UGT2B4

UGT2B4
Identifiers
Aliases	UGT2B4 , HLUG25, UDPGT2B4, UDPGTH1, UDPGTh-1, UGT2B11, UDP glucuronosyltransferase family 2 member B4
External IDs	OMIM: 600067 HomoloGene: 130717 GeneCards: UGT2B4
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q13.3 Start 69,480,165 bp [1] End 69,526,014 bp [1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity, transferring glycosyl groups • transferase activity • glucuronosyltransferase activity • retinoic acid binding • transferase activity, transferring hexosyl groups • UDP-glycosyltransferase activity Cellular component • integral component of membrane • organelle membrane • endoplasmic reticulum membrane • intracellular membrane-bounded organelle • endoplasmic reticulum • membrane Biological process • cellular glucuronidation • metabolism Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7363	n/a
Ensembl	ENSG00000156096	n/a
UniProt	P06133	n/a
RefSeq (mRNA)	NM_001297615 NM_001297616 NM_021139	n/a
RefSeq (protein)	NP_001284544 NP_001284545 NP_066962	n/a
Location (UCSC)	Chr 4: 69.48 – 69.53 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the UGT2B4 gene. ^{[3] [4] [5]}

Function

UGT2B4 is mainly involved in the glucuronidation of hyodeoxycholic acid, a bile acid, and catechol-estrogens, such as 17-epiestriol and 4-hydroxy-estrone. ^[6]

The expression of the UGT2B4 enzyme is upregulated by the farnesoid X receptor (FXR), a nuclear receptor which is activated by bile acids. ^[7] These same bile acids are substrates for the UGT2B4 enzyme. Hence upregulation of UGT2B4 by activated FXR provides a mechanism for the detection, conjugation and subsequent elimination of toxic bile acids.

References

1. GRCh38: Ensembl release 89: ENSG00000156096 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Entrez Gene: UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4".
4. Jackson MR, McCarthy LR, Harding D, Wilson S, Coughtrie MW, Burchell B (March 1987). "Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA". Biochem. J. 242 (2): 581–8. doi:10.1042/bj2420581. PMC   1147744 . PMID   3109396.
5. Monaghan G, Clarke DJ, Povey S, See CG, Boxer M, Burchell B (September 1994). "Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13". Genomics. 23 (2): 496–9. doi:10.1006/geno.1994.1531. PMID   7835904.
6. Barre L, Fournel-Gigleux S, Finel M, Netter P, Magdalou J, Ouzzine M (March 2007). "Substrate specificity of the human UDP-glucuronosyltransferase UGT2B4 and UGT2B7. Identification of a critical aromatic amino acid residue at position 33". FEBS J. 274 (5): 1256–64. doi: 10.1111/j.1742-4658.2007.05670.x . PMID   17263731. S2CID   27151203.
7. Barbier O, Torra IP, Sirvent A, Claudel T, Blanquart C, Duran-Sandoval D, Kuipers F, Kosykh V, Fruchart JC, Staels B (June 2003). "FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity". Gastroenterology. 124 (7): 1926–40. doi:10.1016/S0016-5085(03)00388-3. PMID   12806625.

Further reading

• Mackenzie PI, Owens IS, Burchell B, et al. (1997). "The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence". Pharmacogenetics. 7 (4): 255–69. doi:10.1097/00008571-199708000-00001. PMID   9295054.
• Kadlubar FF, Miller JA, Miller EC (1977). "Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis". Cancer Res. 37 (3): 805–14. PMID   13929.
• Ritter JK, Chen F, Sheen YY, et al. (1992). "Two human liver cDNAs encode UDP-glucuronosyltransferases with 2 log differences in activity toward parallel substrates including hyodeoxycholic acid and certain estrogen derivatives". Biochemistry. 31 (13): 3409–14. doi:10.1021/bi00128a015. PMID   1554722.
• Fournel-Gigleux S, Jackson MR, Wooster R, Burchell B (1989). "Expression of a human liver cDNA encoding a UDP-glucuronosyltransferase catalysing the glucuronidation of hyodeoxycholic acid in cell culture". FEBS Lett. 243 (2): 119–22. doi: 10.1016/0014-5793(89)80111-5 . PMID   2492950. S2CID   36610635.
• Jackson MR, McCarthy LR, Harding D, et al. (1987). "Cloning of a human liver microsomal UDP-glucuronosyltransferase cDNA". Biochem. J. 242 (2): 581–8. doi:10.1042/bj2420581. PMC   1147744 . PMID   3109396.
• Monaghan G, Clarke DJ, Povey S, et al. (1995). "Isolation of a human YAC contig encompassing a cluster of UGT2 genes and its regional localization to chromosome 4q13". Genomics. 23 (2): 496–9. doi:10.1006/geno.1994.1531. PMID   7835904.
• Jin CJ, Miners JO, Lillywhite KJ, Mackenzie PI (1993). "cDNA cloning and expression of two new members of the human liver UDP-glucuronosyltransferase 2B subfamily". Biochem. Biophys. Res. Commun. 194 (1): 496–503. doi:10.1006/bbrc.1993.1847. PMID   8333863.
• Babu SR, Lakshmi VM, Huang GP, et al. (1996). "Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolites. pH stability and synthesis by human and dog liver". Biochem. Pharmacol. 51 (12): 1679–85. doi:10.1016/0006-2952(96)00165-7. PMID   8687483.
• Monaghan G, Burchell B, Boxer M (1997). "Structure of the human UGT2B4 gene encoding a bile acid UDP-glucuronosyltransferase". Mamm. Genome. 8 (9): 692–4. doi:10.1007/s003359900539. PMID   9271674. S2CID   31839619.
• King CD, Rios GR, Assouline JA, Tephly TR (1999). "Expression of UDP-glucuronosyltransferases (UGTs) 2B7 and 1A6 in the human brain and identification of 5-hydroxytryptamine as a substrate". Arch. Biochem. Biophys. 365 (1): 156–62. doi:10.1006/abbi.1999.1155. PMID   10222050.
• Lévesque E, Beaulieu M, Hum DW, Bélanger A (1999). "Characterization and substrate specificity of UGT2B4 (E458): a UDP-glucuronosyltransferase encoded by a polymorphic gene". Pharmacogenetics. 9 (2): 207–16. PMID   10376768.
• Strassburg CP, Kneip S, Topp J, et al. (2000). "Polymorphic gene regulation and interindividual variation of UDP-glucuronosyltransferase activity in human small intestine". J. Biol. Chem. 275 (46): 36164–71. doi: 10.1074/jbc.M002180200 . PMID   10748067.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC   139241 . PMID   12477932.
• Barbier O, Torra IP, Sirvent A, et al. (2003). "FXR induces the UGT2B4 enzyme in hepatocytes: a potential mechanism of negative feedback control of FXR activity". Gastroenterology. 124 (7): 1926–40. doi:10.1016/S0016-5085(03)00388-3. PMID   12806625.
• Barbier O, Duran-Sandoval D, Pineda-Torra I, et al. (2003). "Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme". J. Biol. Chem. 278 (35): 32852–60. doi: 10.1074/jbc.M305361200 . PMID   12810707.
• Saeki M, Saito Y, Jinno H, et al. (2005). "Single nucleotide polymorphisms and haplotype frequencies of UGT2B4 and UGT2B7 in a Japanese population". Drug Metab. Dispos. 32 (9): 1048–54. PMID   15319348.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Barre L, Fournel-Gigleux S, Finel M, et al. (2007). "Substrate specificity of the human UDP-glucuronosyltransferase UGT2B4 and UGT2B7. Identification of a critical aromatic amino acid residue at position 33". FEBS J. 274 (5): 1256–64. doi: 10.1111/j.1742-4658.2007.05670.x . PMID   17263731. S2CID   27151203.