UGT1A9

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 enzyme encoded by this gene is active on phenols. [provided by RefSeq]

Full Name

UDP glucuronosyltransferase 1 family, polypeptide A9

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:12181437, PubMed:15472229, PubMed:15470161, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212).
Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229).
Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173).
Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515).
Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558).
Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212).
Isoform 2
Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.

Biological Process

Biological Process cellular glucuronidation Source:UniProtKB1 Publication
Biological Process flavone metabolic process Source:BHF-UCL1 Publication
Biological Process flavonoid glucuronidation Source:BHF-UCL1 Publication
Biological Process liver development Source:GO_Central1 Publication
Biological Process negative regulation of cellular glucuronidation Source:UniProtKB
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 xenobiotic glucuronidation Source:BHF-UCL1 Publication
Biological Process xenobiotic metabolic process Source:UniProtKB1 Publication

Cellular Location

Microsome
Endoplasmic reticulum membrane

Topology

Helical: 488-504