UD11_HUMAN
ID UD11_HUMAN Reviewed; 533 AA.
AC P22309; A6NJC3; B8K286;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=UDP-glucuronosyltransferase 1A1 {ECO:0000303|PubMed:15472229, ECO:0000303|PubMed:18719240};
DE Short=UGT1A1;
DE EC=2.4.1.17 {ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:18004206, ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:23288867};
DE AltName: Full=Bilirubin-specific UDPGT isozyme 1;
DE Short=hUG-BR1;
DE AltName: Full=UDP-glucuronosyltransferase 1-1;
DE Short=UDPGT 1-1;
DE Short=UGT1*1;
DE Short=UGT1-01;
DE Short=UGT1.1;
DE AltName: Full=UDP-glucuronosyltransferase 1A isoform 1;
DE Flags: Precursor;
GN Name=UGT1A1 {ECO:0000312|HGNC:HGNC:12530}; 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).
RC TISSUE=Liver;
RX PubMed=1898728; DOI=10.1016/s0021-9258(17)35280-8;
RA Ritter J.K., Crawford J.M., Owens I.S.;
RT "Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs
RT with expression in COS-1 cells.";
RL J. Biol. Chem. 266:1043-1047(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=1339448; DOI=10.1016/s0021-9258(19)50724-4;
RA Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T.,
RA Owens I.S.;
RT "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-
RT glucuronosyltransferase isozymes with identical carboxyl termini.";
RL J. Biol. Chem. 267:3257-3261(1992).
RN [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 [MRNA] (ISOFORM 2).
RA Guillemette C., Levesque E., Girard H., Bernard O.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP 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 1-50.
RA Ueyama H., Koiwai O., Soeda Y., Sato H., Satoh Y., Ohkubo I., Doida Y.;
RT "Analysis of the promoter of human bilirubin UDP-glucuronosyltransferase
RT gene (UGT1*1) in relevance to Gilbert's syndrome.";
RL Hepatol. Res. 9:152-163(1997).
RN [7]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF GLY-71; PRO-229; LEU-233 AND
RP TYR-486.
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 [8]
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 [9]
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 [10]
RP FUNCTION (ISOFORM 1), AND 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 [11]
RP INVOLVEMENT IN GILBS.
RX PubMed=17496722; DOI=10.1097/fpc.0b013e328012d0da;
RA Hsieh T.Y., Shiu T.Y., Huang S.M., Lin H.H., Lee T.C., Chen P.J., Chu H.C.,
RA Chang W.K., Jeng K.S., Lai M.M., Chao Y.C.;
RT "Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding
RT protein binding affinity of UGT1A1 gene promoter.";
RL Pharmacogenet. Genomics 17:229-236(2007).
RN [12]
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 [13]
RP ALTERNATIVE SPLICING, FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION, SUBUNIT,
RP AND TISSUE SPECIFICITY.
RX PubMed=17187418; DOI=10.1002/hep.21464;
RA Levesque E., Girard H., Journault K., Lepine J., Guillemette C.;
RT "Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new
RT splicing event at the UGT1A locus.";
RL Hepatology 45:128-138(2007).
RN [14]
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 [15]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, KINETIC PARAMETERS, SUBSTRATE
RP SPECIFICITY, AND CHARACTERIZATION OF VARIANTS CN2 ARG-71; LEU-83; GLN-229
RP AND ASP-486.
RX PubMed=18004206; DOI=10.1097/fpc.0b013e328256b1b6;
RA Udomuksorn W., Elliot D.J., Lewis B.C., Mackenzie P.I., Yoovathaworn K.,
RA Miners J.O.;
RT "Influence of mutations associated with Gilbert and Crigler-Najjar type II
RT syndromes on the glucuronidation kinetics of bilirubin and other UDP-
RT glucuronosyltransferase 1A substrates.";
RL Pharmacogenet. Genomics 17:1017-1029(2007).
RN [16]
RP FUNCTION (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, CATALYTIC ACTIVITY, AND
RP 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 [17]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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 [18]
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 [19]
RP FUNCTION (ISOFORM 1).
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 [20]
RP INVOLVEMENT IN BILIQTL1.
RX PubMed=19414484; DOI=10.1093/hmg/ddp202;
RA Johnson A.D., Kavousi M., Smith A.V., Chen M.H., Dehghan A., Aspelund T.,
RA Lin J.P., van Duijn C.M., Harris T.B., Cupples L.A., Uitterlinden A.G.,
RA Launer L., Hofman A., Rivadeneira F., Stricker B., Yang Q., O'Donnell C.J.,
RA Gudnason V., Witteman J.C.;
RT "Genome-wide association meta-analysis for total serum bilirubin levels.";
RL Hum. Mol. Genet. 18:2700-2710(2009).
RN [21]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-102.
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 [22]
RP FUNCTION (ISOFORMS 1 AND 2), AND SUBUNITS.
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 [23]
RP FUNCTION (ISOFORM 1), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND SUBSTRATE SPECIFICITY.
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 [24]
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 [25]
RP VARIANT CN1 PHE-375.
RX PubMed=1634050; DOI=10.1096/fasebj.6.10.1634050;
RA Bosma P.J., Chowdhury J.R., Huang T.-J., Lahiri P., Elferink R.P.J.O.,
RA van Es H.H.G., Lederstein M., Whitington P.F., Jansen P.L.M.,
RA Chowdhury N.R.;
RT "Mechanisms of inherited deficiencies of multiple UDP-
RT glucuronosyltransferase isoforms in two patients with Crigler-Najjar
RT syndrome, type I.";
RL FASEB J. 6:2859-2863(1992).
RN [26]
RP VARIANTS CN2 ARG-71 AND ASP-486.
RX PubMed=8280139; DOI=10.1006/bbrc.1993.2610;
RA Aono S., Yamada Y., Keino H., Hanada N., Nakagawa T., Sasaoka Y.,
RA Yazawa T., Sato H., Koiwai O.;
RT "Identification of defect in the genes for bilirubin UDP-glucuronosyl-
RT transferase in a patient with Crigler-Najjar syndrome type II.";
RL Biochem. Biophys. Res. Commun. 197:1239-1244(1993).
RN [27]
RP VARIANT CN2 ARG-331.
RX PubMed=8276413; DOI=10.1006/geno.1993.1451;
RA Moghrabi N., Clarke D.J., Boxer M., Burchell B.;
RT "Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene
RT complex that causes Crigler-Najjar syndrome type 2.";
RL Genomics 18:171-173(1993).
RN [28]
RP VARIANT CN1 PHE-170 DEL.
RX PubMed=8226884; DOI=10.1016/s0021-9258(19)49501-x;
RA Ritter J.K., Yeatman M.T., Kaiser C., Gridelli B., Owens I.S.;
RT "A phenylalanine codon deletion at the UGT1 gene complex locus of a
RT Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-
RT glucuronosyltransferase.";
RL J. Biol. Chem. 268:23573-23579(1993).
RN [29]
RP VARIANTS CN1 VAL-292; GLU-308; ARG-357; THR-368; ARG-381; PRO-401 AND
RP GLU-428.
RX PubMed=7989045; DOI=10.1007/bf00206965;
RA Labrune P., Myara A., Hadchouel M., Ronchi F., Bernard O., Trivin F.,
RA Roy Chowdhury N., Roy Chowdhury J., Munnich A., Odievre M.;
RT "Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14
RT cases.";
RL Hum. Genet. 94:693-697(1994).
RN [30]
RP VARIANTS CN1 GLU-308 AND PHE-375, AND CHARACTERIZATION OF VARIANTS CN1
RP GLU-308 AND PHE-375.
RX PubMed=7906695; DOI=10.1172/jci117008;
RA Erps L.T., Ritter J.K., Hersh J.H., Blossom D., Martin N.C., Owens I.S.;
RT "Identification of two single base substitutions in the UGT1 gene locus
RT which abolish bilirubin uridine diphosphate glucuronosyltransferase
RT activity in vitro.";
RL J. Clin. Invest. 93:564-570(1994).
RN [31]
RP VARIANTS CN1 PHE-170 DEL; ARG-177; ARG-276 AND PHE-375, AND VARIANTS CN2
RP GLN-175 AND TRP-209.
RX PubMed=7989595; DOI=10.1172/jci117604;
RA Seppen J., Bosma P.J., Goldhoorn B.G., Bakker C.T.M., Roy Chowdhury J.,
RA Roy Chowdhury N., Jansen P.L.M., Oude Elferink R.P.J.;
RT "Discrimination between Crigler-Najjar type I and II by expression of
RT mutant bilirubin uridine diphosphate-glucuronosyltransferase.";
RL J. Clin. Invest. 94:2385-2391(1994).
RN [32]
RP VARIANTS GILBS ARG-71; GLN-229 AND GLY-367, AND INVOLVEMENT IN GILBS.
RC TISSUE=Liver, and Peripheral blood leukocyte;
RX PubMed=7715297; DOI=10.1016/s0140-6736(95)90702-5;
RA Aono S., Adachi Y., Uyama E., Yamada Y., Keino H., Nanno T., Koiwai O.,
RA Sato H.;
RT "Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's
RT syndrome.";
RL Lancet 345:958-959(1995).
RN [33]
RP VARIANT CN2 ARG-15, AND CHARACTERIZATION OF VARIANT CN2 ARG-15.
RX PubMed=8706880; DOI=10.1016/0014-5793(96)00677-1;
RA Seppen J., Steenken E., Lindhout D., Bosma P.J., Oude Elferink R.P.J.;
RT "A mutation which disrupts the hydrophobic core of the signal peptide of
RT bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane
RT protein, causes Crigler-Najjar type II.";
RL FEBS Lett. 390:294-298(1996).
RN [34]
RP VARIANT CN2 THR-294, AND CHARACTERIZATION OF VARIANT CN2 THR-294.
RX PubMed=9639672; DOI=10.1016/s0925-4439(98)00030-1;
RA Ciotti M., Chen F., Rubaltelli F.F., Owens I.S.;
RT "Coding defect and a TATA box mutation at the bilirubin UDP-
RT glucuronosyltransferase gene cause Crigler-Najjar type I disease.";
RL Biochim. Biophys. Acta 1407:40-50(1998).
RN [35]
RP VARIANTS CN2 ARG-71; TRP-209; GLN-229 AND ASP-486.
RX PubMed=9621515; DOI=10.1007/s100380050050;
RA Yamamoto K., Soeda Y., Kamisako T., Hosaka H., Fukano M., Sato H.,
RA Fujiyama Y., Dachi Y., Satoh Y., Bamba T.;
RT "Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase
RT gene mutations in seven patients with Crigler-Najjar syndrome type II.";
RL J. Hum. Genet. 43:111-114(1998).
RN [36]
RP VARIANT GILBS ASP-486.
RX PubMed=9627603; DOI=10.1016/s0022-3476(98)70408-1;
RA Maruo Y., Sato H., Yamano T., Doida Y., Shimada M.;
RT "Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of
RT bilirubin UDP-glucuronosyltransferase gene.";
RL J. Pediatr. 132:1045-1047(1998).
RN [37]
RP VARIANTS CN1 ASP-39; PHE-170 DEL; ARG-177; ARG-276; VAL-291; GLU-308;
RP TRP-336; ARG-357; THR-368; PHE-375; ARG-381; SER-387; PRO-401 AND GLU-428,
RP VARIANTS CN2 ARG-15; GLN-175; TRP-209; GLY-225 AND ARG-331, AND VARIANTS
RP GILBS ARG-71; GLN-229; THR-294; GLY-367 AND ASP-486.
RX PubMed=11013440;
RX DOI=10.1002/1098-1004(200010)16:4<297::aid-humu2>3.0.co;2-z;
RA Kadakol A., Ghosh S.S., Sappal B.S., Sharma G., Chowdhury J.R.,
RA Chowdhury N.R.;
RT "Genetic lesions of bilirubin uridine-diphosphoglucuronate
RT glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert
RT syndromes: correlation of genotype to phenotype.";
RL Hum. Mutat. 16:297-306(2000).
RN [38]
RP VARIANTS HBLRTFN ARG-71 AND ASP-486.
RX PubMed=11061796; DOI=10.1542/peds.106.5.e59;
RA Maruo Y., Nishizawa K., Sato H., Sawa H., Shimada M.;
RT "Prolonged unconjugated hyperbilirubinemia associated with breast milk and
RT mutations of the bilirubin uridine diphosphate-glucuronosyltransferase
RT gene.";
RL Pediatrics 106:E59-E59(2000).
RN [39]
RP VARIANT CN2 GLN-175.
RX PubMed=11370628; DOI=10.1136/jmg.38.4.244;
RA Kadakol A., Sappal B.S., Ghosh S.S., Lowenheim M., Chowdhury A.,
RA Chowdhury S., Santra A., Arias I.M., Chowdhury J.R., Chowdhury N.R.;
RT "Interaction of coding region mutations and the Gilbert-type promoter
RT abnormality of the UGT1A1 gene causes moderate degrees of unconjugated
RT hyperbilirubinaemia and may lead to neonatal kernicterus.";
RL J. Med. Genet. 38:244-249(2001).
RN [40]
RP VARIANT CN2 ASP-400.
RX PubMed=12402338; DOI=10.1002/humu.10122;
RA Labrune P., Myara A., Chalas J., Le Bihan B., Capel L., Francoual J.;
RT "Association of a homozygous (TA)8 promoter polymorphism and a N400D
RT mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome.";
RL Hum. Mutat. 20:399-401(2002).
RN [41]
RP VARIANT GILBS LEU-83.
RX PubMed=12139570; DOI=10.1046/j.1442-200x.2002.01577.x;
RA Sutomo R., Laosombat V., Sadewa A.H., Yokoyama N., Nakamura H., Matsuo M.,
RA Nishio H.;
RT "Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's
RT syndrome.";
RL Pediatr. Int. 44:427-432(2002).
RN [42]
RP CHARACTERIZATION OF VARIANT CN2 ARG-15.
RX PubMed=14550264; DOI=10.1016/j.bbrc.2003.09.072;
RA Ohnishi A., Emi Y.;
RT "Rapid proteasomal degradation of translocation-deficient UDP-
RT glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type
RT II.";
RL Biochem. Biophys. Res. Commun. 310:735-741(2003).
RN [43]
RP VARIANTS CN1 GLN-336; ARG-357; PHE-375; SER-387 AND VAL-395, VARIANTS CN2
RP GLN-34; PHE-170 DEL; TRP-209; GLY-225; LEU-336; TRP-336; ARG-354; CYS-403
RP AND ASP-478, AND VARIANTS CN1/CN2 VAL-377 AND ARG-461.
RX PubMed=15712364; DOI=10.1002/humu.9322;
RA Servedio V., d'Apolito M., Maiorano N., Minuti B., Torricelli F.,
RA Ronchi F., Zancan L., Perrotta S., Vajro P., Boschetto L., Iolascon A.;
RT "Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients:
RT identification of twelve novel alleles and genotype-phenotype
RT correlation.";
RL Hum. Mutat. 25:325-325(2005).
RN [44]
RP VARIANT CN1 PHE-171 DEL, AND VARIANTS CN2 TYR-279; ARG-354; VAL-370;
RP VAL-395; PRO-443 AND ARG-461.
RX PubMed=17229650; DOI=10.3324/haematol.10585;
RA D'Apolito M., Marrone A., Servedio V., Vajro P., De Falco L., Iolascon A.;
RT "Seven novel mutations of the UGT1A1 gene in patients with unconjugated
RT hyperbilirubinemia.";
RL Haematologica 92:133-134(2007).
RN [45]
RP VARIANT CN1 THR-402, VARIANTS CN2 ARG-15; ARG-71; PHE-191; TRP-209;
RP TRP-336; HIS-387; PRO-443 AND ASP-486, CHARACTERIZATION OF VARIANT CN1
RP THR-402, CHARACTERIZATION OF VARIANTS CN2 ARG-71; GLN-175; PHE-191;
RP TRP-209; ARG-331; TRP-336; HIS-387; VAL-395 AND PRO-443, CATALYTIC
RP ACTIVITY, FUNCTION, AND SUBSTRATE SPECIFICITY.
RX PubMed=19830808; DOI=10.1002/humu.21133;
RA Sneitz N., Bakker C.T., de Knegt R.J., Halley D.J., Finel M., Bosma P.J.;
RT "Crigler-Najjar syndrome in The Netherlands: identification of four novel
RT UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of
RT 10 missense mutants.";
RL Hum. Mutat. 31:52-59(2010).
RN [46]
RP VARIANT CN1 ASN-36, AND VARIANT CN2 CYS-230.
RX PubMed=23992562; DOI=10.1111/ahg.12039;
RA Khan S., Irfan M., Sher G., Zubaida B., Alvi M.A., Yasinzai M., Naeem M.;
RT "UGT1A1 gene mutations in Pakistani children suffering from inherited
RT nonhemolytic unconjugated hyperbilirubinemias.";
RL Ann. Hum. Genet. 77:482-487(2013).
RN [47]
RP VARIANTS CN2 PHE-170 DEL AND CYS-367.
RX PubMed=23099197; DOI=10.1016/j.clinbiochem.2012.10.007;
RA Minucci A., Canu G., Gentile L., Cimino V., Giardina B., Zuppi C.,
RA Capoluongo E.;
RT "Identification of a novel mutation in UDP-glucuronosyltransferase (UGT1A1)
RT gene in a child with neonatal unconjugated hyperbilirubinemia.";
RL Clin. Biochem. 46:170-172(2013).
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:18004206,
CC PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867).
CC Essential for the elimination and detoxification of drugs, xenobiotics
CC and endogenous compounds (PubMed:12181437, PubMed:18004206,
CC PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen
CC hormones such as estradiol, estrone and estriol (PubMed:15472229,
CC PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of
CC bilirubin, a degradation product occurring in the normal catabolic
CC pathway that breaks down heme in vertebrates (PubMed:17187418,
CC PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation
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 losartan, 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:18004212,
CC PubMed:20610558). {ECO:0000269|PubMed:12181437,
CC ECO:0000269|PubMed:15472229, ECO:0000269|PubMed:17187418,
CC ECO:0000269|PubMed:18004206, ECO:0000269|PubMed:18004212,
CC ECO:0000269|PubMed:18052087, ECO:0000269|PubMed:18674515,
CC ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19545173,
CC ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:20610558,
CC 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:17187418,
CC ECO:0000269|PubMed:18004212, ECO:0000269|PubMed:20610558}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor
CC beta-D-glucuronoside + H(+) + UDP; Xref=Rhea:RHEA:21032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132367, ChEBI:CHEBI:132368; EC=2.4.1.17;
CC Evidence={ECO:0000269|PubMed:12181437, ECO:0000269|PubMed:15472229,
CC ECO:0000269|PubMed:18004206, ECO:0000269|PubMed:18004212,
CC ECO:0000269|PubMed:18674515, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:12181437, ECO:0000305|PubMed:15472229,
CC ECO:0000305|PubMed:18004206, ECO:0000305|PubMed:18004212,
CC ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:19830808,
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:19830808, 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:19830808, ECO:0000305|PubMed:23288867};
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=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-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=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=16beta,17beta-estriol + UDP-alpha-D-glucuronate =
CC 16beta,17beta-estriol 16-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52880, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:87620, ChEBI:CHEBI:136886;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52881;
CC Evidence={ECO:0000305|PubMed:23288867};
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=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=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 ECO:0000269|PubMed:18004212};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63697;
CC Evidence={ECO:0000305|PubMed:12181437, ECO:0000305|PubMed:18004212};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.26 uM for bilirubin {ECO:0000269|PubMed:18004206};
CC KM=70 uM for 4-methylumbelliferone {ECO:0000269|PubMed:18004206};
CC KM=23 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=38 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:15472229};
CC KM=165 uM for the formation of 2-hydroxy-17beta-estradiol 3-O-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:15472229};
CC KM=15 uM for 2-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 2) {ECO:0000269|PubMed:15472229};
CC KM=19 uM for 2-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=38 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=74 uM for 4-hydroxy-17beta-estradiol (when assaying
CC glucuronidation at position 4) {ECO:0000269|PubMed:15472229};
CC KM=21 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=19 uM for 4-hydroxy-estrone (when assaying glucuronidation at
CC position 4) {ECO:0000269|PubMed:15472229};
CC KM=49 uM for 2-methoxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=49 uM for 2-methoxyestrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=14 uM for 4-methoxy-17beta-estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:15472229};
CC KM=103 uM for 4-methoxyestrone (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:15472229};
CC KM=60.6 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=11.2 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=21.5 uM for losartan (when assaying glucuronidation at position N2
CC of the tetrazole ring) {ECO:0000269|PubMed:18674515};
CC KM=7.5 uM for SN-38 (when assaying glucuronidation at position 10)
CC {ECO:0000269|PubMed:12181437};
CC KM=410 uM for mycophenolate (when assaying glucuronidation at
CC position 7) {ECO:0000269|PubMed:15470161};
CC KM=320 uM for mycophenolate (when assaying glucuronidation at
CC position 6') {ECO:0000269|PubMed:15470161};
CC Vmax=1080 pmol/min/mg enzyme with bilirubin as substrate
CC {ECO:0000269|PubMed:18004206};
CC Vmax=255 pmol/min/mg enzyme with 4-methylumbelliferone as substrate
CC {ECO:0000269|PubMed:18004206};
CC Vmax=274 pmol/min/mg enzyme with 1-naphthol as substrate
CC {ECO:0000269|PubMed:18004206};
CC Vmax=767 pmol/min/mg enzyme with 17beta-estradiol as substrate
CC {ECO:0000269|PubMed:18004206};
CC Vmax=93 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=1037 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=36 pmol/min/mg enzyme for the formation of 2-hydroxy-17beta-
CC estradiol 2-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=326 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=19 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=42 pmol/min/mg enzyme for the formation of 4-hydroxy-17beta-
CC estradiol 4-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=34 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=11 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone 4-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=222 pmol/min/mg enzyme for the formation of 2-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=39 pmol/min/mg enzyme for the formation of 2-methoxyestrone 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=19 pmol/min/mg enzyme for the formation of 4-methoxy-17beta-
CC estradiol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=4 pmol/min/mg enzyme for the formation of 4-methoxyestrone 3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:15472229};
CC Vmax=704 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=115 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=32.2 pmol/min/mg enzyme for the formation of losartan N2-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:18674515};
CC Vmax=40 pmol/min/mg enzyme for the formation of prunetin-4'-O-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:18052087};
CC Vmax=0.014 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=33.4 pmol/min/mg enzyme for the formation of SN-38 glucuronide
CC {ECO:0000269|PubMed:12181437};
CC Vmax=110 pmol/min/mg enzyme for the formation of mycophenolate 7-O-
CC glucuronide {ECO:0000269|PubMed:15470161};
CC Vmax=30 pmol/min/mg enzyme for the formation of mycophenolic acid O-
CC acyl-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:16595710, ECO:0000305|PubMed:18052087};
CC -!- SUBUNIT: Homodimer (PubMed:17179145). Homooligomer (Probable).
CC Interacts with UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and
CC UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts
CC with isoform 2/i2 suggesting that oligomerization is involved in
CC negative regulation of transferase activity by isoform 2
CC (PubMed:17187418, PubMed:20610558). Isoform 1 also interacts with
CC respective i2 isoforms of UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8,
CC UGT1A9 and UGT1A10 (PubMed:20610558). {ECO:0000269|PubMed:17179145,
CC ECO:0000269|PubMed:17187418, ECO:0000269|PubMed:20610558,
CC ECO:0000305|PubMed:20610558}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:17179145, ECO:0000269|PubMed:17187418}; Single-pass
CC membrane protein {ECO:0000255}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:17187418}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=i1 {ECO:0000303|PubMed:18004212};
CC IsoId=P22309-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A1s;
CC IsoId=P22309-2; Sequence=VSP_053958;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in liver, colon and small
CC intestine. Not expressed in kidney, esophagus and skin.
CC {ECO:0000269|PubMed:1339448, ECO:0000269|PubMed:17187418,
CC ECO:0000269|PubMed:18004212}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in liver, colon, small
CC intestine and kidney. Not expressed in esophagus and skin.
CC {ECO:0000269|PubMed:1339448, ECO:0000269|PubMed:17187418,
CC ECO:0000269|PubMed:18004212}.
CC -!- POLYMORPHISM: Genetic variation in UGT1A1 defines the bilirubin serum
CC levels quantitative trait locus 1 (BILIQTL1) [MIM:601816]. Variation in
CC serum bilirubin is associated with altered cardiovascular disease risk
CC and drug metabolism. {ECO:0000269|PubMed:19414484}.
CC -!- DISEASE: Gilbert syndrome (GILBS) [MIM:143500]: Occurs as a consequence
CC of reduced bilirubin transferase activity and is often detected in
CC young adults with vague non-specific complaints.
CC {ECO:0000269|PubMed:11013440, ECO:0000269|PubMed:12139570,
CC ECO:0000269|PubMed:17496722, ECO:0000269|PubMed:7715297,
CC ECO:0000269|PubMed:9627603}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Transient familial neonatal hyperbilirubinemia (HBLRTFN)
CC [MIM:237900]: A condition characterized by excessive concentration of
CC bilirubin in the blood, which may lead to jaundice. Breast milk
CC jaundice is a common problem in nursing infants.
CC {ECO:0000269|PubMed:11061796}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry. The defect has
CC been ascribed to various breast milk substances, but the component or
CC combination of components that is responsible remains unclear. Defects
CC of UGT1A1 are an underlying cause of the prolonged unconjugated
CC hyperbilirubinemia associated with breast milk. One or more components
CC in the milk may trigger the jaundice in infants who have such
CC mutations. Mutations are identical to those detected in patients with
CC Gilbert syndrome, a risk factor of neonatal non-physiologic
CC hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia.
CC -!- DISEASE: Crigler-Najjar syndrome 1 (CN1) [MIM:218800]: Patients have
CC severe hyperbilirubinemia and usually die of kernicterus (bilirubin
CC accumulation in the basal ganglia and brainstem nuclei) within the
CC first year of life. CN1 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11013440, ECO:0000269|PubMed:15712364,
CC ECO:0000269|PubMed:1634050, ECO:0000269|PubMed:17229650,
CC ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:23992562,
CC ECO:0000269|PubMed:7906695, ECO:0000269|PubMed:7989045,
CC ECO:0000269|PubMed:7989595, ECO:0000269|PubMed:8226884}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Crigler-Najjar syndrome 2 (CN2) [MIM:606785]: Patients have
CC less severe hyperbilirubinemia and usually survive into adulthood
CC without neurologic damage. Phenobarbital, which induces the partially
CC deficient glucuronyl transferase, can diminish the jaundice. CN2
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:11013440,
CC ECO:0000269|PubMed:11370628, ECO:0000269|PubMed:12402338,
CC ECO:0000269|PubMed:14550264, ECO:0000269|PubMed:15712364,
CC ECO:0000269|PubMed:17229650, ECO:0000269|PubMed:18004206,
CC ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:23099197,
CC ECO:0000269|PubMed:23992562, ECO:0000269|PubMed:7989595,
CC ECO:0000269|PubMed:8276413, ECO:0000269|PubMed:8280139,
CC ECO:0000269|PubMed:8706880, ECO:0000269|PubMed:9621515,
CC ECO:0000269|PubMed:9639672}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: UGT1A1 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=AAA61247.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAF03522.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glucuronosyltransferase entry;
CC URL="https://en.wikipedia.org/wiki/Glucuronosyltransferase";
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DR EMBL; M57899; AAA63195.1; -; mRNA.
DR EMBL; M84124; AAA61247.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M84122; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; M84123; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; M84125; AAA61248.1; -; Genomic_DNA.
DR EMBL; DQ364247; ABC96771.1; -; mRNA.
DR EMBL; AF297093; AAG30424.1; -; Genomic_DNA.
DR EMBL; AC006985; AAF03522.2; ALT_SEQ; Genomic_DNA.
DR EMBL; D87674; BAA25600.1; -; Genomic_DNA.
DR CCDS; CCDS2510.1; -. [P22309-1]
DR PIR; A39092; A39092.
DR RefSeq; NP_000454.1; NM_000463.2. [P22309-1]
DR AlphaFoldDB; P22309; -.
DR SMR; P22309; -.
DR BioGRID; 120087; 11.
DR ELM; P22309; -.
DR IntAct; P22309; 9.
DR STRING; 9606.ENSP00000304845; -.
DR BindingDB; P22309; -.
DR ChEMBL; CHEMBL1287617; -.
DR DrugBank; DB01048; Abacavir.
DR DrugBank; DB00316; Acetaminophen.
DR DrugBank; DB00173; Adenine.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB00714; Apomorphine.
DR DrugBank; DB12597; Asciminib.
DR DrugBank; DB01072; Atazanavir.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB06626; Axitinib.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB11799; Bictegravir.
DR DrugBank; DB11967; Binimetinib.
DR DrugBank; DB11751; Cabotegravir.
DR DrugBank; DB00564; Carbamazepine.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB11963; Dacomitinib.
DR DrugBank; DB09183; Dasabuvir.
DR DrugBank; DB01609; Deferasirox.
DR DrugBank; DB11943; Delafloxacin.
DR DrugBank; DB00304; Desogestrel.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB08930; Dolutegravir.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB06210; Eltrombopag.
DR DrugBank; DB09101; Elvitegravir.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB00530; Erlotinib.
DR DrugBank; DB11827; Ertugliflozin.
DR DrugBank; DB14575; Eslicarbazepine.
DR DrugBank; DB09119; Eslicarbazepine acetate.
DR DrugBank; DB00783; Estradiol.
DR DrugBank; DB13952; Estradiol acetate.
DR DrugBank; DB13953; Estradiol benzoate.
DR DrugBank; DB13954; Estradiol cypionate.
DR DrugBank; DB13955; Estradiol dienanthate.
DR DrugBank; DB13956; Estradiol valerate.
DR DrugBank; DB00977; Ethinylestradiol.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB00973; Ezetimibe.
DR DrugBank; DB04953; Ezogabine.
DR DrugBank; DB04854; Febuxostat.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00712; Flurbiprofen.
DR DrugBank; DB01095; Fluvastatin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11796; Fostemsavir.
DR DrugBank; DB00947; Fulvestrant.
DR DrugBank; DB00695; Furosemide.
DR DrugBank; DB02703; Fusidic acid.
DR DrugBank; DB06741; Gavestinel.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB13879; Glecaprevir.
DR DrugBank; DB01067; Glipizide.
DR DrugBank; DB12471; Ibrexafungerp.
DR DrugBank; DB05039; Indacaterol.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB01009; Ketoprofen.
DR DrugBank; DB00598; Labetalol.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB00451; Levothyroxine.
DR DrugBank; DB00279; Liothyronine.
DR DrugBank; DB00455; Loratadine.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00227; Lovastatin.
DR DrugBank; DB06077; Lumateperone.
DR DrugBank; DB00916; Metronidazole.
DR DrugBank; DB05018; Migalastat.
DR DrugBank; DB00350; Minoxidil.
DR DrugBank; DB00295; Morphine.
DR DrugBank; DB06510; Muraglitazar.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB01024; Mycophenolic acid.
DR DrugBank; DB01183; Naloxone.
DR DrugBank; DB00704; Naltrexone.
DR DrugBank; DB08804; Nandrolone decanoate.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB04868; Nilotinib.
DR DrugBank; DB09079; Nintedanib.
DR DrugBank; DB00957; Norgestimate.
DR DrugBank; DB09296; Ombitasvir.
DR DrugBank; DB09297; Paritaprevir.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB12978; Pexidartinib.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13878; Pibrentasvir.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB12016; Ponesimod.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB01032; Probenecid.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB00481; Raloxifene.
DR DrugBank; DB06817; Raltegravir.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB01045; Rifampicin.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB12893; Sacituzumab govitecan.
DR DrugBank; DB11689; Selumetinib.
DR DrugBank; DB09298; Silibinin.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB09276; Sodium aurothiomalate.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB00870; Suprofen.
DR DrugBank; DB12020; Tecovirimat.
DR DrugBank; DB00871; Terbutaline.
DR DrugBank; DB01420; Testosterone propionate.
DR DrugBank; DB00906; Tiagabine.
DR DrugBank; DB00932; Tipranavir.
DR DrugBank; DB00193; Tramadol.
DR DrugBank; DB00197; Troglitazone.
DR DrugBank; DB15328; Ubrogepant.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB15456; Vericiguat.
DR DrugBank; DB00495; Zidovudine.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; P22309; -.
DR GuidetoPHARMACOLOGY; 2990; -.
DR SwissLipids; SLP:000001697; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1873; 2 N-Linked glycans (1 site).
DR GlyGen; P22309; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; P22309; -.
DR PhosphoSitePlus; P22309; -.
DR BioMuta; UGT1A1; -.
DR DMDM; 136729; -.
DR jPOST; P22309; -.
DR MassIVE; P22309; -.
DR MaxQB; P22309; -.
DR PaxDb; P22309; -.
DR PeptideAtlas; P22309; -.
DR PRIDE; P22309; -.
DR ProteomicsDB; 1325; -.
DR ProteomicsDB; 53981; -. [P22309-1]
DR Antibodypedia; 35061; 235 antibodies from 27 providers.
DR DNASU; 54658; -.
DR Ensembl; ENST00000305208.10; ENSP00000304845.5; ENSG00000241635.8. [P22309-1]
DR Ensembl; ENST00000360418.4; ENSP00000353593.3; ENSG00000241635.8. [P22309-2]
DR GeneID; 54658; -.
DR KEGG; hsa:54658; -.
DR MANE-Select; ENST00000305208.10; ENSP00000304845.5; NM_000463.3; NP_000454.1.
DR CTD; 54658; -.
DR DisGeNET; 54658; -.
DR GeneCards; UGT1A1; -.
DR HGNC; HGNC:12530; UGT1A1.
DR HPA; ENSG00000241635; Group enriched (intestine, liver).
DR MalaCards; UGT1A1; -.
DR MIM; 143500; phenotype.
DR MIM; 191740; gene.
DR MIM; 218800; phenotype.
DR MIM; 237900; phenotype.
DR MIM; 601816; phenotype.
DR MIM; 606785; phenotype.
DR neXtProt; NX_P22309; -.
DR OpenTargets; ENSG00000241635; -.
DR Orphanet; 79234; Crigler-Najjar syndrome type 1.
DR Orphanet; 79235; Crigler-Najjar syndrome type 2.
DR Orphanet; 357; NON RARE IN EUROPE: Gilbert syndrome.
DR Orphanet; 240885; Prediction of irinotecan toxicity.
DR Orphanet; 240905; Prediction of raltegravir toxicity.
DR Orphanet; 2312; Transient familial neonatal hyperbilirubinemia.
DR PharmGKB; PA37181; -.
DR PharmGKB; PA420; -.
DR VEuPathDB; HostDB:ENSG00000241635; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000159677; -.
DR HOGENOM; CLU_012949_3_2_1; -.
DR InParanoid; P22309; -.
DR OMA; AKVFMTH; -.
DR PhylomeDB; P22309; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; P22309; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-189483; Heme degradation.
DR Reactome; R-HSA-5579002; Defective UGT1A1 causes hyperbilirubinemia.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR Reactome; R-HSA-9753281; Paracetamol ADME.
DR SABIO-RK; P22309; -.
DR SignaLink; P22309; -.
DR SIGNOR; P22309; -.
DR BioGRID-ORCS; 54658; 11 hits in 956 CRISPR screens.
DR GenomeRNAi; 54658; -.
DR Pharos; P22309; Tchem.
DR PRO; PR:P22309; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P22309; protein.
DR Bgee; ENSG00000241635; Expressed in duodenum and 66 other tissues.
DR ExpressionAtlas; P22309; baseline and differential.
DR Genevisible; P22309; HS.
DR GO; GO:0070069; C:cytochrome complex; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA: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:0005496; F:steroid binding; IDA:BHF-UCL.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0006789; P:bilirubin conjugation; TAS:Reactome.
DR GO; GO:0070980; P:biphenyl catabolic process; IEA:Ensembl.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0008210; P:estrogen metabolic process; 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:0046483; P:heterocycle metabolic process; IC:BHF-UCL.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:2001030; P:negative regulation of cellular glucuronidation; IDA:UniProtKB.
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:0045939; P:negative regulation of steroid metabolic process; IC:BHF-UCL.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR GO; GO:0042573; P:retinoic acid metabolic process; IC:BHF-UCL.
DR GO; GO:0008202; P:steroid metabolic process; IC:BHF-UCL.
DR GO; GO:0052697; P:xenobiotic glucuronidation; IDA:UniProtKB.
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; Cytoplasm; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Lipid metabolism; Membrane;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..533
FT /note="UDP-glucuronosyltransferase 1A1"
FT /id="PRO_0000036000"
FT TRANSMEM 491..507
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 435..533
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053958"
FT VARIANT 15
FT /note="L -> R (in CN2; mutant protein rapidly degraded by
FT the proteasome owing to its mislocalization in the cell;
FT dbSNP:rs111033541)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:14550264, ECO:0000269|PubMed:19830808,
FT ECO:0000269|PubMed:8706880"
FT /id="VAR_019410"
FT VARIANT 34
FT /note="P -> Q (in CN2)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026134"
FT VARIANT 36
FT /note="D -> N (in CN1)"
FT /evidence="ECO:0000269|PubMed:23992562"
FT /id="VAR_071402"
FT VARIANT 39
FT /note="H -> D (in CN1; dbSNP:rs72551339)"
FT /evidence="ECO:0000269|PubMed:11013440"
FT /id="VAR_026135"
FT VARIANT 71
FT /note="G -> R (in CN2, GILBS and HBLRTFN; has significant
FT residual bilirubin glucuronidation activity of about 25% to
FT 50% of that of the wild-type protein; displays no change in
FT biluribin affinity; dbSNP:rs4148323)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:11061796, ECO:0000269|PubMed:18004206,
FT ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:7715297,
FT ECO:0000269|PubMed:8280139, ECO:0000269|PubMed:9621515"
FT /id="VAR_009504"
FT VARIANT 83
FT /note="F -> L (in GILBS; displays less than 10% of wild-
FT type bilirubin glucuronidation activity; dbSNP:rs56059937)"
FT /evidence="ECO:0000269|PubMed:12139570,
FT ECO:0000269|PubMed:18004206"
FT /id="VAR_026136"
FT VARIANT 170
FT /note="Missing (in CN1 and CN2; has nearly normal activity
FT at pH 7.6 and is inactive at pH 6.4)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364, ECO:0000269|PubMed:23099197,
FT ECO:0000269|PubMed:7989595, ECO:0000269|PubMed:8226884"
FT /id="VAR_007695"
FT VARIANT 171
FT /note="Missing (in CN2; dbSNP:rs587776762)"
FT /evidence="ECO:0000269|PubMed:17229650"
FT /id="VAR_064955"
FT VARIANT 175
FT /note="L -> Q (in CN2; has low residual bilirubin
FT glucuronidation activity of about 4.6% of that of the wild-
FT type protein; dbSNP:rs72551341)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:11370628, ECO:0000269|PubMed:19830808,
FT ECO:0000269|PubMed:7989595"
FT /id="VAR_019411"
FT VARIANT 177
FT /note="C -> R (in CN1; dbSNP:rs72551342)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989595"
FT /id="VAR_007697"
FT VARIANT 191
FT /note="S -> F (in CN2; has low residual bilirubin
FT glucuronidation activity of about 5.3% of that of the wild-
FT type protein)"
FT /evidence="ECO:0000269|PubMed:19830808"
FT /id="VAR_064956"
FT VARIANT 209
FT /note="R -> W (in CN2; has low residual bilirubin
FT glucuronidation activity of about 2.9% of that of the wild-
FT type protein; dbSNP:rs72551343)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364, ECO:0000269|PubMed:19830808,
FT ECO:0000269|PubMed:7989595, ECO:0000269|PubMed:9621515"
FT /id="VAR_007698"
FT VARIANT 225
FT /note="V -> G (in CN2; dbSNP:rs35003977)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364"
FT /id="VAR_026137"
FT VARIANT 229
FT /note="P -> Q (in CN2 and GILBS; displays 2-fold decrease
FT in biluribin affinity and 61% of wild-type bilirubin
FT glucuronidation activity; dbSNP:rs35350960)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:18004206, ECO:0000269|PubMed:7715297,
FT ECO:0000269|PubMed:9621515"
FT /id="VAR_009505"
FT VARIANT 230
FT /note="Y -> C (in CN2; dbSNP:rs754922685)"
FT /evidence="ECO:0000269|PubMed:23992562"
FT /id="VAR_071403"
FT VARIANT 276
FT /note="G -> R (in CN1; dbSNP:rs72551345)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989595"
FT /id="VAR_007699"
FT VARIANT 279
FT /note="N -> Y (in CN2; dbSNP:rs397978903)"
FT /evidence="ECO:0000269|PubMed:17229650"
FT /id="VAR_064957"
FT VARIANT 291
FT /note="E -> V (in CN1)"
FT /evidence="ECO:0000269|PubMed:11013440"
FT /id="VAR_026138"
FT VARIANT 292
FT /note="A -> V (in CN1; dbSNP:rs758873309)"
FT /evidence="ECO:0000269|PubMed:7989045"
FT /id="VAR_007700"
FT VARIANT 294
FT /note="I -> T (in GILBS and CN2; 40-55% normal bilirubin
FT glucuronidation activity; normal Km for bilirubin; when
FT homozygous far less repressive and generates the mild
FT Gilbert phenotype; dbSNP:rs72551347)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:9639672"
FT /id="VAR_026139"
FT VARIANT 308
FT /note="G -> E (in CN1; no bilirubin glucuronidation
FT activity; dbSNP:rs62625011)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7906695, ECO:0000269|PubMed:7989045"
FT /id="VAR_007701"
FT VARIANT 331
FT /note="Q -> R (in CN2; has no residual bilirubin
FT glucuronidation activity; dbSNP:rs72551348)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:8276413"
FT /id="VAR_007702"
FT VARIANT 336
FT /note="R -> L (in CN1 and CN2)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026140"
FT VARIANT 336
FT /note="R -> Q (in CN1; dbSNP:rs750453538)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026141"
FT VARIANT 336
FT /note="R -> W (in CN2; has very low residual bilirubin
FT glucuronidation activity of about 0.4% of that of the wild-
FT type protein; dbSNP:rs139607673)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364, ECO:0000269|PubMed:19830808"
FT /id="VAR_026142"
FT VARIANT 354
FT /note="W -> R (in CN2; dbSNP:rs1559414817)"
FT /evidence="ECO:0000269|PubMed:15712364,
FT ECO:0000269|PubMed:17229650"
FT /id="VAR_026143"
FT VARIANT 357
FT /note="Q -> R (in CN1; dbSNP:rs72551351)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364, ECO:0000269|PubMed:7989045"
FT /id="VAR_007703"
FT VARIANT 367
FT /note="R -> C (in CN2; dbSNP:rs55750087)"
FT /evidence="ECO:0000269|PubMed:23099197"
FT /id="VAR_071404"
FT VARIANT 367
FT /note="R -> G (in GILBS; dbSNP:rs55750087)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7715297"
FT /id="VAR_012283"
FT VARIANT 368
FT /note="A -> T (in CN1; dbSNP:rs72551352)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989045"
FT /id="VAR_007704"
FT VARIANT 370
FT /note="I -> V (in CN2; dbSNP:rs748989741)"
FT /evidence="ECO:0000269|PubMed:17229650"
FT /id="VAR_064958"
FT VARIANT 375
FT /note="S -> F (in CN1; no bilirubin glucuronidation
FT activity; dbSNP:rs72551353)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364, ECO:0000269|PubMed:1634050,
FT ECO:0000269|PubMed:7906695, ECO:0000269|PubMed:7989595"
FT /id="VAR_007705"
FT VARIANT 376
FT /note="H -> R (in CN1 and CN2; dbSNP:rs1349037761)"
FT /id="VAR_026144"
FT VARIANT 377
FT /note="G -> V (in CN1 and CN2; dbSNP:rs1283652721)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026145"
FT VARIANT 381
FT /note="S -> R (in CN1; dbSNP:rs72551354)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989045"
FT /id="VAR_007706"
FT VARIANT 387
FT /note="P -> H (in CN2; has no residual bilirubin
FT glucuronidation activity)"
FT /evidence="ECO:0000269|PubMed:19830808"
FT /id="VAR_064959"
FT VARIANT 387
FT /note="P -> S (in CN1; dbSNP:rs901936528)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:15712364"
FT /id="VAR_026146"
FT VARIANT 395
FT /note="G -> V (in CN1; has no residual bilirubin
FT glucuronidation activity; dbSNP:rs367897068)"
FT /evidence="ECO:0000269|PubMed:15712364,
FT ECO:0000269|PubMed:17229650, ECO:0000269|PubMed:19830808"
FT /id="VAR_026147"
FT VARIANT 400
FT /note="N -> D (in CN2; dbSNP:rs28934877)"
FT /evidence="ECO:0000269|PubMed:12402338"
FT /id="VAR_019412"
FT VARIANT 401
FT /note="A -> P (in CN1; dbSNP:rs72551355)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989045"
FT /id="VAR_007707"
FT VARIANT 402
FT /note="K -> T (in CN1; has no residual bilirubin
FT glucuronidation activity; N-glycosylation does take place
FT at this new additional site)"
FT /evidence="ECO:0000269|PubMed:19830808"
FT /id="VAR_064960"
FT VARIANT 403
FT /note="R -> C (in CN2; dbSNP:rs778766461)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026148"
FT VARIANT 428
FT /note="K -> E (in CN1; dbSNP:rs72551356)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:7989045"
FT /id="VAR_007708"
FT VARIANT 443
FT /note="L -> P (in CN2; has no residual bilirubin
FT glucuronidation activity; dbSNP:rs758411577)"
FT /evidence="ECO:0000269|PubMed:17229650,
FT ECO:0000269|PubMed:19830808"
FT /id="VAR_064961"
FT VARIANT 461
FT /note="W -> R (in CN1 and CN2; dbSNP:rs1476500325)"
FT /evidence="ECO:0000269|PubMed:15712364,
FT ECO:0000269|PubMed:17229650"
FT /id="VAR_026149"
FT VARIANT 478
FT /note="A -> D (in CN2)"
FT /evidence="ECO:0000269|PubMed:15712364"
FT /id="VAR_026150"
FT VARIANT 486
FT /note="Y -> D (in CN2, GILBS and HBLRTFN; displays less
FT than 10% of wild-type bilirubin glucuronidation activity;
FT dbSNP:rs34993780)"
FT /evidence="ECO:0000269|PubMed:11013440,
FT ECO:0000269|PubMed:11061796, ECO:0000269|PubMed:18004206,
FT ECO:0000269|PubMed:19830808, ECO:0000269|PubMed:8280139,
FT ECO:0000269|PubMed:9621515, ECO:0000269|PubMed:9627603"
FT /id="VAR_007709"
FT VARIANT 511
FT /note="A -> P (in dbSNP:rs1042709)"
FT /id="VAR_025355"
FT MUTAGEN 71
FT /note="G->R: Decreased SN-38 glucuronosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12181437"
FT MUTAGEN 229
FT /note="P->Q: Decreased SN-38 glucuronosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12181437"
FT MUTAGEN 233
FT /note="L->R: Decreased SN-38 glucuronosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12181437"
FT MUTAGEN 486
FT /note="Y->D: Decreased SN-38 glucuronosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:12181437"
SQ SEQUENCE 533 AA; 59591 MW; 19C90231AD0EB547 CRC64;
MAVESQGGRP LVLGLLLCVL GPVVSHAGKI LLIPVDGSHW LSMLGAIQQL QQRGHEIVVL
APDASLYIRD GAFYTLKTYP VPFQREDVKE SFVSLGHNVF ENDSFLQRVI KTYKKIKKDS
AMLLSGCSHL LHNKELMASL AESSFDVMLT DPFLPCSPIV AQYLSLPTVF FLHALPCSLE
FEATQCPNPF SYVPRPLSSH SDHMTFLQRV KNMLIAFSQN FLCDVVYSPY ATLASEFLQR
EVTVQDLLSS ASVWLFRSDF VKDYPRPIMP NMVFVGGINC LHQNPLSQEF EAYINASGEH
GIVVFSLGSM VSEIPEKKAM AIADALGKIP QTVLWRYTGT RPSNLANNTI LVKWLPQNDL
LGHPMTRAFI THAGSHGVYE SICNGVPMVM MPLFGDQMDN AKRMETKGAG VTLNVLEMTS
EDLENALKAV INDKSYKENI MRLSSLHKDR PVEPLDLAVF WVEFVMRHKG APHLRPAAHD
LTWYQYHSLD VIGFLLAVVL TVAFITFKCC AYGYRKCLGK KGRVKKAHKS KTH
