UGT1A1

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. [provided by RefSeq]

UDP glucuronosyltransferase 1 family, polypeptide A1

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:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212).
Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867).
Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808).
Also catalyzes the glucuronidation 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 losartan, 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:18004212, PubMed:20610558).
Isoform 2
Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.

Biological Process acute-phase response Source:Ensembl
Biological Process animal organ regeneration Source:Ensembl
Biological Process bilirubin conjugation Source:Reactome
Biological Process biphenyl catabolic process Source:Ensembl
Biological Process cellular glucuronidation Source:UniProtKB5 Publications
Biological Process cellular response to estradiol stimulus Source:Ensembl
Biological Process cellular response to ethanol Source:Ensembl
Biological Process cellular response to glucocorticoid stimulus Source:Ensembl
Biological Process estrogen metabolic process Source:UniProtKB3 Publications
Biological Process flavone metabolic process Source:BHF-UCL1 Publication
Biological Process flavonoid glucuronidation Source:BHF-UCL1 Publication
Biological Process heterocycle metabolic process Source:BHF-UCL1 Publication
Biological Process liver development Source:Ensembl
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 negative regulation of steroid metabolic process Source:BHF-UCL1 Publication
Biological Process response to lipopolysaccharide Source:Ensembl
Biological Process response to nutrient Source:Ensembl
Biological Process response to starvation Source:Ensembl
Biological Process retinoic acid metabolic process Source:BHF-UCL1 Publication
Biological Process steroid metabolic process Source:BHF-UCL1 Publication
Biological Process xenobiotic glucuronidation Source:UniProtKB3 Publications
Biological Process xenobiotic metabolic process Source:Reactome

Endoplasmic reticulum membrane
Cytoplasm, perinuclear region

Gilbert syndrome (GILBS):
Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
Transient familial neonatal hyperbilirubinemia (HBLRTFN):
A condition characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants.
Crigler-Najjar syndrome 1 (CN1):
Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.
Crigler-Najjar syndrome 2 (CN2):
Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.

Helical: 491-507