title: Human Mpv17-like protein is localized in peroxisomes and regulates expression of antioxidant enzymes.
abstract: M-LP (Mpv17-like protein) is a protein that was initially identified in mouse tissues and shows high sequence homology with Mpv17 protein, a peroxisomal membrane protein involved in the development of early-onset glomerulosclerosis [R. Iida, T. Yasuda, E. Tsubota, H. Takatsuka, M. Masuyama, T. Matsuki, K. Kishi, M-LP, Mpv17-like protein, has a peroxisomal membrane targeting signal comprising a transmembrane domain and a positively charged loop and up-regulates expression of the manganese superoxide dismutase gene, J. Biol. Chem. 278 (2003) 6301-6306]. Here we report the identification and characterization of a human homolog of the M-LP (M-LPH) gene. The M-LPH gene is composed of four exons, extends over 14kb on chromosome 16p13.1, and is expressed as two alternatively spliced variants comprising four and three exons, respectively, which include open-reading frames encoding two distinct isoforms composed of 196 (M-LPH1) and 147 (M-LPH2) amino acids, respectively. These two variants were expressed ubiquitously in human tissues, however only M-LPH1 was detected at the protein level. Dual-color confocal analysis of COS-7 cells transfected with a green fluorescent protein-tagged M-LPH1 demonstrated that M-LPH1 is localized in peroxisomes. In order to elucidate the function of M-LPH1, we examined the mRNA levels of several enzymes involved in the metabolism of reactive oxygen species in COS-7 cells and found that transfection with M-LPH1 down-regulates expression of the plasma glutathione peroxidase and catalase genes. These results show the existence of the human homolog of M-LP and its participation in reactive oxygen species metabolism.
authors.affiliation: Division of Forensic Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. ireiko@fmsrsa.fukui-med.ac.jp
authors.forename: Reiko
authors.initials: R
authors.lastname: Iida
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yasuda
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tsubota
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Takatsuka
authors.forename: Takasumi
authors.initials: T
authors.lastname: Matsuki
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kishi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004798:Enzymes / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020675:Peroxisomes / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D000975:Antioxidants; D004798:Enzymes; C511128:MPV17L protein, human; D008565:Membrane Proteins; C065292:Mpv17 protein, mouse; D017382:Reactive Oxygen Species