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)
End	69,526,014 bp
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
	7363
	n/a
	ENSG00000156096
	n/a
	P06133
	n/a
	NM_001297615 ; NM_001297616 ; NM_021139
	n/a
	NP_001284544 ; NP_001284545 ; NP_066962
	n/a
	Wikidata
View/Edit Human

Last updated January 01, 2021

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.

Related Research Articles

Gilbert's syndrome (GS) is a mild liver disorder in which the liver does not properly process bilirubin. Many people never have symptoms. Occasionally a slight yellowish color of the skin or whites of the eyes may occur. Other possible symptoms include feeling tired, weakness, and abdominal pain.

Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.

Uridine 5'-diphospho-glucuronosyltransferase is a microsomal glycosyltransferase that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.

UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the UGT1A1 gene.

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltransferase-2B7 is encoded by the UGT2B7 gene.

UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.

UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the UGT1A10 gene.

UDP-glucuronosyltransferase 2B15 is an enzyme that in humans is encoded by the UGT2B15 gene.

UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the UGT1A3 gene.

UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4 gene.

Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 is an enzyme that in humans is encoded by the B3GAT3 gene.

UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is encoded by the UGT2B17 gene.

UDP glucuronosyltransferase 1 family, polypeptide A cluster, also known as UGT1A@, is a human gene.

UDP-glucuronosyltransferase 2B10 is an enzyme that in humans is encoded by the UGT2B10 gene.

Hyodeoxycholic acid, also known as 3α,6α-Dihydroxy-5β-cholan-24-oic acid or HDCA, is a secondary bile acid, one of the metabolic byproducts of intestinal bacteria. It differs from deoxycholic acid in that the 6α-hydroxyl is in the 12 position in the former. The 6α-hydroxyl group makes HDCA a hydrophilic acid, a property it shares with hyocholic acid. HDCA is present in mammalian species in different proportions. It is the main acid constituent of hog bile, and for this reason it was used industrially as precursor for steroid synthesis before total synthesis became practical.

UDP-glucuronosyltransferase 1-5 is an enzyme that in humans is encoded by the UGT1A5 gene.

UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene.

UDP glucuronosyltransferase 2 family, polypeptide B1, also known as UGT2B1, is an enzyme that in humans is encoded by the UGT2B1 gene.

UDP glucuronosyltransferase 1 family, polypeptide A7 is a protein that in humans is encoded by the UGT1A7 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000156096 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4".
↑ 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.
↑ 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.
↑ 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.
↑ 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.

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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000156096 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-3] "Entrez Gene: UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4".

[pmid3109396-4] 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.

[pmid7835904-5] 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.

[pmid17263731-6] 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.

[pmid12806625-7] 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.

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UGT2B4

Contents

Function

Related Research Articles

References

Further reading