UD13_HUMAN
ID UD13_HUMAN Reviewed; 534 AA.
AC P35503; B8K287;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=UDP-glucuronosyltransferase 1A3 {ECO:0000303|PubMed:15472229, ECO:0000303|PubMed:18719240};
DE Short=UGT1A3;
DE EC=2.4.1.17 {ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:23756265, ECO:0000269|PubMed:24641623};
DE AltName: Full=UDP-glucuronosyltransferase 1-3;
DE Short=UDPGT 1-3;
DE Short=UGT1*3;
DE Short=UGT1-03;
DE Short=UGT1.3;
DE AltName: Full=UDP-glucuronosyltransferase 1-C;
DE Short=UGT-1C;
DE Short=UGT1C;
DE AltName: Full=UDP-glucuronosyltransferase 1A isoform 3;
DE Flags: Precursor;
GN Name=UGT1A3 {ECO:0000312|HGNC:HGNC:12535}; Synonyms=GNT1, UGT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1339448; DOI=10.1016/s0021-9258(19)50724-4;
RA Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T.,
RA Owens I.S.;
RT "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-
RT glucuronosyltransferase isozymes with identical carboxyl termini.";
RL J. Biol. Chem. 267:3257-3261(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11434514; DOI=10.1097/00008571-200106000-00011;
RA Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K., Kubota S.,
RA Carvalho S., Pennington M.W., Owens I.S., Popescu N.C.;
RT "Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1
RT gene complex locus.";
RL Pharmacogenetics 11:357-368(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Guillemette C., Levesque E., Girard H., Bernard O.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=15472229; DOI=10.1210/jc.2004-0331;
RA Lepine J., Bernard O., Plante M., Tetu B., Pelletier G., Labrie F.,
RA Belanger A., Guillemette C.;
RT "Specificity and regioselectivity of the conjugation of estradiol, estrone,
RT and their catecholestrogen and methoxyestrogen metabolites by human uridine
RT diphospho-glucuronosyltransferases expressed in endometrium.";
RL J. Clin. Endocrinol. Metab. 89:5222-5232(2004).
RN [6]
RP FUNCTION (ISOFORM 2), CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=18004212; DOI=10.1097/fpc.0b013e3282f1f118;
RA Girard H., Levesque E., Bellemare J., Journault K., Caillier B.,
RA Guillemette C.;
RT "Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative
RT splicing mechanism leading to nine additional UGT1A proteins that act as
RT regulators of glucuronidation activity.";
RL Pharmacogenet. Genomics 17:1077-1089(2007).
RN [7]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=17179145; DOI=10.1074/jbc.m609417200;
RA Operana T.N., Tukey R.H.;
RT "Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and
RT heterodimerization analysis by fluorescence resonance energy transfer and
RT co-immunoprecipitation.";
RL J. Biol. Chem. 282:4821-4829(2007).
RN [8]
RP FUNCTION (ISOFORM 1).
RX PubMed=18674515; DOI=10.1016/j.bcp.2008.07.006;
RA Alonen A., Finel M., Kostiainen R.;
RT "The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards
RT N2 in the tetrazole ring of losartan, candesartan, and zolarsartan.";
RL Biochem. Pharmacol. 76:763-772(2008).
RN [9]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBSTRATE SPECIFICITY.
RX PubMed=18719240; DOI=10.1124/dmd.108.022731;
RA Itaeaho K., Mackenzie P.I., Ikushiro S., Miners J.O., Finel M.;
RT "The configuration of the 17-hydroxy group variably influences the
RT glucuronidation of beta-estradiol and epiestradiol by human UDP-
RT glucuronosyltransferases.";
RL Drug Metab. Dispos. 36:2307-2315(2008).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [11]
RP FUNCTION (ISOFORM 2), AND SUBUNIT.
RX PubMed=20610558; DOI=10.1124/dmd.110.034835;
RA Bellemare J., Rouleau M., Girard H., Harvey M., Guillemette C.;
RT "Alternatively spliced products of the UGT1A gene interact with the
RT enzymatically active proteins to inhibit glucuronosyltransferase activity
RT in vitro.";
RL Drug Metab. Dispos. 38:1785-1789(2010).
RN [12]
RP FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX PubMed=23756265; DOI=10.1124/dmd.113.052613;
RA Perreault M., Gauthier-Landry L., Trottier J., Verreault M., Caron P.,
RA Finel M., Barbier O.;
RT "The Human UDP-glucuronosyltransferase UGT2A1 and UGT2A2 enzymes are highly
RT active in bile acid glucuronidation.";
RL Drug Metab. Dispos. 41:1616-1620(2013).
RN [13]
RP FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX PubMed=23288867; DOI=10.1124/dmd.112.049072;
RA Sneitz N., Vahermo M., Mosorin J., Laakkonen L., Poirier D., Finel M.;
RT "Regiospecificity and stereospecificity of human UDP-
RT glucuronosyltransferases in the glucuronidation of estriol, 16-epiestriol,
RT 17-epiestriol, and 13-epiestradiol.";
RL Drug Metab. Dispos. 41:582-591(2013).
RN [14]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=24641623; DOI=10.1210/en.2013-2013;
RA Wang Z., Wong T., Hashizume T., Dickmann L.Z., Scian M., Koszewski N.J.,
RA Goff J.P., Horst R.L., Chaudhry A.S., Schuetz E.G., Thummel K.E.;
RT "Human UGT1A4 and UGT1A3 conjugate 25-hydroxyvitamin D3: metabolite
RT structure, kinetics, inducibility, and interindividual variability.";
RL Endocrinology 155:2052-2063(2014).
RN [15]
RP VARIANTS ARG-11; ALA-47; VAL-158 AND VAL-270.
RX PubMed=19204906; DOI=10.1002/humu.20946;
RA Menard V., Girard H., Harvey M., Perusse L., Guillemette C.;
RT "Analysis of inherited genetic variations at the UGT1 locus in the French-
RT Canadian population.";
RL Hum. Mutat. 30:677-687(2009).
CC -!- FUNCTION: [Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes
CC phase II biotransformation reactions in which lipophilic substrates are
CC conjugated with glucuronic acid to increase the metabolite's water
CC solubility, thereby facilitating excretion into either the urine or
CC bile (PubMed:15472229, PubMed:18674515, PubMed:18719240,
CC PubMed:23756265, PubMed:23288867, PubMed:24641623). Essential for the
CC elimination and detoxification of drugs, xenobiotics and endogenous
CC compounds (PubMed:23756265). Catalyzes the glucuronidation of
CC endogenous estrogen hormones such as estradiol and estrone
CC (PubMed:15472229, PubMed:18719240, PubMed:23288867). Contributes to
CC bile acid (BA) detoxification by catalyzing the glucuronidation of BA
CC substrates, which are natural detergents for dietary lipids absorption
CC (PubMed:23756265). Involved in the glucuronidation of calcidiol, which
CC is the major circulating form of vitamin D3, essential for the
CC regulation of calcium and phosphate homeostasis (PubMed:24641623).
CC Involved in the glucuronidation of the AGTR1 angiotensin receptor
CC antagonists losartan, candesartan and zolarsartan, which can inhibit
CC the effect of angiotensin II (PubMed:18674515).
CC {ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18674515,
CC ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:23756265, ECO:0000269|PubMed:24641623}.
CC -!- FUNCTION: [Isoform 2]: Lacks UDP-glucuronosyltransferase (UGT) activity
CC but acts as a negative regulator of isoform 1.
CC {ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:20610558}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor
CC beta-D-glucuronoside + H(+) + UDP; Xref=Rhea:RHEA:21032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132367, ChEBI:CHEBI:132368; EC=2.4.1.17;
CC Evidence={ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:18674515,
CC ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:23756265, ECO:0000269|PubMed:24641623};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:18004212, ECO:0000305|PubMed:18674515,
CC ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:23288867,
CC ECO:0000305|PubMed:24641623};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52460,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136641;
CC Evidence={ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52461;
CC Evidence={ECO:0000305|PubMed:15472229, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol
CC 17-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52464,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:82961;
CC Evidence={ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52465;
CC Evidence={ECO:0000305|PubMed:15472229, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-
CC estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52868, ChEBI:CHEBI:15378, ChEBI:CHEBI:17160,
CC ChEBI:CHEBI:57529, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223;
CC Evidence={ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + UDP-alpha-D-glucuronate = estrone 3-O-(beta-D-
CC glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52476, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136634; Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52477;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + UDP-alpha-D-glucuronate =
CC chenodeoxycholoyl-24-O-(beta-D-glucuronate) + UDP;
CC Xref=Rhea:RHEA:52940, ChEBI:CHEBI:36234, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136899;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52941;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholate + UDP-alpha-D-glucuronate = deoxycholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52948, ChEBI:CHEBI:23614,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136901;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52949;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + UDP-alpha-D-glucuronate = lithocholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52952, ChEBI:CHEBI:29744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136902;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52953;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyodeoxycholate + UDP-alpha-D-glucuronate = hyodeoxycholoyl-
CC 24-O-(beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52956,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:58875,
CC ChEBI:CHEBI:136903; Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52957;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyocholate + UDP-alpha-D-glucuronate = hyocholoyl-24-O-(beta-
CC D-glucuronate) + UDP; Xref=Rhea:RHEA:52960, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:133661, ChEBI:CHEBI:136904;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52961;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcidiol + UDP-alpha-D-glucuronate = calcidiol 25-O-(beta-D-
CC glucuronide) + H(+) + UDP; Xref=Rhea:RHEA:55840, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17933, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:139277; Evidence={ECO:0000269|PubMed:24641623};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55841;
CC Evidence={ECO:0000305|PubMed:24641623};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=losartan + UDP-alpha-D-glucuronate = losartan-2-N-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63720, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149504, ChEBI:CHEBI:149507;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63721;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=candesartan + UDP-alpha-D-glucuronate = candesartan-2-N-beta-
CC D-glucuronide + UDP; Xref=Rhea:RHEA:63728, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149509, ChEBI:CHEBI:149523;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63729;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UDP-alpha-D-glucuronate + zolasartan = UDP + zolarsartan-2-N-
CC beta-D-glucuronide; Xref=Rhea:RHEA:63748, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149524, ChEBI:CHEBI:149528;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63749;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=47 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=35 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:15472229};
CC KM=77 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:15472229};
CC KM=479 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=32 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 2) {ECO:0000269|PubMed:15472229};
CC KM=587 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=222 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 2) {ECO:0000269|PubMed:15472229};
CC KM=49 uM for 2-methoxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=250 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=66.7 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=34.2 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=3.95 uM for calcidiol (when assaying glucuronidation at position
CC 25) {ECO:0000269|PubMed:24641623};
CC KM=5.9 uM for calcidiol (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:24641623};
CC KM=9.35 uM for 5,6-trans-calcidiol (when assaying glucuronidation at
CC position 25) {ECO:0000269|PubMed:24641623};
CC KM=35.9 uM for losartan (when assaying glucuronidation at position N2
CC of the tetrazole ring) {ECO:0000269|PubMed:18674515};
CC Vmax=39 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=13 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=50 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-D-
CC glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1342 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=39 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 2-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=41 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=28 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 2-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=154 pmol/min/mg enzyme for the formation of 2-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=653 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=86.1 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=683 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=26 pmol/min/mg enzyme for the formation of 17alpha-estradiol 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=1.74 pmol/min/mg enzyme for the formation of calcidiol 25-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:24641623};
CC Vmax=0.56 pmol/min/mg enzyme for the formation of calcidiol 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:24641623};
CC Vmax=0.22 pmol/min/mg enzyme for the formation of 5,6-trans-calcidiol
CC 25-O-(beta-D-glucuronate) {ECO:0000269|PubMed:24641623};
CC Vmax=225.7 pmol/min/mg enzyme for the formation of losartan N2-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:18674515};
CC Note=Some kinetic parameters were assessed using commercial enzymes,
CC which may represent a mix of both active and inactive protein forms,
CC and therefore modify the kinetic values.
CC {ECO:0000305|PubMed:24641623};
CC -!- SUBUNIT: Homodimer (PubMed:17179145). Homooligomer (Probable).
CC Interacts with UGT1A1, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and
CC UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts
CC with isoform 2/i2 suggesting that oligomerization is involved in
CC negative regulation of transferase activity by isoform 2. Isoform 1
CC also interacts with respective i2 isoforms of UGT1A1, UGT1A4, UGT1A6,
CC UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).
CC {ECO:0000269|PubMed:17179145, ECO:0000269|PubMed:20610558,
CC ECO:0000305|PubMed:20610558}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:17179145}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=i1 {ECO:0000303|PubMed:18004212};
CC IsoId=P35503-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A3s;
CC IsoId=P35503-3; Sequence=VSP_053959;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in liver, kidney, colon,
CC esophagus and small intestine. {ECO:0000269|PubMed:18004212}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver, kidney and colon.
CC Not expressed in esophagus and small intestine.
CC {ECO:0000269|PubMed:18004212}.
CC -!- MISCELLANEOUS: UGT1A3 isoform is part of the UGT1A complex locus which
CC displays alternative use of promoters, first exons and terminal exons.
CC The locus is defined by 13 first exons, which are alternatively spliced
CC to 3 other common exons and 2 alternative terminal exons 5. From the 27
CC possible mRNA isoforms, 9 produce functionally active polypeptides
CC (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1
CC (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to
CC 9 additional alternatively spliced products termed isoforms i2 and
CC which lack transferase activity. {ECO:0000269|PubMed:18004212}.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; M84127; AAA92020.1; -; Genomic_DNA.
DR EMBL; M84124; AAA61247.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M84122; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; M84123; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; AF297093; AAG30423.1; -; Genomic_DNA.
DR EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQ364248; ABC96772.1; -; mRNA.
DR CCDS; CCDS2509.1; -. [P35503-1]
DR PIR; D42586; D42586.
DR RefSeq; NP_061966.1; NM_019093.2. [P35503-1]
DR AlphaFoldDB; P35503; -.
DR SMR; P35503; -.
DR BioGRID; 120088; 3.
DR IntAct; P35503; 7.
DR STRING; 9606.ENSP00000418532; -.
DR BindingDB; P35503; -.
DR ChEMBL; CHEMBL3542435; -.
DR DrugBank; DB06403; Ambrisentan.
DR DrugBank; DB01217; Anastrozole.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB13997; Baloxavir marboxil.
DR DrugBank; DB13919; Candesartan.
DR DrugBank; DB00796; Candesartan cilexetil.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB00434; Cyproheptadine.
DR DrugBank; DB01609; Deferasirox.
DR DrugBank; DB11943; Delafloxacin.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB05928; Dovitinib.
DR DrugBank; DB06210; Eltrombopag.
DR DrugBank; DB09038; Empagliflozin.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB00749; Etodolac.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB04953; Ezogabine.
DR DrugBank; DB04854; Febuxostat.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00712; Flurbiprofen.
DR DrugBank; DB01095; Fluvastatin.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB06741; Gavestinel.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB00327; Hydromorphone.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB01029; Irbesartan.
DR DrugBank; DB00920; Ketotifen.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB04725; Licofelone.
DR DrugBank; DB00455; Loratadine.
DR DrugBank; DB12130; Lorlatinib.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB01252; Mitiglinide.
DR DrugBank; DB00295; Morphine.
DR DrugBank; DB06510; Muraglitazar.
DR DrugBank; DB11691; Naldemedine.
DR DrugBank; DB06230; Nalmefene.
DR DrugBank; DB08804; Nandrolone decanoate.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB08860; Pitavastatin.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB11689; Selumetinib.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB00966; Telmisartan.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB00313; Valproic acid.
DR SwissLipids; SLP:000001698; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1875; 2 N-Linked glycans (1 site).
DR GlyGen; P35503; 4 sites, 2 N-linked glycans (1 site).
DR iPTMnet; P35503; -.
DR PhosphoSitePlus; P35503; -.
DR BioMuta; UGT1A3; -.
DR jPOST; P35503; -.
DR MassIVE; P35503; -.
DR PaxDb; P35503; -.
DR PeptideAtlas; P35503; -.
DR PRIDE; P35503; -.
DR ProteomicsDB; 55072; -. [P35503-1]
DR Antibodypedia; 35062; 15 antibodies from 9 providers.
DR DNASU; 54659; -.
DR Ensembl; ENST00000482026.6; ENSP00000418532.1; ENSG00000288702.1. [P35503-1]
DR GeneID; 54659; -.
DR KEGG; hsa:54659; -.
DR MANE-Select; ENST00000482026.6; ENSP00000418532.1; NM_019093.4; NP_061966.1.
DR UCSC; uc061tvt.1; human. [P35503-1]
DR CTD; 54659; -.
DR DisGeNET; 54659; -.
DR GeneCards; UGT1A3; -.
DR HGNC; HGNC:12535; UGT1A3.
DR HPA; ENSG00000243135; Tissue enriched (liver).
DR MalaCards; UGT1A3; -.
DR MIM; 191740; gene.
DR MIM; 606428; gene.
DR neXtProt; NX_P35503; -.
DR PharmGKB; PA37178; -.
DR VEuPathDB; HostDB:ENSG00000243135; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000162976; -.
DR HOGENOM; CLU_012949_1_3_1; -.
DR InParanoid; P35503; -.
DR OMA; KYFCHIS; -.
DR PhylomeDB; P35503; -.
DR TreeFam; TF315472; -.
DR BioCyc; MetaCyc:HS09519-MON; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; P35503; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9623433; NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR Reactome; R-HSA-9754706; Atorvastatin ADME.
DR SABIO-RK; P35503; -.
DR SignaLink; P35503; -.
DR BioGRID-ORCS; 54659; 5 hits in 921 CRISPR screens.
DR GeneWiki; UGT1A3; -.
DR GenomeRNAi; 54659; -.
DR Pharos; P35503; Tbio.
DR PRO; PR:P35503; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P35503; protein.
DR Genevisible; P35503; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; IDA:BHF-UCL.
DR GO; GO:0032782; P:bile acid secretion; IDA:UniProtKB.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0052696; P:flavonoid glucuronidation; IDA:BHF-UCL.
DR GO; GO:2001030; P:negative regulation of cellular glucuronidation; ISS:BHF-UCL.
DR GO; GO:0045922; P:negative regulation of fatty acid metabolic process; ISS:BHF-UCL.
DR GO; GO:1904224; P:negative regulation of glucuronosyltransferase activity; ISS:BHF-UCL.
DR GO; GO:0042573; P:retinoic acid metabolic process; IC:BHF-UCL.
DR GO; GO:0070640; P:vitamin D3 metabolic process; IDA:UniProtKB.
DR GO; GO:0052697; P:xenobiotic glucuronidation; IDA:BHF-UCL.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR002213; UDP_glucos_trans.
DR InterPro; IPR035595; UDP_glycos_trans_CS.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lipid metabolism; Membrane; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..534
FT /note="UDP-glucuronosyltransferase 1A3"
FT /id="PRO_0000036002"
FT TRANSMEM 492..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 436..534
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053959"
FT VARIANT 6
FT /note="Q -> R (in dbSNP:rs28898617)"
FT /id="VAR_052445"
FT VARIANT 11
FT /note="W -> R (in dbSNP:rs3821242)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_052446"
FT VARIANT 45
FT /note="R -> W (in dbSNP:rs45625338)"
FT /id="VAR_052447"
FT VARIANT 47
FT /note="V -> A (in dbSNP:rs6431625)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_052448"
FT VARIANT 49
FT /note="R -> W (in dbSNP:rs45595237)"
FT /id="VAR_052449"
FT VARIANT 78
FT /note="T -> I (in dbSNP:rs28898618)"
FT /id="VAR_052450"
FT VARIANT 114
FT /note="M -> I (in dbSNP:rs28898619)"
FT /id="VAR_052451"
FT VARIANT 144
FT /note="T -> I (in dbSNP:rs13406898)"
FT /id="VAR_052452"
FT VARIANT 158
FT /note="A -> V (in dbSNP:rs61764030)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_058583"
FT VARIANT 270
FT /note="M -> V (in dbSNP:rs45449995)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_052453"
SQ SEQUENCE 534 AA; 60338 MW; 9C5833652A4D9B3D CRC64;
MATGLQVPLP WLATGLLLLL SVQPWAESGK VLVVPIDGSH WLSMREVLRE LHARGHQAVV
LTPEVNMHIK EENFFTLTTY AISWTQDEFD RHVLGHTQLY FETEHFLKKF FRSMAMLNNM
SLVYHRSCVE LLHNEALIRH LNATSFDVVL TDPVNLCAAV LAKYLSIPTV FFLRNIPCDL
DFKGTQCPNP SSYIPRLLTT NSDHMTFMQR VKNMLYPLAL SYICHAFSAP YASLASELFQ
REVSVVDILS HASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANRKPLSQE FEAYINASGE
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT ILVKWLPQND
LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD NAKRMETKGA GVTLNVLEMT
SEDLENALKA VINDKSYKEN IMRLSSLHKD RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH
DLTWYQYHSL DVIGFLLAVV LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH
