UDP-glucuronosyltransferase 1A3

Details

Name
UDP-glucuronosyltransferase 1A3
Synonyms
  • 2.4.1.17
  • GNT1
  • UDP-glucuronosyltransferase 1-3
  • UDP-glucuronosyltransferase 1-C
  • UDP-glucuronosyltransferase 1A isoform 3
  • UDPGT 1-3
  • UGT-1C
  • UGT1
  • UGT1-03
  • UGT1.3
  • UGT1*3
  • UGT1A3
  • UGT1C
Gene Name
UGT1A3
UniProtKB Entry
P35503Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0007065|UDP-glucuronosyltransferase 1A3
MATGLQVPLPWLATGLLLLLSVQPWAESGKVLVVPIDGSHWLSMREVLRELHARGHQAVV
LTPEVNMHIKEENFFTLTTYAISWTQDEFDRHVLGHTQLYFETEHFLKKFFRSMAMLNNM
SLVYHRSCVELLHNEALIRHLNATSFDVVLTDPVNLCAAVLAKYLSIPTVFFLRNIPCDL
DFKGTQCPNPSSYIPRLLTTNSDHMTFMQRVKNMLYPLALSYICHAFSAPYASLASELFQ
REVSVVDILSHASVWLFRGDFVMDYPRPIMPNMVFIGGINCANRKPLSQEFEAYINASGE
HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues
534
Molecular Weight
60337.835
Theoretical pI
8.28
GO Classification
Processes
bile acid secretion / estrogen metabolic process / vitamin D3 metabolic process / xenobiotic metabolic process
General Function
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:23288867, PubMed:23756265, 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)
Specific Function
enzyme binding
Pfam Domain Function
Signal Regions
1-28
Transmembrane Regions
492-508
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0017182|UDP-glucuronosyltransferase 1-3 (UGT1A3)
ATGGCCACAGGACTCCAGGTTCCCCTGCCGTGGCTGGCCACAGGACTGCTGCTTCTCCTC
AGTGTCCAGCCCTGGGCTGAGAGTGGAAAGGTGTTGGTGGTGCCCATTGATGGCAGCCAC
TGGCTCAGCATGCGGGAGGTCTTGCGGGAGCTCCATGCCAGAGGCCACCAGGCAGTGGTC
CTCACCCCAGAGGTGAATATGCACATCAAAGAAGAGAACTTTTTCACCCTGACAACCTAT
GCCATTTCGTGGACCCAGGATGAATTTGATCGCCATGTGCTGGGCCACACTCAACTGTAC
TTTGAAACAGAACATTTTCTGAAGAAATTTTTCAGAAGTATGGCAATGTTGAACAATATG
TCTTTGGTCTATCATAGGTCTTGTGTGGAGCTACTACATAATGAGGCCCTGATCAGGCAC
CTGAATGCTACTTCCTTTGATGTGGTTTTAACAGACCCCGTTAACCTCTGCGCGGCAGTG
CTGGCTAAGTACCTGTCGATTCCTACTGTGTTTTTTTTGAGGAACATTCCATGTGATTTA
GACTTTAAGGGCACACAGTGTCCAAACCCTTCCTCCTATATTCCTAGATTACTAACAACC
AATTCAGACCACATGACATTCATGCAAAGGGTCAAGAACATGCTCTACCCTCTGGCCCTG
TCCTACATTTGCCATGCTTTTTCTGCTCCTTATGCAAGCCTTGCCTCTGAGCTTTTTCAG
AGAGAGGTGTCAGTGGTGGATATTCTCAGTCATGCATCTGTGTGGCTGTTCCGAGGGGAC
TTTGTGATGGACTACCCCAGGCCAATCATGCCCAACATGGTCTTCATTGGGGGCATCAAC
TGTGCCAACAGGAAGCCACTATCTCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAA
CATGGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCT
ATGGCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGA
ACCCGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGAT
CTGCTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTAT
GAAAGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGAC
AATGCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACT
TCTGAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAAC
ATCATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTG
TTCTGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCAC
GACCTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTG
CTGACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGG
AAAAAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Chromosome Location
2
Locus
2q37.1
External Identifiers
ResourceLink
UniProtKB IDP35503
UniProtKB Entry NameUD13_HUMAN
GenBank Protein ID340135
GenBank Gene IDM84127
GeneCard IDUGT1A3
HGNC IDHGNC:12535
KEGG IDhsa:54659
NCBI Gene ID54659
General References
  1. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS: A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem. 1992 Feb 15;267(5):3257-61. [Article]
  2. Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC: Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics. 2001 Jun;11(4):357-68. [Article]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  4. Alonen A, Finel M, Kostiainen R: The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72. doi: 10.1016/j.bcp.2008.07.006. Epub 2008 Jul 12. [Article]
  5. Bellemare J, Rouleau M, Girard H, Harvey M, Guillemette C: Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro. Drug Metab Dispos. 2010 Oct;38(10):1785-9. doi: 10.1124/dmd.110.034835. Epub 2010 Jul 7. [Article]
  6. Girard H, Levesque E, Bellemare J, Journault K, Caillier B, Guillemette C: Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity. Pharmacogenet Genomics. 2007 Dec;17(12):1077-89. [Article]
  7. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
  8. Menard V, Girard H, Harvey M, Perusse L, Guillemette C: Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population. Hum Mutat. 2009 Apr;30(4):677-87. doi: 10.1002/humu.20946. [Article]

Associated Data

Bio-Entities
Bio-EntityType
UDP-glucuronosyltransferase 1A3 (Humans)protein
primary
UDP-glucuronosyltransferases (UGTs) (Humans)protein
UDP-glucuronosyltransferase 1 family (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Candesartan cilexetilapprovedunknownenzymesubstrateDetails
Irbesartanapproved, investigationalunknownenzymesubstrateDetails
LosartanapprovedunknownenzymesubstrateDetails
Etodolacapproved, investigational, vet_approvedunknownenzymesubstrateDetails
Flurbiprofenapproved, investigationalunknownenzymesubstrateDetails
IbuprofenapprovedunknownenzymesubstrateDetails
Hydromorphoneapproved, illicitnoenzymesubstrateDetails
MitiglinideinvestigationalunknownenzymesubstrateDetails
LicofeloneinvestigationalunknownenzymesubstrateDetails
GavestinelinvestigationalunknownenzymesubstrateDetails
EltrombopagapprovedunknownenzymesubstrateDetails
Ambrisentanapproved, investigationalunknownenzymesubstrateDetails
Troglitazoneapproved, investigational, withdrawnunknownenzymesubstrateDetails
Morphineapproved, investigationalnoenzymesubstrateDetails
EzetimibeapprovedunknownenzymesubstrateDetails
MuraglitazarinvestigationalunknownenzymesubstrateDetails
CyproheptadineapprovedunknownenzymesubstrateDetails
Ezogabineapproved, investigationalunknownenzymesubstrateDetails
PitavastatinapprovedunknownenzymesubstrateDetails
AtorvastatinapprovednoenzymesubstrateDetails
Lovastatinapproved, investigationalunknownenzymesubstrateDetails
SimvastatinapprovedunknownenzymesubstrateDetails
Flunitrazepamapproved, illicitunknownenzymeinhibitorDetails
FluvastatinapprovedunknownenzymesubstrateDetails
Valproic acidapproved, investigationalunknownenzymesubstrateDetails
Delafloxacinapproved, investigationalnoenzymesubstrateDetails
Naldemedineapproved, investigationalnoenzymesubstrateDetails
Enasidenibapproved, investigationalunknownenzymesubstrateDetails
CandesartanexperimentalunknownenzymesubstrateDetails
Letermovirapproved, investigationalnoenzymesubstrateDetails
Nalmefeneapproved, investigational, withdrawnnoenzymesubstrateDetails
DolutegravirapprovednoenzymesubstrateDetails
DovitinibinvestigationalunknownenzymeinhibitorDetails
Deferasiroxapproved, investigationalunknownenzymeinhibitorDetails
Dexibuprofenapproved, investigationalunknownenzymesubstrateDetails
Baloxavir marboxilapproved, investigationalnoenzymesubstrateDetails
Telmisartanapproved, investigationalunknownenzymesubstrateDetails
GemfibrozilapprovedunknownenzymesubstrateinhibitorDetails
Lorlatinibapproved, investigationalunknownenzymesubstrateDetails
Naproxenapproved, vet_approvedunknownenzymesubstrateDetails
Diclofenacapproved, vet_approvedunknownenzymesubstrateDetails
Loratadineapproved, investigationalunknownenzymeDetails
Anastrozoleapproved, investigationalunknownenzymesubstrateDetails
EthinylestradiolapprovedunknownenzymeDetails
Selumetinibapproved, investigationalnoenzymeDetails
EmpagliflozinapprovedunknownenzymesubstrateDetails
KetotifenapprovedunknownenzymesubstrateDetails
FebuxostatapprovednoenzymesubstrateDetails
MirabegronapprovednoenzymesubstrateDetails
Nandrolone decanoateapproved, illicitunknownenzymesubstrateDetails
Tecovirimatapproved, investigationalunknownenzymesubstrateDetails
Dronabinolapproved, illicitnoenzymesubstrateDetails
Desvenlafaxineapproved, investigationalnoenzymesubstrateDetails
Vamoroloneapproved, investigationalnoenzymesubstrateDetails
Iptacopanapproved, investigationalnoenzymesubstrateDetails
Elafibranorapproved, investigationalunknownenzymesubstrateDetails
Lamotrigineapproved, investigationalunknownenzymesubstrateDetails
Ritonavirapproved, investigationalnoenzymeinducerDetails
Curcumin sulfateexperimentalunknownenzymeinhibitorDetails
Primidoneapproved, vet_approvedunknownenzymeinducerDetails
Estradiolapproved, investigational, vet_approvedunknownenzymesubstrateinducerDetails
Apomorphineapproved, investigationalunknownenzymesubstrateDetails
Fostemsavirapproved, investigationalunknownenzymesubstrateDetails
TerbutalineapprovedunknownenzymesubstrateDetails
Pindololapproved, investigationalunknownenzymesubstrateDetails
Ibrexafungerpapproved, investigationalunknownenzymesubstrateDetails
Elagolixapproved, investigationalnoenzymesubstrateDetails
Migalastatapproved, investigationalunknownenzymesubstrateDetails