1Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park, Australia2Section on Genetic Disorders of Drug Metabolism, Human Genetics Branch, National Institute of Child Health & Human Development, Bethesda, Maryland, USA3Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee, UK4Department of Toxicology, University of Tubingen, Tubingen,Germany5Departmente de Biochimie Medicate, Centre Medicale Universitaire, University of Geneva, Geneva, Switzerland6Centre de Recherches en Endocrinologie Moleculaire, Le Centre Hospitaller de FUniversite Laval, Ste-Foy, Quebec, Canada7URA CNRS 1288, Universite Henri Poincare Nancy 1, Vandoeurvre-les-Nancy, France8Department of Pharmacology, University of Iowa, Iowa City, Iowa, USA9Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan10Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel11Laboratoire de Biochimie, UR Medicine Lyon Sud, Oullins, France12Department of Medicine and Molecular Genetics, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, New York, USA13Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond, Virginia, USA14Department of Biochemistry, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada15Department of Biochemistry, Trinity College, University of Dublin, Dublin, Ireland16Center for Environmental Genetics, and Department of Environmental Health, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA
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This review represents an update of the nomenclature system for the UDP glucuronosyltransferase gene superfamily, which is based on divergent evolution. Since the previous review in 1991, sequences of many related UDP glycosyltransferases from lower organisms have appeared in the database, which expand our database considerably. At latest count, in animals, yeast, plants and bacteria there are 110 distinct cDNAs/ genes whose protein products all contain a characteristic 'signature sequence' and, thus, are regarded as members of the same superfamily. Comparison of a relatedness tree of proteins leads to the definition of 33 families. It should be emphasized that at least six cloned UDP-GlcNAc N-acetylglucosaminyltransferases are not sufficiently homologous to be included as members of this superfamily and may represent an example of convergent evolution. For naming each gene, it is recommended that the root symbol UGT for human (Ugt for mouse and Drosophila), denoting 'UDP glycosyltransferase,' be followed by an Arabic number representing the family, a letter designating the subfamily, and an Arabic numeral denoting the individual gene within the family or subfamily, e.g. 'human UGT2B4' and 'mouse Vgt2b5'. We recommend the name 'UDP glycosyltransferase' because many of the proteins do not preferen- tially use UDP glucuronic acid, or their nucleotide sugar preference is unknown. Whereas the gene is italicized, the corresponding cDNA, transcript, protein and enzyme activity should be written with upper-case letters and without italics, e.g. 'human or mouse UGT1 Al.' The VGT1 gene (spanning>500 kb) contains at least 12 promoters/first exons, which can be spliced and joined with common exons 2 through 5, leading to different JV-terminal halves but identical C-terminal halves of the gene products; in this scheme each first exon is regarded as a distinct gene (e.g. UGT1A1, UGT1A2,... UGT1A12). When an orthologous gene between species cannot be identified with certainty, as occurs in the UGT2B subfamily, sequential naming of the genes is being carried out chronologically as they become characterized. We suggest that the Human Gene Nomenclature Guidelines (http://wwvy.gene.acl.ac.uk/nomenclature/guidelines.html) be used for all species other than the mouse and Drosophila. Thirty published human UGT1A1 mutant alleles responsible for clinical hyperbilirubinemias are listed herein, and given numbers following an asterisk (e.g. UGT1A1*3O) consistent with the Human Gene Nomenclature Guidelines. It is anticipated that this VGT gene nomenclature system will require updating on a regular basis.