Alternative titles; symbols
HGNC Approved Gene Symbol: UGT2B4
Cytogenetic location: 4q13.3 Genomic coordinates (GRCh38): 4:69,480,165-69,526,014 (from NCBI)
Jackson et al. (1987) cloned a human liver microsomal UDP-glucuronosyltransferase cDNA. By screening a liver library with a rat UGT2B1 cDNA, Jin et al. (1993) isolated cDNAs encoding UGT2B4, which they called UGT2B11, and UGT2B10 (600070). The deduced amino acid sequences shared greater than 76% sequence similarity with other known human liver UGT2B subfamily isoforms. The predicted 528-amino acid UGT2B4 protein contained an N-terminal signal peptide and a C-terminal transmembrane hydrophobic region. Mammalian cells expressing UGT2B4 produced a 51-kD protein that was recognized by a UGT-specific polyclonal antibody. The expressed protein catalyzed the glucuronidation of several polyhydroxylated estrogens and xenobiotics.
Monaghan et al. (1992) stated that the 5 members of subfamily 2 are probably derived from independent genes. Due to the difficulty in isolating suitable specific cDNA probes from the UGT2 members, Monaghan et al. (1992) used the polymerase chain reaction (PCR) in the chromosomal mapping of the steroid UGT gene encoding a bile acid UGT. Analysis of a panel of human/rodent somatic cell hybrids indicated that the gene, symbolized UGT2B, is located on human chromosome 4. Burchell et al. (1991) recommended that the symbol Udpgt-3 used by Krasnewich et al. (1987) be changed to Ugt2b.
Monaghan et al. (1992) used PCR to map the UGT2B4 gene to chromosome 4. The corresponding gene in the mouse was assigned to chromosome 5, which has a region of homology with human chromosome 4, by Krasnewich et al. (1987). By fluorescence in situ hybridization with a YAC containing all 3 genes, Monaghan et al. (1994) localized UGT2B4, UGT2B9 (also called UGT2B7; see 600068), and UGT2B15 (600069) to 4q13. They provisionally ordered the genes as UGT2B9--UGT2B4--UGT2B15.
Riedy et al. (2000) examined a genomic map spanning approximately 500 to 1000 kb in the 4q13 region. They placed UGT2B4 between UGT2B7 and UGT2B15. Also, access to a large reference DNA bank allowed them to calculate the allele frequencies for a single nucleotide polymorphism (SNP), Q458D, in UGT2B4 among 803 unrelated individuals representing 5 ethnic populations. The findings suggested a recent evolutionary history of gene duplication, mutation, and rearrangement.
The UDP-glucuronosyltransferases, a group of isoenzymes located primarily in hepatic endoplasmic reticulum and nuclear envelope, are encoded by a large multigene family that has evolved to produce catalysts with differing but overlapping substrate specificities. Two subfamilies are recognized by sequence identities (Burchell et al., 1991). UGT1 consists of at least 4 isoenzymes that catalyze the glucuronidation of phenols and bilirubin. All 4 map to chromosome 2 and probably derive from the same gene (UGT1; 191740). The UGT2 family contains at least 5 members catalyzing steroid or bile acid glucuronidation. Members of the subfamily share 65 to 90% amino acid sequence identity. However, unlike the phenol UGT cDNAs, where the high degree of identity is concentrated in the 3-prime region of the cDNA, the steroid UGTs have a high degree of sequence homology throughout the cDNA (summary by Monaghan et al., 1992).
Burchell, B., Nebert, D. W., Nelson, D. R., Bock, K. W., Iyanagi, T., Jansen, P. L. M., Lancet, T., Mulder, G. J., Chowdhury, J. R., Siest, G., Tephly, T. R., Mackenzie, P. I. The UDP-glucuronosyltransferase gene superfamily: suggested nomenclature based on evolutionary divergence. DNA Cell Biol. 10: 487-494, 1991. [PubMed: 1909870] [Full Text: https://doi.org/10.1089/dna.1991.10.487]
Jackson, M. R., McCarthy, L. R., Harding, D., Wilson, S., Coughtrie, M. W. H., Burchell, B. Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA. Biochem. J. 242: 581-588, 1987. [PubMed: 3109396] [Full Text: https://doi.org/10.1042/bj2420581]
Jin, C.-J., Miners, J. O., Lillywhite, K. J., Mackenzie, P. I. cDNA cloning and expression of two new members of the human liver UDP-glucuronosyltransferase 2B subfamily. Biochem. Biophys. Res. Commun. 194: 496-503, 1993. [PubMed: 8333863] [Full Text: https://doi.org/10.1006/bbrc.1993.1847]
Krasnewich, D., Kozak, C. A., Nebert, D. W., Mackenzie, P. I. Localization of UDP glucuronosyltransferase gene(s) on mouse chromosome 5. Somat. Cell Molec. Genet. 13: 179-182, 1987. [PubMed: 3105095] [Full Text: https://doi.org/10.1007/BF01534698]
Monaghan, G., Clarke, D. J., Povey, S., See, C. G., Boxer, M., Burchell, B. Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13. Genomics 23: 496-499, 1994. [PubMed: 7835904] [Full Text: https://doi.org/10.1006/geno.1994.1531]
Monaghan, G., Povey, S., Burchell, B., Boxer, M. Localization of a bile acid UDP-glucuronosyltransferase gene (UGT2B) to chromosome 4 using the polymerase chain reaction. Genomics 13: 908-909, 1992. [PubMed: 1639428] [Full Text: https://doi.org/10.1016/0888-7543(92)90188-x]
Riedy, M., Wang, J. Y., Miller, A. P., Buckler, A., Hall, J., Guida, M. Genomic organization of the UGT2b gene cluster on human chromosome 4q13. Pharmacogenetics 10: 251-260, 2000. [PubMed: 10803681] [Full Text: https://doi.org/10.1097/00008571-200004000-00006]