Cloning and characterisation of the first drug-metabolising canine UDP-glucuronosyltransferase of the 2B subfamily

Biochem Pharmacol. 2003 Apr 15;65(8):1251-9. doi: 10.1016/s0006-2952(03)00064-9.


Glucuronidation is a major route of clearance for a diverse set of both drug and endogenous substrates. The present study was undertaken to redress the lack of molecular information currently available on drug glucuronidation by the dog, a species widely used in metabolism studies by the pharmaceutical industry. A novel dog uridine diphosphate glucuronosyltransferase (UGT), designated UGT2B31 (GenBank Accession Number: AY135176), has been isolated from a dog cDNA library, expressed in V79 cells and characterised using various methods: (i) UGT2B31 sequence has been compared with mammalian UGT sequences using both sequence alignments and phylogenetic analysis; and (ii) the substrate specificity of UGT2B31 has been determined using functional analysis and compared with that obtained using UGT2B7 and dog liver microsomes. The following results were obtained: (i) sequence alignments between UGT2B31 and UGT2B15 gave the greatest degree of identity (76%); however, human UGT2B4, human UGT2B7, monkey UGT2B9 (all 75%), and rat UGT2B1 (73%) also gave a high degree of identity; (ii) phylogenetic analysis determined UGT2B31 to be most closely related to rat UGT2B1; (iii) UGT2B31 displayed a substrate specificity similar to human UGT2B7 and rat UGT2B1, catalysing the glucuronidation of phenols, opioids, and carboxylic acid-containing drugs; and (iv) UGT2B31 only formed morphine-3-glucuronide; however, kinetic analysis determined the K(m) of this reaction to be similar to that observed with UGT2B7 (both approximately 1300 microM). The results suggest that UGT2B31 plays a crucial role in drug detoxification by the dog and may be the canine equivalent of human UGT2B7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biotransformation
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Dogs
  • Gene Library
  • Glucuronosyltransferase / classification
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism
  • Humans
  • Liver / enzymology*
  • Lung
  • Mammals
  • Microsomes, Liver / metabolism
  • Molecular Sequence Data
  • Phylogeny
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transfection


  • Recombinant Proteins
  • Glucuronosyltransferase

Associated data

  • GENBANK/AY135176