome 15p12 was found to encode a type I transmembrane protein (295 aa), showing 99.3, 92.5, 81.7, 40.3 and 38.6% total-amino-acid identity with mouse Shisa, human SHISA, chicken shisa, Xenopus shisa and zebrafish shisa, respectively. The extracellular Cys-rich domain with eight Cys residues was conserved among vertebrate Shisa orthologs. The C-terminal cytoplasmic region was conserved among mammalian and chicken Shisa orthologs, but not in Xenopus and zebrafish Shisa orthologs. Human SHISA promoter and rat Shisa promoter were not conserved well. Function of human SHISA is predicted to be divergent from that of Xenopus shisa due to the protein evolution and the promoter evolution. This is the first report on the rat Shisa gene and on molecular evolution of Shisa orthologs.
authors.affiliation: M&M Medical BioInformatics, Hongo 113-0033, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Katoh
authors.forename: Masaru
authors.initials: M
authors.lastname: Katoh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D023281:Genomics; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D040901:Proteomics; D051381:Rats; D016415:Sequence Alignment
chemical_list: D008565:Membrane Proteins; C506190:Shisa2 protein, rat