UGT1A1
| UDP glucuronosyltransferase 1 family, polypeptide A1 | |||||||||||
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| Identifiers | |||||||||||
| Symbols | UGT1A1 ; UGT1; GNT1; UGT1A; UDPGT; HUG-BR1; UGT1*1 | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 83117 | ||||||||||
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| Template:GNF Ortholog box | |||||||||||
| Species | Human | Mouse | |||||||||
| Entrez | n/a | n/a | |||||||||
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| RefSeq (mRNA) | n/a | n/a | |||||||||
| RefSeq (protein) | n/a | n/a | |||||||||
| Location (UCSC) | n/a | n/a | |||||||||
| PubMed search | n/a | n/a | |||||||||
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome.[1]
UGT1A1 is a gene associated with Crigler-Najjar syndrome, and a common splice variant is associated with serious side effects to the common chemotherapeutic drug irinotecan. The primary function of the gene's protein product is uridine diphospate glycosyltrasnferase 1 and is involved in the conversion of lipophilic molocules to water soluble substances suitable for excretion via substrate glycosylation.
Lack of expression of UGT1A1 in the neonatal liver is the major cause of jaundice in newborns. This jaundice is generally caused by massive breakdown of fetal blood cells which produces bilirubin which cannot be cleared if UGT1A1 is expressed at low levels or is absent. This type of jaundice can remedied by UV light exposure.
It transports bilirubin and phenol.
See also
External links
- UGT1A1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- UGT nomenclature homepage at flinders.edu.au
References
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. PMID 9295054.
- Tukey RH, Strassburg CP (2000). "Human UDP-glucuronosyltransferases: metabolism, expression, and disease". Annu. Rev. Pharmacol. Toxicol. 40: 581–616. doi:10.1146/annurev.pharmtox.40.1.581. PMID 10836148.
- Kadakol A, Ghosh SS, Sappal BS; et al. (2000). "Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype". Hum. Mutat. 16 (4): 297–306. doi:10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z. PMID 11013440.
- King CD, Rios GR, Green MD, Tephly TR (2001). "UDP-glucuronosyltransferases". Curr. Drug Metab. 1 (2): 143–61. PMID 11465080.
- Bosma PJ (2003). "Inherited disorders of bilirubin metabolism". J. Hepatol. 38 (1): 107–17. PMID 12480568.
- Innocenti F, Ratain MJ (2003). "Irinotecan treatment in cancer patients with UGT1A1 polymorphisms". Oncology (Williston Park, N.Y.). 17 (5 Suppl 5): 52–5. PMID 12800608.
- Lee W, Lockhart AC, Kim RB, Rothenberg ML (2005). "Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development". Oncologist. 10 (2): 104–11. doi:10.1634/theoncologist.10-2-104. PMID 15709212.