UGT1A3

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. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq]

Full Name

UDP glucuronosyltransferase 1 family, polypeptide A3

Function

Isoform 1
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:18674515, PubMed:18719240, PubMed:23756265, PubMed:23288867, PubMed:24641623).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:23756265).
Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229, PubMed:18719240, PubMed:23288867).
Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265).
Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3, essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623).
Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonists losartan, candesartan and zolarsartan, which can inhibit the effect of angiotensin II (PubMed:18674515).
Isoform 2
Lacks UDP-glucuronosyltransferase (UGT) activity but acts as a negative regulator of isoform 1.

Biological Process

Biological Process bile acid secretion Source:UniProtKB1 Publication
Biological Process cellular glucuronidation Source:UniProtKB3 Publications
Biological Process estrogen metabolic process Source:UniProtKB1 Publication
Biological Process flavonoid glucuronidation Source:BHF-UCL1 Publication
Biological Process negative regulation of cellular glucuronidation Source:BHF-UCL
Biological Process negative regulation of fatty acid metabolic process Source:BHF-UCL
Biological Process negative regulation of glucuronosyltransferase activity Source:BHF-UCL
Biological Process retinoic acid metabolic process Source:BHF-UCL1 Publication
Biological Process vitamin D3 metabolic process Source:UniProtKB1 Publication
Biological Process xenobiotic glucuronidation Source:BHF-UCL1 Publication
Biological Process xenobiotic metabolic process Source:Reactome

Cellular Location

Endoplasmic reticulum membrane

Topology

Helical: 492-508