UD19_HUMAN
ID UD19_HUMAN Reviewed; 530 AA.
AC O60656; B8K285; P36509; Q9HAX0;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=UDP-glucuronosyltransferase 1A9 {ECO:0000303|PubMed:15472229};
DE Short=UGT1A9;
DE EC=2.4.1.17 {ECO:0000269|PubMed:12181437, ECO:0000269|PubMed:15470161, ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18052087, ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:19545173};
DE AltName: Full=UDP-glucuronosyltransferase 1-9;
DE Short=UDPGT 1-9;
DE Short=UGT1*9;
DE Short=UGT1-09;
DE Short=UGT1.9;
DE AltName: Full=UDP-glucuronosyltransferase 1-I;
DE Short=UGT-1I;
DE Short=UGT1I;
DE AltName: Full=lugP4;
DE Flags: Precursor;
GN Name=UGT1A9 {ECO:0000312|HGNC:HGNC:12541}; 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].
RC TISSUE=Liver;
RX PubMed=1910331; DOI=10.1042/bj2780465;
RA Wooster R., Sutherland L., Ebner T., Clarke D., da Cruz e Silva O.,
RA Burchell B.;
RT "Cloning and stable expression of a new member of the human liver
RT phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.";
RL Biochem. J. 278:465-469(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Ciotti M., Potter C., Owens I.S.;
RT "Human phenol metabolizing UDP-glucuronosyltransferase.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-285.
RA Owens I.S., Gong Q., Cho J.W., Potter C., Gholami N.;
RT "Human phenol UDP-glucuronosyltransferase (UGT1A9) gene isozyme exon 1.";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RA Guillemette C., Levesque E., Girard H., Bernard O.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBSTRATE SPECIFICITY.
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 [9]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP 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 [10]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBSTRATE SPECIFICITY.
RX PubMed=15470161; DOI=10.1124/dmd.104.001651;
RA Picard N., Ratanasavanh D., Premaud A., Le Meur Y., Marquet P.;
RT "Identification of the UDP-glucuronosyltransferase isoforms involved in
RT mycophenolic acid phase II metabolism.";
RL Drug Metab. Dispos. 33:139-146(2005).
RN [11]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16595710; DOI=10.1124/dmd.106.009621;
RA Murai T., Samata N., Iwabuchi H., Ikeda T.;
RT "Human UDP-glucuronosyltransferase, UGT1A8, glucuronidates
RT dihydrotestosterone to a monoglucuronide and further to a structurally
RT novel diglucuronide.";
RL Drug Metab. Dispos. 34:1102-1108(2006).
RN [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP GLYCOSYLATION AT ASN-71; ASN-292 AND ASN-344.
RX PubMed=19951703; DOI=10.1016/j.bcp.2009.11.020;
RA Nakajima M., Koga T., Sakai H., Yamanaka H., Fujiwara R., Yokoi T.;
RT "N-Glycosylation plays a role in protein folding of human UGT1A9.";
RL Biochem. Pharmacol. 79:1165-1172(2010).
RN [19]
RP BIOPHYSICOCHEMICAL PROPERTIES.
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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-442.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [22]
RP VARIANT THR-33.
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:12181437, PubMed:15472229, PubMed:15470161,
CC PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173).
CC Essential for the elimination and detoxification of drugs, xenobiotics
CC and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes
CC the glucuronidation of endogenous estrogen hormones such as estradiol
CC and estrone (PubMed:15472229). Also catalyzes the glucuronidation of
CC the isoflavones genistein, daidzein, glycitein, formononetin, biochanin
CC 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 caderastan, a drug which can inhibit the effect of angiotensin II
CC (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-
CC hydroxycamptothecin (SN-38), the pharmacologically active metabolite of
CC the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also
CC metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161,
CC PubMed:18004212). {ECO:0000269|PubMed:12181437,
CC ECO:0000269|PubMed:15470161, ECO:0000269|PubMed:15472229,
CC ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:18052087,
CC ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:19545173,
CC ECO:0000269|PubMed:20610558}.
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:12181437, ECO:0000269|PubMed:15470161,
CC ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18004212,
CC ECO:0000269|PubMed:18052087, ECO:0000269|PubMed:18674515,
CC ECO:0000269|PubMed:19545173};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:12181437, ECO:0000305|PubMed:15470161,
CC ECO:0000305|PubMed:15472229, ECO:0000305|PubMed:18004212,
CC ECO:0000305|PubMed:18052087, ECO:0000305|PubMed:18674515,
CC ECO:0000305|PubMed:19545173};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-17beta-estradiol + UDP-alpha-D-glucuronate = 2-
CC hydroxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53004, ChEBI:CHEBI:15378, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136931;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53005;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxy-17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-
CC estradiol 4-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53040, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:62845, ChEBI:CHEBI:136937;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53041;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyestrone + UDP-alpha-D-glucuronate = 2-hydroxyestrone
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53048,
CC ChEBI:CHEBI:1156, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136967;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53049;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxyestrone + UDP-alpha-D-glucuronate = estrone 4-O-
CC (beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53060,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:87602, ChEBI:CHEBI:136970;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53061;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prunetin + UDP-alpha-D-glucuronate = prunetin-5-O-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63612, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:147403, ChEBI:CHEBI:147405;
CC Evidence={ECO:0000269|PubMed:18052087};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63613;
CC Evidence={ECO:0000305|PubMed:18052087};
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=SN-38 + UDP-alpha-D-glucuronate = H(+) + SN-38 O-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63696, ChEBI:CHEBI:8988,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:149482; Evidence={ECO:0000269|PubMed:12181437};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63697;
CC Evidence={ECO:0000305|PubMed:12181437};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=mycophenolate + UDP-alpha-D-glucuronate = H(+) + mycophenolate
CC 7-O-beta-D-glucuronide + UDP; Xref=Rhea:RHEA:63704,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:62932, ChEBI:CHEBI:149486;
CC Evidence={ECO:0000269|PubMed:15470161, ECO:0000269|PubMed:18004212};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63705;
CC Evidence={ECO:0000305|PubMed:15470161, ECO:0000305|PubMed:18004212};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:15472229};
CC KM=17 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 2) {ECO:0000269|PubMed:15472229};
CC KM=24 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=43 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 2) {ECO:0000269|PubMed:15472229};
CC KM=58 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=53 uM for 2-methoxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=126 uM for 2-methoxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=55 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=53 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 4) {ECO:0000269|PubMed:15472229};
CC KM=241 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=142 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 4) {ECO:0000269|PubMed:15472229};
CC KM=2.09 uM for genistein {ECO:0000269|PubMed:19545173};
CC KM=0.7 uM for SN-38 (when assaying glucuronidation at position 10)
CC {ECO:0000269|PubMed:12181437};
CC KM=160 uM for mycophenolate (when assaying glucuronidation at
CC position 7) {ECO:0000269|PubMed:15470161};
CC Vmax=4 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-D-
CC glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=6 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 2-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=145 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=11 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 2-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=118 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=7 pmol/min/mg enzyme for the formation of 2-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=41 pmol/min/mg enzyme for the formation of 2-methoxyestrone 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=17 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1673 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 4-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=63 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=524 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone 4-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=5.3 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=3.5 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=1.29 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-5-O-(beta-
CC D-glucuronoside) {ECO:0000269|PubMed:18052087};
CC Vmax=0.012 pmol/min/mg enzyme with 5alpha-dihydrotestosterone 17-O-
CC (beta-D-glucuronate) as substrate, for the formation of 5alpha-
CC dihydrotestosterone 17-O-[beta-D-glucuronosyl-(1->2)-glucuronate]
CC {ECO:0000269|PubMed:16595710};
CC Vmax=2.4 pmol/min/mg enzyme for the formation of SN-38 glucuronide
CC {ECO:0000269|PubMed:12181437};
CC Vmax=11.82 nmol/min/mg enzyme for the formation of mycophenolate 7-O-
CC glucuronide {ECO:0000269|PubMed:15470161};
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:15470161, ECO:0000305|PubMed:16595710,
CC ECO:0000305|PubMed:18052087};
CC -!- SUBUNIT: Homodimer (PubMed:17179145). Homooligomer (Probable).
CC Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 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, UGT1A3, UGT1A4,
CC UGT1A6, UGT1A7, UGT1A8 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=O60656-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A9s;
CC IsoId=O60656-2; Sequence=VSP_053965;
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, colon,
CC esophagus and small intestine. {ECO:0000269|PubMed:18004212}.
CC -!- MISCELLANEOUS: UGT1A9 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 -!- SEQUENCE CAUTION:
CC Sequence=AAB19791.2; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; S55985; AAB19791.2; ALT_FRAME; mRNA.
DR EMBL; AF056188; AAC31425.1; -; mRNA.
DR EMBL; AF297093; AAG30418.1; -; Genomic_DNA.
DR EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058844; AAH58844.1; -; mRNA.
DR EMBL; AF297091; AAG29816.1; -; Genomic_DNA.
DR EMBL; DQ364246; ABC96770.1; -; mRNA.
DR CCDS; CCDS2505.1; -. [O60656-1]
DR PIR; S17512; S17512.
DR RefSeq; NP_066307.1; NM_021027.2. [O60656-1]
DR AlphaFoldDB; O60656; -.
DR SMR; O60656; -.
DR BioGRID; 120073; 15.
DR IntAct; O60656; 9.
DR STRING; 9606.ENSP00000346768; -.
DR BindingDB; O60656; -.
DR ChEMBL; CHEMBL1743319; -.
DR DrugBank; DB00316; Acetaminophen.
DR DrugBank; DB06403; Ambrisentan.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB09274; Artesunate.
DR DrugBank; DB05016; Ataluren.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB11751; Cabotegravir.
DR DrugBank; DB08907; Canagliflozin.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB06695; Dabigatran etexilate.
DR DrugBank; DB06292; Dapagliflozin.
DR DrugBank; DB12941; Darolutamide.
DR DrugBank; DB01609; Deferasirox.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB00586; Diclofenac.
DR DrugBank; DB00861; Diflunisal.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB06210; Eltrombopag.
DR DrugBank; DB09038; Empagliflozin.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB00494; Entacapone.
DR DrugBank; DB11827; Ertugliflozin.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB00749; Etodolac.
DR DrugBank; DB04953; Ezogabine.
DR DrugBank; DB04854; Febuxostat.
DR DrugBank; DB01039; Fenofibrate.
DR DrugBank; DB00712; Flurbiprofen.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB01320; Fosphenytoin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB06741; Gavestinel.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB11978; Glasdegib.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB06738; Ketobemidone.
DR DrugBank; DB00598; Labetalol.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB01283; Lumiracoxib.
DR DrugBank; DB00784; Mefenamic acid.
DR DrugBank; DB09241; Methylene blue.
DR DrugBank; DB09285; Morniflumate.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB01024; Mycophenolic acid.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB00731; Nateglinide.
DR DrugBank; DB04552; Niflumic acid.
DR DrugBank; DB00842; Oxazepam.
DR DrugBank; DB00935; Oxymetazoline.
DR DrugBank; DB04824; Phenolphthalein.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB06739; Seratrodast.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB06204; Tapentadol.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB01685; Topiroxostat.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB13609; Umifenovir.
DR DrugBank; DB06235; Vadimezan.
DR DrugBank; DB00580; Valdecoxib.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB15456; Vericiguat.
DR DrugBank; DB00744; Zileuton.
DR DrugCentral; O60656; -.
DR SwissLipids; SLP:000001713; -. [O60656-1]
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1881; 2 N-Linked glycans (1 site).
DR GlyGen; O60656; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; O60656; -.
DR PhosphoSitePlus; O60656; -.
DR BioMuta; UGT1A9; -.
DR jPOST; O60656; -.
DR MassIVE; O60656; -.
DR PaxDb; O60656; -.
DR PeptideAtlas; O60656; -.
DR PRIDE; O60656; -.
DR ProteomicsDB; 49498; -. [O60656-1]
DR Antibodypedia; 35060; 243 antibodies from 27 providers.
DR DNASU; 54600; -.
DR Ensembl; ENST00000354728.5; ENSP00000346768.4; ENSG00000241119.2. [O60656-1]
DR GeneID; 54600; -.
DR KEGG; hsa:54600; -.
DR MANE-Select; ENST00000354728.5; ENSP00000346768.4; NM_021027.3; NP_066307.1.
DR CTD; 54600; -.
DR DisGeNET; 54600; -.
DR GeneCards; UGT1A9; -.
DR HGNC; HGNC:12541; UGT1A9.
DR HPA; ENSG00000241119; Group enriched (kidney, liver).
DR MalaCards; UGT1A9; -.
DR MIM; 191740; gene.
DR MIM; 606434; gene.
DR neXtProt; NX_O60656; -.
DR OpenTargets; ENSG00000241119; -.
DR PharmGKB; PA419; -.
DR VEuPathDB; HostDB:ENSG00000241119; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000163976; -.
DR HOGENOM; CLU_012949_3_1_1; -.
DR InParanoid; O60656; -.
DR OMA; WVLRNAN; -.
DR PhylomeDB; O60656; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; O60656; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SABIO-RK; O60656; -.
DR SignaLink; O60656; -.
DR SIGNOR; O60656; -.
DR BioGRID-ORCS; 54600; 24 hits in 960 CRISPR screens.
DR GeneWiki; UGT1A9; -.
DR GenomeRNAi; 54600; -.
DR Pharos; O60656; Tbio.
DR PRO; PR:O60656; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O60656; protein.
DR Bgee; ENSG00000241119; Expressed in adult mammalian kidney and 32 other tissues.
DR ExpressionAtlas; O60656; baseline and differential.
DR Genevisible; O60656; 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:0004857; F:enzyme inhibitor activity; IGI: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:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0051552; P:flavone metabolic process; IDA:BHF-UCL.
DR GO; GO:0052696; P:flavonoid glucuronidation; IDA:BHF-UCL.
DR GO; GO:0001889; P:liver development; IBA:GO_Central.
DR GO; GO:2001030; P:negative regulation of cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0045922; P:negative regulation of fatty acid metabolic process; IDA:BHF-UCL.
DR GO; GO:1904224; P:negative regulation of glucuronosyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0042573; P:retinoic acid metabolic process; IC:BHF-UCL.
DR GO; GO:0052697; P:xenobiotic glucuronidation; IDA:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
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 1A9"
FT /id="PRO_0000036008"
FT TRANSMEM 488..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 99
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q62452"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19951703"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19951703"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19951703"
FT VAR_SEQ 432..530
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053965"
FT VARIANT 33
FT /note="M -> T (in dbSNP:rs72551330)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_058587"
FT VARIANT 442
FT /note="S -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036035"
FT CONFLICT 29
FT /note="L -> V (in Ref. 1; AAB19791)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="A -> D (in Ref. 1; AAB19791)"
FT /evidence="ECO:0000305"
FT CONFLICT 279..282
FT /note="QGKP -> ERKA (in Ref. 1; AAB19791)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 59941 MW; C417B9E86B403078 CRC64;
MACTGWTSPL PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MRSVVEKLIL RGHEVVVVMP
EVSWQLGRSL NCTVKTYSTS YTLEDLDREF KAFAHAQWKA QVRSIYSLLM GSYNDIFDLF
FSNCRSLFKD KKLVEYLKES SFDAVFLDPF DNCGLIVAKY FSLPSVVFAR GILCHYLEEG
AQCPAPLSYV PRILLGFSDA MTFKERVRNH IMHLEEHLLC HRFFKNALEI ASEILQTPVT
EYDLYSHTSI 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
