Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily

Abstract

Several novel UDP glycosyltransferase (UGT) genes, mainly UDP glucuronosyltransferases, have been identified in the human, mouse and rat genomes and in other mammalian species. This review provides an update of the UGT nomenclature to include these new genes and prevent the confusion that arises when the same gene is given different names. The new genes are named following previously established recommendations, taking into consideration evolutionary relatedness and the names already in general usage in the literature. The mammalian UGT gene superfamily currently has 117 members that can be divided into four families, UGT1, UGT2, UGT3 and UGT8. The 5-exon genes of the UGT1 family each contain a unique first exon, plus four exons that are shared between the genes; the exons 1 appear to have evolved by a process of duplication, leading to the synthesis of proteins with identical carboxyl-terminal and variable amino-terminal domains. Exon-sharing is also seen with the 6-exon UGT2A1 and UGT2A2 genes. However, UGT2A3 and those of the UGT2B (six exons), UGT3 (seven exons) and UGT8 gene families (five or six exons) do not share exons and most likely were derived by a process of duplication of all exons in the gene. Most UGT1 and UGT8 enzymes have been characterized in detail; however, the catalytic functions of the UGT3A enzymes and several UGT2 enzymes remain to be characterized.

From differential induction of UDP-glucuronosyltransferases in rat liver to characterization of responsible ligand-activated transcription factors, and their multilevel crosstalk in humans

“…In addition, treatment of rats with fibrates led to their characterization as peroxisome proliferators [12], CYP4 family inducers [5], and identification of PPARα as the responsible LATF [13]. It was soon recognized that these inducers also differentially activated other xenobiotic-metabolizing enzymes (XMEs), for example, UGT supergene family members [14] which similar to CYPs are differentially induced in rat liver by aryl hydrocarbons, phenobarbital and fibrates [15][16][17]. Recognition of common LATF-binding response elements in the regulatory region of target genes suggests that Phase I and II XMEs, drug transporters (Phase III) as well as LATFs represent an evolutionary conserved detoxification system for lipid-soluble endo-and xenobiotics [5,11,18,19].…”

Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 and breast cancer risk in Africans

“…UGT1A1, a member of the UGT superfamily, is involved in the metabolism of estrogens and the detoxification of potential carcinogens [2,3], and is expressed in mammary tissue [4]. It is also the primary isoenzyme responsible for glucuronidation of bilirubin, an antioxidant in blood.…”

Characterization of UDP-Glucuronosyltransferases Involved in Glucuronidation of Diethylstilbestrol in Human Liver and Intestine

“…19 They are expressed in various tissues in a tissue-dependent manner. 17 Each isoform displays different substrate preferences, despite usually exhibiting overlapping substrate specificities.…”