UD110_HUMAN
ID UD110_HUMAN Reviewed; 530 AA.
AC Q9HAW8; O00474; Q6NT91; Q7Z6H8;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=UDP-glucuronosyltransferase 1A10 {ECO:0000303|PubMed:15472229};
DE Short=UGT1A10;
DE EC=2.4.1.17 {ECO:0000269|PubMed:18052087, ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19545173, ECO:0000269|PubMed:20610558, ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:26220143};
DE AltName: Full=UDP-glucuronosyltransferase 1-10;
DE Short=UDPGT 1-10;
DE Short=UGT1*10;
DE Short=UGT1-10;
DE Short=UGT1.10;
DE AltName: Full=UDP-glucuronosyltransferase 1-J;
DE Short=UGT-1J;
DE Short=UGT1J;
DE Flags: Precursor;
GN Name=UGT1A10 {ECO:0000312|HGNC:HGNC:12531}; 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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9271343; DOI=10.1124/mol.52.2.212;
RA Strassburg C.P., Oldhafer K., Manns M.P., Tukey R.H.;
RT "Differential expression of the UGT1A locus in human liver, biliary, and
RT gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in
RT extrahepatic tissue.";
RL Mol. Pharmacol. 52:212-220(1997).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=12181437; DOI=10.1124/mol.62.3.608;
RA Gagne J.F., Montminy V., Belanger P., Journault K., Gaucher G.,
RA Guillemette C.;
RT "Common human UGT1A polymorphisms and the altered metabolism of irinotecan
RT active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38).";
RL Mol. Pharmacol. 62:608-617(2002).
RN [6]
RP BIOPHYSICOCHEMICAL PROPERTIES.
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 [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), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=18052087; DOI=10.1021/mp700135a;
RA Joseph T.B., Wang S.W., Liu X., Kulkarni K.H., Wang J., Xu H., Hu M.;
RT "Disposition of flavonoids via enteric recycling: enzyme stability affects
RT characterization of prunetin glucuronidation across species, organs, and
RT UGT isoforms.";
RL Mol. Pharm. 4:883-894(2007).
RN [9]
RP FUNCTION (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, AND TISSUE 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 [10]
RP FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY.
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 [11]
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 [12]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=19545173; DOI=10.1021/mp8002557;
RA Tang L., Singh R., Liu Z., Hu M.;
RT "Structure and concentration changes affect characterization of UGT
RT isoform-specific metabolism of isoflavones.";
RL Mol. Pharm. 6:1466-1482(2009).
RN [13]
RP FUNCTION (ISOFORMS 1 AND 2), CATALYTIC ACTIVITY, 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 [14]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF PHE-90 AND PHE-93.
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 [15]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF PHE-93.
RX PubMed=26220143; DOI=10.1016/j.jsbmb.2015.07.013;
RA Kallionpaeae R.A., Jaervinen E., Finel M.;
RT "Glucuronidation of estrone and 16alpha-hydroxyestrone by human UGT
RT enzymes: The key roles of UGT1A10 and UGT2B7.";
RL J. Steroid Biochem. Mol. Biol. 154:104-111(2015).
RN [16]
RP VARIANTS ILE-59 AND ILE-202.
RX PubMed=15618702; DOI=10.2133/dmpk.17.488;
RA Saeki M., Ozawa S., Saito Y., Jinno H., Hamaguchi T., Nokihara H.,
RA Shimada Y., Kunitoh H., Yamamoto N., Ohe Y., Yamada Y., Shirao K., Muto M.,
RA Mera K., Goto K., Ohmatsu H., Kubota K., Niho S., Kakinuma R., Minami H.,
RA Ohtsu A., Yoshida T., Saijo N., Sawada J.;
RT "Three novel single nucleotide polymorphisms in UGT1A10.";
RL Drug Metab. Pharmacokinet. 17:488-490(2002).
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:12181437, PubMed:18004212, PubMed:18052087,
CC PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867,
CC PubMed:26220143). Essential for the elimination and detoxification of
CC drugs, xenobiotics and endogenous compounds (PubMed:12181437,
CC PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen
CC hormones such as estradiol, estrone and estriol (PubMed:18719240,
CC PubMed:23288867, PubMed:26220143). Also catalyzes the glucuronidation
CC of the isoflavones genistein, daidzein, glycitein, formononetin,
CC biochanin A and prunetin, which are phytoestrogens with anticancer and
CC cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved
CC in the glucuronidation of the AGTR1 angiotensin receptor antagonist
CC losartan, caderastan and zolarsatan, drugs which can inhibit the effect
CC of angiotensin II (PubMed:18674515). {ECO:0000269|PubMed:12181437,
CC ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:18052087,
CC ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19545173, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:26220143}.
CC -!- FUNCTION: [Isoform 2]: Lacks UGT glucuronidation activity but acts as a
CC negative regulator of isoform 1. {ECO:0000269|PubMed:18004212,
CC 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:18052087, ECO:0000269|PubMed:18674515,
CC ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19545173,
CC ECO:0000269|PubMed:20610558, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:26220143};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:18052087, ECO:0000305|PubMed:18674515,
CC ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:19545173,
CC ECO:0000305|PubMed:20610558, ECO:0000305|PubMed:23288867,
CC ECO:0000305|PubMed:26220143};
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:18719240, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52461;
CC Evidence={ECO:0000305|PubMed:18719240, 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:18719240, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52465;
CC Evidence={ECO:0000305|PubMed:18719240, 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=16alpha,17beta-estriol + UDP-alpha-D-glucuronate =
CC 16alpha,17beta-estriol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52468, ChEBI:CHEBI:15378, ChEBI:CHEBI:27974,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136649;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52469;
CC Evidence={ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16beta,17beta-estriol + UDP-alpha-D-glucuronate =
CC 16beta,17beta-estriol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52876, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:87620, ChEBI:CHEBI:136885;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52877;
CC Evidence={ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16alpha,17alpha-estriol + UDP-alpha-D-glucuronate =
CC 16alpha,17alpha-estriol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52924, ChEBI:CHEBI:15378, ChEBI:CHEBI:42156,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136882;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52925;
CC Evidence={ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16alpha-hydroxyestrone + UDP-alpha-D-glucuronate = 16alpha-
CC hydroxyestrone 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52448, ChEBI:CHEBI:776, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136635;
CC Evidence={ECO:0000269|PubMed:26220143};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52449;
CC Evidence={ECO:0000305|PubMed:26220143};
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:26220143};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52477;
CC Evidence={ECO:0000305|PubMed:26220143};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prunetin + UDP-alpha-D-glucuronate = prunetin-4'-O-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63588, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:147403, ChEBI:CHEBI:147404;
CC Evidence={ECO:0000269|PubMed:18052087};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63589;
CC Evidence={ECO:0000305|PubMed:18052087};
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 O-beta-D-
CC glucuronoside + UDP; Xref=Rhea:RHEA:63724, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149509, ChEBI:CHEBI:149522;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63725;
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-1-N-
CC beta-D-glucuronide; Xref=Rhea:RHEA:63744, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149524, ChEBI:CHEBI:149527;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63745;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:26220143};
CC KM=4.07 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=2.63 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=21.8 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=68.4 uM for 16alpha,17beta-estriol/estriol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:23288867};
CC KM=59.8 uM for 16beta,17beta-estriol (when assaying glucuronidation
CC at position 3) {ECO:0000269|PubMed:23288867};
CC KM=337 uM for 16alpha,17alpha-estriol (when assaying glucuronidation
CC at position 3) {ECO:0000269|PubMed:23288867};
CC KM=12.34 uM for genistein {ECO:0000269|PubMed:19545173};
CC KM=31.5 uM for SN-38 (when assaying glucuronidation at position 10)
CC {ECO:0000269|PubMed:12181437};
CC Vmax=1300 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:26220143};
CC Vmax=6340 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=83.6 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=2100 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=3040 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=107 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=321 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=8.5 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=1200 pmol/min/mg enzyme for the formation of 16alpha,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=837 pmol/min/mg enzyme for the formation of 16alpha,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=7700 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=3486 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=958 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=407 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=3 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=3 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-D-
CC glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=11 pmol/min/mg enzyme for the formation of 2-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1.04 nmol/min/mg enzyme for the formation of genistein
CC glucuronide {ECO:0000269|PubMed:19545173};
CC Vmax=0.25 nmol/min/mg enzyme for the formation of prunetin-4'-O-
CC (beta-D-glucuronoside) {ECO:0000269|PubMed:18052087};
CC Vmax=7.6 pmol/min/mg enzyme for the formation of SN-38 glucuronide
CC {ECO:0000269|PubMed:12181437};
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:12181437, ECO:0000305|PubMed:15472229,
CC ECO:0000305|PubMed:18052087, ECO:0000305|PubMed:19545173};
CC -!- SUBUNIT: Homodimer (PubMed:17179145). Homooligomer (Probable).
CC Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and
CC UGT1A9 to form heterodimers (PubMed:17179145). Isoform 1 interacts with
CC isoform 2/i2 suggesting that oligomerization is involved in negative
CC regulation of transferase activity by isoform 2. Isoform 1 also
CC interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4,
CC UGT1A6, UGT1A7, UGT1A8 and UGT1A9 (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=Q9HAW8-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A10s;
CC IsoId=Q9HAW8-2; Sequence=VSP_053966;
CC -!- TISSUE SPECIFICITY: Liver and colon (PubMed:9271343). Isoform 1 and
CC isoform 2 are expressed in colon, esophagus and small intestine;
CC isoform 2 but not isoform 1 is expressed in liver or kidney
CC (PubMed:18004212). {ECO:0000269|PubMed:18004212,
CC ECO:0000269|PubMed:9271343}.
CC -!- MISCELLANEOUS: UGT1A10 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U89508; AAB81537.1; -; mRNA.
DR EMBL; AF297093; AAG30417.1; -; Genomic_DNA.
DR EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020971; AAH20971.1; -; mRNA.
DR EMBL; BC053576; AAH53576.1; -; mRNA.
DR EMBL; BC069210; AAH69210.2; -; mRNA.
DR CCDS; CCDS33403.1; -. [Q9HAW8-1]
DR PIR; JC5656; JC5656.
DR RefSeq; NP_061948.1; NM_019075.2. [Q9HAW8-1]
DR AlphaFoldDB; Q9HAW8; -.
DR SMR; Q9HAW8; -.
DR BioGRID; 120053; 42.
DR IntAct; Q9HAW8; 20.
DR STRING; 9606.ENSP00000343838; -.
DR BindingDB; Q9HAW8; -.
DR ChEMBL; CHEMBL1743320; -.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB06401; Bazedoxifene.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB00749; Etodolac.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB08804; Nandrolone decanoate.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB00313; Valproic acid.
DR DrugCentral; Q9HAW8; -.
DR SwissLipids; SLP:000001694; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1874; 2 N-Linked glycans (1 site).
DR GlyGen; Q9HAW8; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9HAW8; -.
DR PhosphoSitePlus; Q9HAW8; -.
DR BioMuta; UGT1A10; -.
DR DMDM; 29839636; -.
DR jPOST; Q9HAW8; -.
DR MassIVE; Q9HAW8; -.
DR MaxQB; Q9HAW8; -.
DR PaxDb; Q9HAW8; -.
DR PeptideAtlas; Q9HAW8; -.
DR PRIDE; Q9HAW8; -.
DR ProteomicsDB; 69409; -.
DR ProteomicsDB; 81455; -. [Q9HAW8-1]
DR Antibodypedia; 35063; 35 antibodies from 17 providers.
DR DNASU; 54575; -.
DR Ensembl; ENST00000344644.10; ENSP00000343838.5; ENSG00000242515.6. [Q9HAW8-1]
DR Ensembl; ENST00000373445.1; ENSP00000362544.1; ENSG00000242515.6. [Q9HAW8-2]
DR GeneID; 54575; -.
DR KEGG; hsa:54575; -.
DR MANE-Select; ENST00000344644.10; ENSP00000343838.5; NM_019075.4; NP_061948.1.
DR UCSC; uc002vuq.4; human. [Q9HAW8-1]
DR CTD; 54575; -.
DR DisGeNET; 54575; -.
DR GeneCards; UGT1A10; -.
DR HGNC; HGNC:12531; UGT1A10.
DR HPA; ENSG00000242515; Tissue enhanced (gallbladder, intestine, stomach).
DR MalaCards; UGT1A10; -.
DR MIM; 191740; gene.
DR MIM; 606435; gene.
DR neXtProt; NX_Q9HAW8; -.
DR OpenTargets; ENSG00000242515; -.
DR PharmGKB; PA37174; -.
DR VEuPathDB; HostDB:ENSG00000242515; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000163976; -.
DR HOGENOM; CLU_012949_3_1_1; -.
DR InParanoid; Q9HAW8; -.
DR OMA; AFAPMYE; -.
DR PhylomeDB; Q9HAW8; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; Q9HAW8; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SABIO-RK; Q9HAW8; -.
DR SignaLink; Q9HAW8; -.
DR SIGNOR; Q9HAW8; -.
DR BioGRID-ORCS; 54575; 7 hits in 949 CRISPR screens.
DR GeneWiki; UGT1A10; -.
DR GenomeRNAi; 54575; -.
DR Pharos; Q9HAW8; Tbio.
DR PRO; PR:Q9HAW8; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HAW8; protein.
DR Bgee; ENSG00000242515; Expressed in mucosa of transverse colon and 46 other tissues.
DR ExpressionAtlas; Q9HAW8; baseline and differential.
DR Genevisible; Q9HAW8; 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:BHF-UCL.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IDA:BHF-UCL.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:BHF-UCL.
DR GO; GO:0051552; P:flavone metabolic process; IDA:BHF-UCL.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001889; P:liver development; IBA:GO_Central.
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:0006805; P:xenobiotic metabolic process; TAS:Reactome.
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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..530
FT /note="UDP-glucuronosyltransferase 1A10"
FT /id="PRO_0000036009"
FT TRANSMEM 488..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 432..530
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_053966"
FT VARIANT 59
FT /note="M -> I (in dbSNP:rs56935833)"
FT /evidence="ECO:0000269|PubMed:15618702"
FT /id="VAR_018354"
FT VARIANT 139
FT /note="E -> K (in dbSNP:rs10187694)"
FT /id="VAR_052464"
FT VARIANT 202
FT /note="T -> I (in dbSNP:rs58704432)"
FT /evidence="ECO:0000269|PubMed:15618702"
FT /id="VAR_018355"
FT VARIANT 244
FT /note="L -> I (in dbSNP:rs28969685)"
FT /id="VAR_052465"
FT MUTAGEN 90
FT /note="F->G,A,V,L,I,Y: Loss of estrone and 16alpha-
FT hydroxyestrone glucuronosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23288867"
FT MUTAGEN 93
FT /note="F->G: Increased estriol, 17-epiestriol and 16alpha-
FT hydroxyestrone glucuronosyltransferase activity. Decreased
FT of estrone and 16-epiestriol glucuronosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:23288867,
FT ECO:0000269|PubMed:26220143"
FT MUTAGEN 93
FT /note="F->V,L,I: Loss of estrone and 16alpha-hydroxyestrone
FT glucuronosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23288867"
FT MUTAGEN 93
FT /note="F->Y: Decreased estrone and 16alpha-hydroxyestrone
FT glucuronosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:23288867"
FT CONFLICT 1..23
FT /note="MARAGWTSPVPLCVCLLLTCGFA -> MAPRRVDQPRSFMCVSTADLWLC
FT (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="T -> A (in Ref. 1; AAB81537)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="H -> R (in Ref. 1; AAB81537)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="F -> L (in Ref. 1; AAB81537)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 59810 MW; 73774EEEC7FE37BA CRC64;
MARAGWTSPV PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MQSVVEKLIL RGHEVVVVMP
EVSWQLERSL NCTVKTYSTS YTLEDQNREF MVFAHAQWKA QAQSIFSLLM SSSSGFLDLF
FSHCRSLFND RKLVEYLKES SFDAVFLDPF DTCGLIVAKY FSLPSVVFTR GIFCHHLEEG
AQCPAPLSYV PNDLLGFSDA MTFKERVWNH IVHLEDHLFC QYLFRNALEI ASEILQTPVT
AYDLYSHTSI WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY INASGEHGIV
VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK WLPQNDLLGH
PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR METKGAGVTL NVLEMTSEDL
ENALKAVIND KSYKENIMRL SSLHKDRPVE PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW
YQYHSLDVIG FLLAVVLTVA FITFKCCAYG YRKCLGKKGR VKKAHKSKTH
