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 27-MAR-2024, entry version 231. 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.t01-1-01577.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 CC 3-O-(beta-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 CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=3 pmol/min/mg enzyme for the formation of estrone CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=1037 pmol/min/mg enzyme for the formation of CC 2-hydroxy-17beta-estradiol 3-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=36 pmol/min/mg enzyme for the formation of CC 2-hydroxy-17beta-estradiol 2-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=326 pmol/min/mg enzyme for the formation of 2-hydroxy-estrone CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=19 pmol/min/mg enzyme for the formation of CC 4-hydroxy-17beta-estradiol 3-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=42 pmol/min/mg enzyme for the formation of CC 4-hydroxy-17beta-estradiol 4-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=34 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=11 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone CC 4-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=222 pmol/min/mg enzyme for the formation of CC 2-methoxy-17beta-estradiol 3-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=39 pmol/min/mg enzyme for the formation of 2-methoxyestrone CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=19 pmol/min/mg enzyme for the formation of CC 4-methoxy-17beta-estradiol 3-O-(beta-D-glucuronate) CC {ECO:0000269|PubMed:15472229}; CC Vmax=4 pmol/min/mg enzyme for the formation of 4-methoxyestrone CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:15472229}; CC Vmax=704 pmol/min/mg enzyme for the formation of 17beta-estradiol CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240}; CC Vmax=115 pmol/min/mg enzyme for the formation of 17alpha-estradiol CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240}; CC Vmax=32.2 pmol/min/mg enzyme for the formation of losartan CC N2-(beta-D-glucuronate) {ECO:0000269|PubMed:18674515}; CC Vmax=40 pmol/min/mg enzyme for the formation of CC prunetin-4'-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18052087}; CC Vmax=0.014 pmol/min/mg enzyme with 5alpha-dihydrotestosterone CC 17-O-(beta-D-glucuronate) as substrate, for the formation of CC 5alpha-dihydrotestosterone CC 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 CC 7-O-glucuronide {ECO:0000269|PubMed:15470161}; CC Vmax=30 pmol/min/mg enzyme for the formation of mycophenolic acid CC O-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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; DB08912; Dabrafenib. 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; DB00470; Dronabinol. DR DrugBank; DB12243; Edaravone. 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; DB15673; Lenacapavir. 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; DB16236; Mitapivat. 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; DB09074; Olaparib. 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; DB12713; Sotagliflozin. 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 GlyCosmos; P22309; 3 sites, 2 glycans. DR GlyGen; P22309; 4 sites, 2 N-linked glycans (1 site), 1 O-linked glycan (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; 9606-ENSP00000304845; -. DR PeptideAtlas; P22309; -. DR ProteomicsDB; 1325; -. DR ProteomicsDB; 53981; -. [P22309-1] DR Antibodypedia; 35061; 266 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 AGR; HGNC:12530; -. 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; 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; SFRTEIY; -. DR OrthoDB; 382054at2759; -. 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 1034 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 cell types or tissues. DR ExpressionAtlas; P22309; baseline and differential. 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:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. 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 Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2. DR InterPro; IPR002213; UDP_glucos_trans. DR InterPro; IPR035595; UDP_glycos_trans_CS. DR PANTHER; PTHR48043; EG:EG0003.4 PROTEIN-RELATED; 1. DR PANTHER; PTHR48043:SF157; UDP GLUCURONOSYLTRANSFERASE 1 FAMILY POLYPEPTIDE A3 PRECURSOR-RELATED; 1. DR Pfam; PF00201; UDPGT; 1. DR SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 1. DR PROSITE; PS00375; UDPGT; 1. DR Genevisible; P22309; HS. 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 FT wild-type bilirubin glucuronidation activity; FT 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 FT wild-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 FT wild-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 FT wild-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 FT wild-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 //