title: Identification and characterization of a human mitochondrial NAD kinase.
abstract: NAD kinase is the sole NADP(+) biosynthetic enzyme. Despite the great significance of NADP(+), to date no mitochondrial NAD kinase has been identified in human, and the source of human mitochondrial NADP(+) remains elusive. Here we present evidence demonstrating that a human protein of unknown function, C5orf33, is a human mitochondrial NAD kinase; this protein likely represents the missing source of human mitochondrial NADP(+). The C5orf33 protein exhibits NAD kinase activity, utilizing ATP or inorganic polyphosphate, and is localized in the mitochondria of human HEK293A cells. C5orf33 mRNA is more abundant than human cytosolic NAD kinase mRNA in almost all tissues examined. We further show by database searches that some animals and protists carry C5orf33 homologues as their sole NADP(+) biosynthetic enzyme, whereas plants and fungi possess no C5orf33 homologue. These observations provide insights into eukaryotic NADP(+) biosynthesis, which has pivotal roles in cells and organelles.
authors.affiliation: Laboratory of Basic and Applied Molecular Biotechnology, Division of Food and Biological Science, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ohashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kawai
authors.forename: Kousaku
authors.initials: K
authors.lastname: Murata
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D015153:Blotting, Western; D057809:HEK293 Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011122:Polyphosphates / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D011122:Polyphosphates; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; C581562:NADK2 protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase