UGT2B4

UGT2B4
Identifiers
Aliases	UGT2B4 , HLUG25, UDPGT2B4, UDPGTH1, UDPGTh-1, UGT2B11, UDP glucuronosyltransferase family 2 member B4
External IDs	OMIM: 600067; MGI: 1919023; HomoloGene: 130717; GeneCards: UGT2B4; OMA:UGT2B4 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) [1] Band 4q13.3 Start 69,480,165 bp [1] End 69,526,014 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 E1 Start 87,064,497 bp [2] End 87,074,389 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in liver right lobe of liver gonad testicle left ventricle right auricle of heart right ventricle myocardium islet of Langerhans myocardium of left ventricle Top expressed in left lobe of liver embryo lumbar subsegment of spinal cord right ventricle tibiofemoral joint sexually immature organism medial head of gastrocnemius muscle lumbar spinal ganglion stria vascularis carotid body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function glycosyltransferase activity transferase activity glucuronosyltransferase activity retinoic acid binding hexosyltransferase activity 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 71773 Ensembl ENSG00000156096 ENSMUSG00000035836 UniProt P06133 Q8R084 RefSeq (mRNA) NM_001297615 NM_001297616 NM_021139 NM_152811 RefSeq (protein) NP_001284544 NP_001284545 NP_066962 NP_690024 Location (UCSC) Chr 4: 69.48 – 69.53 Mb Chr 5: 87.06 – 87.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the UGT2B4 gene. ^{[5] [6] [7]}

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. ^[8]

The expression of the UGT2B4 enzyme is upregulated by the farnesoid X receptor (FXR), a nuclear receptor which is activated by bile acids. ^[9] 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. GRCm38: Ensembl release 89: ENSMUSG00000035836 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: UGT2B4 UDP glucuronosyltransferase 2 family, polypeptide B4".
6. 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.
7. 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.
8. 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.
9. 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. Bibcode:2002PNAS...9916899M. 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.