General Information of Drug-Metabolizing Enzyme (DME) (ID: DEF2WXN)

DME Name UDP-glucuronosyltransferase 1A3 (UGT1A3)
Synonyms UDP-glucuronosyltransferase family 1 member A3; UDP-glucuronosyltransferase 1-C; UDP-glucuronosyltransferase 1-3; UDPGT 1-3; UGT-1C; UGT1*3; UGT1-03; UGT1.3; UGT1A3; UGT1C
Gene Name UGT1A3
UniProt ID
UD13_HUMAN
INTEDE ID
DME0041
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
54659
EC Number EC: 2.4.1.17
Transferase
Glycosyltransferases
Hexosyltransferase
EC: 2.4.1.17
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MATGLQVPLPWLATGLLLLLSVQPWAESGKVLVVPIDGSHWLSMREVLRELHARGHQAVV
LTPEVNMHIKEENFFTLTTYAISWTQDEFDRHVLGHTQLYFETEHFLKKFFRSMAMLNNM
SLVYHRSCVELLHNEALIRHLNATSFDVVLTDPVNLCAAVLAKYLSIPTVFFLRNIPCDL
DFKGTQCPNPSSYIPRLLTTNSDHMTFMQRVKNMLYPLALSYICHAFSAPYASLASELFQ
REVSVVDILSHASVWLFRGDFVMDYPRPIMPNMVFIGGINCANRKPLSQEFEAYINASGE
HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Function This enzyme is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
KEGG Pathway
Ascorbate and aldarate metabolism (hsa00053 )
Chemical carcinogenesis (hsa05204 )
Drug metabolism - cytochrome P450 (hsa00982 )
Drug metabolism - other enzymes (hsa00983 )
Metabolic pathways (hsa01100 )
Metabolism of xenobiotics by cytochrome P450 (hsa00980 )
Pentose and glucuronate interconversions (hsa00040 )
Porphyrin and chlorophyll metabolism (hsa00860 )
Retinol metabolism (hsa00830 )
Steroid hormone biosynthesis (hsa00140 )
Reactome Pathway
NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis (R-HSA-9623433 )
Glucuronidation (R-HSA-156588 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
34 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ambrisentan DMD1QXW Pulmonary arterial hypertension BB01.0 Approved [1]
Anastrozole DMNP60F Breast cancer 2C60-2C65 Approved [2]
Atorvastatin DMF28YC Acute coronary syndrome BA41 Approved [3]
Baloxavir marboxil DM1UV7F Influenza virus infection 1E30-1E32 Approved [4]
Candesartan DMRK8OT Chronic heart failure BD1Z Approved [5]
Cerivastatin DMXCM7H Hyperlipidaemia 5C80 Approved [6]
Cyproheptadine DM92AH3 Allergic rhinitis CA08.0 Approved [7]
Darolutamide DMV7YFT Prostate cancer 2C82.0 Approved [8]
Deferasirox DM6ETS0 Beta thalassemia 3A50.2 Approved [9]
Dexibuprofen DMFYBD0 Ankylosing spondylitis FA92.0 Approved [5]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [10]
Empagliflozin DMRF9YK Type-1 diabetes 5A10 Approved [11]
Etodolac DM6WJO9 Osteoarthritis FA00-FA05 Approved [5]
Ezetimibe DM7A8TW Atherosclerosis BD40 Approved [12]
Flurbiprofen DMGN4BY Osteoarthritis FA00-FA05 Approved [5]
Gemfibrozil DMD8Q3J Hyperlipidaemia 5C80 Approved [13]
Hydromorphone DMHP21E Back pain ME84.Z Approved [14]
Ibuprofen DM8VCBE Dysmenorrhea GA34.3 Approved [5]
Irbesartan DMTP1DC Diabetic kidney disease GB61.Z Approved [5]
Ketotifen DM74XKS Allergic conjunctivitis 9A60.02 Approved []
Lamotrigine DM8SXYG Bipolar disorder 6A60 Approved [15]
Lorlatinib DMICDLV Non-small-cell lung cancer 2C25.Y Approved [16]
Losartan DM72JXH Diabetic kidney disease GB61.Z Approved [5]
Lovastatin DM9OZWQ Arteriosclerosis BD40 Approved [17]
Mitiglinide DMP8HEL Diabetic complication 5A2Y Approved [5]
Morphine DMRMS0L Advanced cancer 2A00-2F9Z Approved [7]
Naproxen DMZ5RGV Bursitis Approved [18]
PITAVASTATIN CALCIUM DM1UJO0 Dyslipidemia 5C80-5C81 Approved [19]
Retigabine DMGNYIH Behcet disease 4A62 Approved [20]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [17]
Telmisartan DMS3GX2 Hypertension BA00-BA04 Approved [21]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [22]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [23]
Vorinostat DMWMPD4 Adult acute monocytic leukemia Approved [24]
⏷ Show the Full List of 34 Approved Drug(s)
5 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
LCQ908 DMFLJHQ Familial chylomicronemia syndrome 5C80 Phase 3 [25]
MURAGLITAZAR DMG3NFZ N. A. N. A. Phase 3 [26]
Rivoglitazone DMBY31K Ocular inflammation 9C61.24 Phase 3 [27]
TAK-875 DMIM5AP Type-2 diabetes 5A11 Phase 3 [28]
Bevirimat DML2D8Q Human immunodeficiency virus infection 1C62 Phase 2 [29]
2 Discontinued Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Gavestinel DM8IL1U Nerve injury ND56.4 Discontinued in Phase 2 [5]
Licofelone DM7HLFD Osteoarthritis FA00-FA05 Discontinued in Phase 1 [30]

References

1 Clinical pharmacokinetics and drug-drug interactions of endothelin receptor antagonists in pulmonary arterial hypertension. J Clin Pharmacol. 2012 Dec;52(12):1784-805.
2 In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole. Br J Clin Pharmacol. 2010 Dec;70(6):854-69.
3 UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7.
4 FDA Label of Baloxavir marboxil. The 2020 official website of the U.S. Food and Drug Administration.
5 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
6 Cerivastatin, genetic variants, and the risk of rhabdomyolysis. Pharmacogenet Genomics. 2011 May;21(5):280-8.
7 Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos. 1998 Jun;26(6):507-12.
8 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
9 Deferasirox pharmacogenetic influence on pharmacokinetic, efficacy and toxicity in a cohort of pediatric patients. Pharmacogenomics. 2017 Apr;18(6):539-554.
10 Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
11 Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.
12 Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8.
13 Comprehensive pharmacogenomic study reveals an important role of UGT1A3 in montelukast pharmacokinetics. Clin Pharmacol Ther. 2018 Jul;104(1):158-168.
14 Opioid therapies and cytochrome p450 interactions. J Pain Symptom Manage. 2012 Dec;44(6 Suppl):S4-14.
15 Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica. 2009 May;39(5):355-63.
16 FDA label of Lorlatinib. The 2020 official website of the U.S. Food and Drug Administration.
17 Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
18 S-Naproxen and desmethylnaproxen glucuronidation by human liver microsomes and recombinant human UDP-glucuronosyltransferases (UGT): role of UGT2B7 in the elimination of naproxen. Br J Clin Pharmacol. 2005 Oct;60(4):423-33.
19 Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
20 Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos. 1999 May;27(5):605-12.
21 Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin. Drug Metab Dispos. 2012 Apr;40(4):825-35.
22 Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
23 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
24 Uridine 5'-diphospho-glucuronosyltransferase genetic polymorphisms and response to cancer chemotherapy. Future Oncol. 2010 Apr;6(4):563-85.
25 Pradigastat disposition in humans: in vivo and in vitro investigations. Xenobiotica. 2017 Dec;47(12):1077-1089.
26 Characterization of the UDP glucuronosyltransferase activity of human liver microsomes genotyped for the UGT1A1*28 polymorphism. Drug Metab Dispos. 2007 Dec;35(12):2270-80.
27 In vitro metabolism of rivoglitazone, a novel peroxisome proliferator-activated receptor gama agonist, in rat, monkey, and human liver microsomes and freshly isolated hepatocytes. Drug Metab Dispos. 2011 Jul;39(7):1311-9.
28 Disposition and metabolism of the G protein-coupled receptor 40 agonist TAK-875 (fasiglifam) in rats, dogs, and humans. Xenobiotica. 2019 Apr;49(4):433-445.
29 Bevirimat: a novel maturation inhibitor for the treatment of HIV-1 infection. Antivir Chem Chemother. 2008;19(3):107-13.
30 In vitro metabolism of 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl] acetic acid (licofelone, ML3000), an inhibitor of cyclooxygenase-1 and -2 and 5-lipoxygenase. Drug Metab Dispos. 2008 May;36(5):894-903.