UGT2B4

Protein-coding gene in the species Homo sapiens
UGT2B4
Identifiers
AliasesUGT2B4, HLUG25, UDPGT2B4, UDPGTH1, UDPGTh-1, UGT2B11, UDP glucuronosyltransferase family 2 member B4
External IDsOMIM: 600067; MGI: 1919023; HomoloGene: 130717; GeneCards: UGT2B4; OMA:UGT2B4 - orthologs
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for UGT2B4
Genomic location for UGT2B4
Band4q13.3Start69,480,165 bp[1]
End69,526,014 bp[1]
Gene location (Mouse)
Chromosome 5 (mouse)
Chr.Chromosome 5 (mouse)[2]
Chromosome 5 (mouse)
Genomic location for UGT2B4
Genomic location for UGT2B4
Band5|5 E1Start87,064,497 bp[2]
End87,074,389 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • liver

  • right lobe of liver

  • gonad

  • testicle

  • left ventricle

  • right auricle

  • 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
SpeciesHumanMouse
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 MbChr 5: 87.06 – 87.07 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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. ^ a b c GRCh38: Ensembl release 89: ENSG00000156096 – Ensembl, May 2017
  2. ^ a b c 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.
  • v
  • t
  • e
2.4.1: Hexosyl-
transferases
Glucosyl-
Galactosyl-
Glucuronosyl-
Fucosyl-
Mannosyl-
2.4.2: Pentosyl-
transferases
Ribose
ADP-ribosyltransferase
Phosphoribosyltransferase
Other
Other
2.4.99: Sialyl
transferases


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