THE UDP GLYCOSYLTRANSFERASE GENE SUPERFAMILY - RECOMMENDED NOMENCLATURE UPDATE BASED ON EVOLUTIONARY DIVERGENCE

This review cc represents an update of the nomenclature system for the UDP glucuronosyltransferase gene superfamily, which is based on diver gent evolution. Since the previous review in 1991, sequences of many r elated 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/g enes whose protein products all contain a characteristic 'signature se quence' and, thus, are regarded as members of the same superfamily, Co mparison of a relatedness tree of proteins leads to the definition of 33 families, It should be emphasized that at least six cloned UDP-GlcN Ac N-acetylglucosaminyltransferases are not sufficiently homologous to be included as members of this superfamily and may represent an examp le of convergent evolution, For naming each gene, it is recommended th at the root symbol UGT for human (Ugt for mouse and Drosophila), denot ing 'UDP glycosyltransferase,' be followed by an Arabic number represe nting the family, a letter designating the subfamily, and an Arabic nu meral denoting the individual gene within the family or subfamily, e.g . 'human UGT2B4' and 'mouse Ugt2b5'. We recommend the name 'UDP glycos yltransferase' because many of the proteins do not preferentially use UDP glucuronic acid, or their nucleotide sugar preference is unknown. Whereas the gene is italicized, the corresponding cDNA, transcript, pr otein and enzyme activity should be written with upper-case letters an d without italics, e.g. 'human or mouse UGT1A1. 'The UGT1 gene (spanni ng > 500 kb) contains at least 12 promoters/first exons, which call be spliced and joined with common exons 2 through 5, leading to differen t N-terminal halves but identical C-terminal halves of the gene produc ts; in this scheme each first exon is regarded as a distinct gene (e.g . UGT1A1, UGT1A2, ... UGT1A12). When an orthologous gene between speci es cannot be identified with certainty, as occurs in the UGT2B subfami ly, sequential naming of the genes is being carried out chronologicall y as they become characterized, We suggest that the Human Gene Nomencl ature Guidelines //www.gene.acl.ac.uk/nomenclature/guidelines.html) be used for all species other than the mouse and Drosophila. Thirty publ ished human UGT1A1 mutant alleles responsible for clinical hyperbiliru binemias are listed herein, and given numbers following an asterisk (e .g. UGT1A130:) consistent with the Human Gene Nomenclature Guidelines . It is anticipated that this UGT gene nomenclature system will requir e updating on a regular basis.