UD18_HUMAN
ID UD18_HUMAN Reviewed; 530 AA.
AC Q9HAW9; B2R8S3; B8K290; O14928; Q8TEX4; Q8WTQ9; Q8WX85;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=UDP-glucuronosyltransferase 1A8 {ECO:0000303|PubMed:15472229, ECO:0000303|PubMed:18719240};
DE Short=UGT1A8;
DE EC=2.4.1.17 {ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:16595710, ECO:0000269|PubMed:18052087, ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:20610558, ECO:0000269|PubMed:23288867};
DE AltName: Full=UDP-glucuronosyltransferase 1-8;
DE Short=UDPGT 1-8;
DE Short=UGT1*8;
DE Short=UGT1-08;
DE Short=UGT1.8;
DE AltName: Full=UDP-glucuronosyltransferase 1-H;
DE Short=UGT-1H;
DE Short=UGT1H;
DE Flags: Precursor;
GN Name=UGT1A8 {ECO:0000312|HGNC:HGNC:12540}; 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), TISSUE SPECIFICITY, AND VARIANTS
RP ARG-132; ALA-154; GLY-173; ALA-202 AND LEU-212.
RX PubMed=9535849; DOI=10.1074/jbc.273.15.8719;
RA Strassburg C.P., Manns M.P., Tukey R.H.;
RT "Expression of the UDP-glucuronosyltransferase 1A locus in human colon.
RT Identification and characterization of the novel extrahepatic UGT1A8.";
RL J. Biol. Chem. 273:8719-8726(1998).
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 [MRNA] (ISOFORM 1), AND VARIANTS GLY-173 AND TYR-277.
RC TISSUE=Colon;
RX PubMed=12042666; DOI=10.1097/00008571-200206000-00004;
RA Huang Y.-H., Galijatovic A., Nguyen N., Geske D., Beaton D., Green J.,
RA Green M., Peters W.H., Tukey R.H.;
RT "Identification and functional characterization of UDP-
RT glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3.";
RL Pharmacogenetics 12:287-297(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-173.
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-285, AND VARIANTS ARG-132; ALA-154;
RP GLY-173; ALA-202 AND LEU-212.
RA Strassburg C.P., Vogel A., Manns M.P.;
RT "Identification of genetic polymorphisms within the human extrahepatic
RT UGT1A8 gene.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP BIOPHYSICOCHEMICAL 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 [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 BIOPHYSICOCHEMICAL PROPERTIES.
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 FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBSTRATE SPECIFICITY.
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), ALTERNATIVE SPLICING, CATALYTIC ACTIVITY, 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, 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 [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-292 AND ASN-344.
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 [18]
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 [19]
RP FUNCTION (ISOFORM 2), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP 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 [20]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP 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 [21]
RP VARIANTS VAL-144; GLY-173; THR-231 AND TYR-277.
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:16595710, PubMed:18052087,
CC PubMed:18004212, PubMed:18674515, PubMed:18719240, PubMed:19545173,
CC PubMed:23288867). Essential for the elimination and detoxification of
CC drugs, xenobiotics and endogenous compounds (PubMed:15472229,
CC PubMed:16595710, PubMed:23288867). Catalyzes the glucuronidation of
CC endogenous steroid hormones such as androgens and estrogens
CC (PubMed:15472229, PubMed:16595710, PubMed:18719240, PubMed:23288867).
CC Produces dihydrotestosterone (DHT) diglucuronide from the DHT after two
CC subsequent glucoronidation steps (PubMed:16595710). Also catalyzes the
CC glucuronidation of the isoflavones genistein, daidzein, glycitein,
CC formononetin, biochanin A and prunetin, which are phytoestrogens with
CC anticancer and cardiovascular properties (PubMed:18052087,
CC PubMed:19545173). Involved in the glucuronidation of the AGTR1
CC angiotensin receptor antagonist caderastan, a drug which can inhibit
CC the effect of angiotensin II (PubMed:18674515). Also metabolizes
CC mycophenolate, an immunosuppressive agent (PubMed:15470161,
CC PubMed:18004212). {ECO:0000269|PubMed:15470161,
CC ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:16595710,
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 -!- 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:15472229, ECO:0000269|PubMed:16595710,
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:20610558,
CC ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:15472229, ECO:0000305|PubMed:16595710,
CC ECO:0000305|PubMed:18004212, ECO:0000305|PubMed:18052087,
CC ECO:0000305|PubMed:18674515, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:19545173, ECO:0000305|PubMed:20610558,
CC ECO:0000305|PubMed:23288867};
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=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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000305|PubMed:18719240};
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=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=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=2-hydroxy-17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-
CC estradiol 2-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53032, ChEBI:CHEBI:15378, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136933;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53033;
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-hydroxy-17beta-estradiol + UDP-alpha-D-glucuronate = 4-
CC hydroxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53036, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:62845, ChEBI:CHEBI:136936;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53037;
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=4-hydroxyestrone + UDP-alpha-D-glucuronate = 4-hydroxyestrone
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53052,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:87602, ChEBI:CHEBI:136969;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53053;
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=2-methoxy-17beta-estradiol + UDP-alpha-D-glucuronate = 2-
CC methoxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53072, ChEBI:CHEBI:15378, ChEBI:CHEBI:28955,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136974;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53073;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methoxyestrone + UDP-alpha-D-glucuronate = 2-methoxyestrone
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53064,
CC ChEBI:CHEBI:1189, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136971;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53065;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methoxy-17beta-estradiol + UDP-alpha-D-glucuronate = 4-
CC methoxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53080, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136975, ChEBI:CHEBI:136976;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53081;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-methoxyestrone + UDP-alpha-D-glucuronate = 4-methoxyestrone
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53068,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136972, ChEBI:CHEBI:136973;
CC Evidence={ECO:0000269|PubMed:15472229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53069;
CC Evidence={ECO:0000305|PubMed:15472229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + UDP-alpha-D-
CC glucuronate = 5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) +
CC H(+) + UDP; Xref=Rhea:RHEA:53000, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16330, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136914; Evidence={ECO:0000269|PubMed:16595710};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53001;
CC Evidence={ECO:0000305|PubMed:16595710};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) + UDP-
CC alpha-D-glucuronate = 5alpha-dihydrotestosterone 17-O-[beta-D-
CC glucuronosyl-(1->2)-glucuronate] + H(+) + UDP; Xref=Rhea:RHEA:53388,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136914, ChEBI:CHEBI:136916;
CC Evidence={ECO:0000269|PubMed:16595710};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53389;
CC Evidence={ECO:0000305|PubMed:16595710};
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=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=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 ECO:0000269|PubMed:20610558};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63705;
CC Evidence={ECO:0000305|PubMed:15470161, ECO:0000305|PubMed:18004212,
CC ECO:0000305|PubMed:20610558};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=61.7 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=10 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=38 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=55 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:15472229};
CC KM=20 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=102 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 2) {ECO:0000269|PubMed:15472229};
CC KM=40 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=52 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 2) {ECO:0000269|PubMed:15472229};
CC KM=118 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=105 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 4) {ECO:0000269|PubMed:15472229};
CC KM=184 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=431 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 4) {ECO:0000269|PubMed:15472229};
CC KM=66 uM for 2-methoxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=69 uM for 2-methoxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=8 uM for 4-methoxy-17beta-estradiol(when assaying glucuronidation
CC at position 3) {ECO:0000269|PubMed:15472229};
CC KM=111 uM for 4-methoxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=1.25 uM for genistein {ECO:0000269|PubMed:19545173};
CC KM=382.3 uM for 17beta-hydroxy-5alpha-androstan-3-one (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:16595710};
CC KM=1390 uM for mycophenolate (when assaying glucuronidation at
CC position 7) {ECO:0000269|PubMed:15470161};
CC KM=20.3 uM for SN-38 (when assaying glucuronidation at position 10)
CC {ECO:0000269|PubMed:12181437};
CC KM=128 uM for mycophenolate (when assaying glucuronidation at
CC position 7) {ECO:0000269|PubMed:20610558};
CC Vmax=200 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=217 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=4.75 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=195 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=142 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-D-
CC glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=188 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=126 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 2-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=88 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=38 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone2-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=119 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=4723 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 4-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1975 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone
CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1538 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone
CC 4-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=1050 pmol/min/mg enzyme for the formation of 2-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=749 pmol/min/mg enzyme for the formation of 2-methoxyestrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=218 pmol/min/mg enzyme for the formation of 4-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=275 pmol/min/mg enzyme for the formation of 4-methoxyestrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=3.3 pmol/min/mg enzyme for the formation of 16alpha,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=16.3 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=78.6 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=47.9 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=15.6 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=0.24 nmol/min/mg enzyme for the formation of prunetin-5-O-(beta-
CC D-glucuronoside) {ECO:0000269|PubMed:18052087};
CC Vmax=0.11 nmol/min/mg enzyme for the formation of prunetin-4'-O-
CC (beta-D-glucuronoside) {ECO:0000269|PubMed:18052087};
CC Vmax=2.24 nmol/min/mg enzyme for the formation of genistein
CC glucuronide {ECO:0000269|PubMed:19545173};
CC Vmax=0.047 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=0.107 pmol/min/mg enzyme with 17beta-hydroxy-5alpha-androstan-3-
CC one as substrate, for the formation of 5alpha-dihydrotestosterone 17-
CC O-[beta-D-glucuronosyl-(1->2)-glucuronate]
CC {ECO:0000269|PubMed:16595710};
CC Vmax=1.9 nmol/min/mg enzyme for the formation of mycophenolate 7-O-
CC glucuronide {ECO:0000269|PubMed:20610558};
CC Vmax=7.27 nmol/min/mg enzyme for the formation of mycophenolate 7-O-
CC glucuronide {ECO:0000269|PubMed:15470161};
CC Vmax=5 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:15470161, ECO:0000305|PubMed:16595710,
CC ECO:0000305|PubMed:18052087, ECO:0000305|PubMed:19545173};
CC -!- SUBUNIT: Homodimer (PubMed:17179145). Homooligomer (Probable).
CC Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, 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, UGT1A3, UGT1A4,
CC UGT1A6, UGT1A7, 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=Q9HAW9-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A8s;
CC IsoId=Q9HAW9-2; Sequence=VSP_053964;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in kidney, colon and small
CC intestine (PubMed:18004212). Not expressed in liver (PubMed:18004212).
CC {ECO:0000269|PubMed:18004212}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver, kidney, colon and
CC small intestine. {ECO:0000269|PubMed:18004212}.
CC -!- MISCELLANEOUS: UGT1A8 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; AF030310; AAB84259.1; -; mRNA.
DR EMBL; AF297093; AAG30416.1; -; Genomic_DNA.
DR EMBL; AF462267; AAL75963.1; -; mRNA.
DR EMBL; AF462268; AAL75964.1; -; mRNA.
DR EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC019072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK313488; BAG36270.1; -; mRNA.
DR EMBL; AF465198; AAL73506.1; -; Genomic_DNA.
DR EMBL; AF465199; AAL73507.1; -; Genomic_DNA.
DR EMBL; AF465200; AAL73508.1; -; Genomic_DNA.
DR EMBL; DQ364251; ABC96775.1; -; mRNA.
DR CCDS; CCDS33402.1; -. [Q9HAW9-1]
DR RefSeq; NP_061949.3; NM_019076.4. [Q9HAW9-1]
DR AlphaFoldDB; Q9HAW9; -.
DR SMR; Q9HAW9; -.
DR BioGRID; 120054; 155.
DR IntAct; Q9HAW9; 7.
DR STRING; 9606.ENSP00000362549; -.
DR BindingDB; Q9HAW9; -.
DR ChEMBL; CHEMBL1743318; -.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB06401; Bazedoxifene.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB00861; Diflunisal.
DR DrugBank; DB09038; Empagliflozin.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB00295; Morphine.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB06230; Nalmefene.
DR DrugBank; DB00788; Naproxen.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB00313; Valproic acid.
DR SwissLipids; SLP:000001710; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1880; 2 N-Linked glycans (1 site).
DR GlyGen; Q9HAW9; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q9HAW9; -.
DR PhosphoSitePlus; Q9HAW9; -.
DR BioMuta; UGT1A8; -.
DR DMDM; 29839637; -.
DR jPOST; Q9HAW9; -.
DR MassIVE; Q9HAW9; -.
DR MaxQB; Q9HAW9; -.
DR PaxDb; Q9HAW9; -.
DR PeptideAtlas; Q9HAW9; -.
DR PRIDE; Q9HAW9; -.
DR ProteomicsDB; 81456; -. [Q9HAW9-1]
DR Antibodypedia; 66865; 5 antibodies from 4 providers.
DR DNASU; 54576; -.
DR Ensembl; ENST00000373450.5; ENSP00000362549.4; ENSG00000242366.4. [Q9HAW9-1]
DR GeneID; 54576; -.
DR KEGG; hsa:54576; -.
DR MANE-Select; ENST00000373450.5; ENSP00000362549.4; NM_019076.5; NP_061949.3.
DR UCSC; uc002vup.4; human. [Q9HAW9-1]
DR CTD; 54576; -.
DR DisGeNET; 54576; -.
DR GeneCards; UGT1A8; -.
DR HGNC; HGNC:12540; UGT1A8.
DR HPA; ENSG00000242366; Tissue enhanced (intestine, liver, urinary bladder).
DR MalaCards; UGT1A8; -.
DR MIM; 191740; gene.
DR MIM; 606433; gene.
DR neXtProt; NX_Q9HAW9; -.
DR OpenTargets; ENSG00000242366; -.
DR PharmGKB; PA37183; -.
DR VEuPathDB; HostDB:ENSG00000242366; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000163976; -.
DR HOGENOM; CLU_012949_0_2_1; -.
DR InParanoid; Q9HAW9; -.
DR OMA; CHYLEDA; -.
DR PhylomeDB; Q9HAW9; -.
DR TreeFam; TF315472; -.
DR BioCyc; MetaCyc:HS10706-MON; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; Q9HAW9; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SABIO-RK; Q9HAW9; -.
DR SignaLink; Q9HAW9; -.
DR SIGNOR; Q9HAW9; -.
DR BioGRID-ORCS; 54576; 23 hits in 948 CRISPR screens.
DR ChiTaRS; UGT1A8; human.
DR GeneWiki; UGT1A8; -.
DR GenomeRNAi; 54576; -.
DR Pharos; Q9HAW9; Tbio.
DR PRO; PR:Q9HAW9; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HAW9; protein.
DR Bgee; ENSG00000242366; Expressed in mucosa of transverse colon and 30 other tissues.
DR ExpressionAtlas; Q9HAW9; baseline and differential.
DR Genevisible; Q9HAW9; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0005504; F:fatty acid binding; IDA: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:0001972; F:retinoic acid binding; IC:BHF-UCL.
DR GO; GO:0005496; F:steroid binding; IDA:BHF-UCL.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:BHF-UCL.
DR GO; GO:0009804; P:coumarin metabolic process; IC:BHF-UCL.
DR GO; GO:0006631; P:fatty acid metabolic process; IDA:BHF-UCL.
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:0045939; P:negative regulation of steroid metabolic process; IC:BHF-UCL.
DR GO; GO:0042573; P:retinoic acid metabolic process; IC:BHF-UCL.
DR GO; GO:0008202; P:steroid metabolic process; IDA:UniProtKB.
DR GO; GO:0052697; P:xenobiotic glucuronidation; IDA:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; 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..25
FT /evidence="ECO:0000255"
FT CHAIN 26..530
FT /note="UDP-glucuronosyltransferase 1A8"
FT /id="PRO_0000036007"
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:0000269|PubMed:19159218"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 432..530
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053964"
FT VARIANT 53
FT /note="H -> N (in dbSNP:rs45504099)"
FT /id="VAR_052463"
FT VARIANT 132
FT /note="K -> R"
FT /evidence="ECO:0000269|PubMed:9535849, ECO:0000269|Ref.6"
FT /id="VAR_015543"
FT VARIANT 144
FT /note="A -> V (in dbSNP:rs17862841)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_058585"
FT VARIANT 154
FT /note="G -> A"
FT /evidence="ECO:0000269|PubMed:9535849, ECO:0000269|Ref.6"
FT /id="VAR_015544"
FT VARIANT 173
FT /note="A -> G (in allele UGT1A8*2; dbSNP:rs1042597)"
FT /evidence="ECO:0000269|PubMed:12042666,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:19204906,
FT ECO:0000269|PubMed:9535849, ECO:0000269|Ref.6"
FT /id="VAR_015545"
FT VARIANT 173
FT /note="A -> V (in dbSNP:rs1042597)"
FT /id="VAR_061871"
FT VARIANT 202
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:9535849, ECO:0000269|Ref.6"
FT /id="VAR_015546"
FT VARIANT 212
FT /note="M -> L (in dbSNP:rs1126803)"
FT /evidence="ECO:0000269|PubMed:9535849, ECO:0000269|Ref.6"
FT /id="VAR_015547"
FT VARIANT 231
FT /note="A -> T (in dbSNP:rs72551325)"
FT /evidence="ECO:0000269|PubMed:19204906"
FT /id="VAR_058586"
FT VARIANT 277
FT /note="C -> Y (in allele UGT1A8*3; dramatic reduction in
FT catalytic activity; dbSNP:rs17863762)"
FT /evidence="ECO:0000269|PubMed:12042666,
FT ECO:0000269|PubMed:19204906"
FT /id="VAR_015549"
SQ SEQUENCE 530 AA; 59742 MW; AD838436940F4190 CRC64;
MARTGWTSPI PLCVSLLLTC GFAEAGKLLV VPMDGSHWFT MQSVVEKLIL RGHEVVVVMP
EVSWQLGKSL NCTVKTYSTS YTLEDLDREF MDFADAQWKA QVRSLFSLFL SSSNGFFNLF
FSHCRSLFND RKLVEYLKES SFDAVFLDPF DACGLIVAKY FSLPSVVFAR GIACHYLEEG
AQCPAPLSYV PRILLGFSDA MTFKERVRNH IMHLEEHLFC QYFSKNALEI 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
