Human UGTs are composed of two gene families, UGT1 and UGT2, and three subfamilies that are designated UGT1A, UGT2A, and UGT2B. Within each family, individual enzymes, e.g., UGT2A1, UGT2B4, share at least 45% sequence homology and subfamily members, e.g., UGT1A1 and UGT1A3, share at least 60% homology. The human UGT1 gene locus is located on the long arm of chromosome 2, and the UGT2 genes are found on the long arm of chromosome 4. UGT2 enzymes are each conventionally encoded by separate genes, but, unusually, UGT1 enzymes share a common mRNA transcript that is differentially spliced. Consequently, all UGT1A isoforms share four common C-terminal exons and are distinguished by a variable exon 1 sequence. UGT2 enzymes also share more sequence homology in their
C-termini, and so substrate selectivity is believed to reside largely in the hypervariable N-terminal regions of UGT enzymes.98 The nomenclature for individual UGTisoforms follows the system established for the P450s, i.e., UGT1A1, UGT2B7, etc.
Was this article helpful?