UDP-glucuronosyltransferase 1-1


NameUDP-glucuronosyltransferase 1-1
Synonyms2.4.1.17 Bilirubin-specific UDPGT isozyme 1 GNT1 hUG-BR1 UDP-glucuronosyltransferase 1-A UDP-glucuronosyltransferase 1A1 UDPGT 1-1 UGT-1A UGT1 UGT1A
Gene NameUGT1A1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0006823|UDP-glucuronosyltransferase 1-1
MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL
APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS
AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE
FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR
EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH
GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL
LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS
EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD
LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues533
Molecular Weight59590.91
Theoretical pI8.09
GO Classification
Functions
    protein heterodimerization activity
    enzyme inhibitor activity
    retinoic acid binding
    glucuronosyltransferase activity
    enzyme binding
    protein homodimerization activity
    steroid binding
Processes
    acute-phase response
    organ regeneration
    response to drug
    flavonoid biosynthetic process
    cellular response to glucocorticoid stimulus
    flavonoid glucuronidation
    cellular response to hormone stimulus
    negative regulation of cellular glucuronidation
    response to lipopolysaccharide
    retinoic acid metabolic process
    negative regulation of fatty acid metabolic process
    xenobiotic metabolic process
    heme catabolic process
    negative regulation of glucuronosyltransferase activity
    estrogen metabolic process
    cellular response to ethanol
    digestion
    xenobiotic glucuronidation
    liver development
    small molecule metabolic process
    response to nutrient
    negative regulation of catalytic activity
    bilirubin conjugation
    drug metabolic process
    heterocycle metabolic process
    biphenyl catabolic process
    response to starvation
    cellular glucuronidation
    steroid metabolic process
    negative regulation of steroid metabolic process
    porphyrin-containing compound metabolic process
    flavone metabolic process
Components
    endoplasmic reticulum membrane
    endoplasmic reticulum chaperone complex
    cytochrome complex
    integral component of plasma membrane
    endoplasmic reticulum
General FunctionSteroid binding
Specific FunctionUDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Transmembrane Regions491-507
GenBank Protein ID184473
UniProtKB IDP22309
UniProtKB Entry NameUD11_HUMAN
Cellular LocationMicrosome
Gene sequence
>lcl|BSEQ0021360|UDP-glucuronosyltransferase 1-1 (UGT1A1)
ATGGCTGTGGAGTCCCAGGGCGGACGCCCACTTGTCCTGGGCCTGCTGCTGTGTGTGCTG
GGCCCAGTGGTGTCCCATGCTGGGAAGATACTGTTGATCCCAGTGGATGGCAGCCACTGG
CTGAGCATGCTTGGGGCCATCCAGCAGCTGCAGCAGAGGGGACATGAAATAGTTGTCCTA
GCACCTGACGCCTCGTTGTACATCAGAGACGGAGCATTTTACACCTTGAAGACGTACCCT
GTGCCATTCCAAAGGGAGGATGTGAAAGAGTCTTTTGTTAGTCTCGGGCATAATGTTTTT
GAGAATGATTCTTTCCTGCAGCGTGTGATCAAAACATACAAGAAAATAAAAAAGGACTCT
GCTATGCTTTTGTCTGGCTGTTCCCACTTACTGCACAACAAGGAGCTCATGGCCTCCCTG
GCAGAAAGCAGCTTTGATGTCATGCTGACGGACCCTTTCCTTCCTTGCAGCCCCATCGTG
GCCCAGTACCTGTCTCTGCCCACTGTATTCTTCTTGCATGCACTGCCATGCAGCCTGGAA
TTTGAGGCTACCCAGTGCCCCAACCCATTCTCCTACGTGCCCAGGCCTCTCTCCTCTCAT
TCAGATCACATGACCTTCCTGCAGCGGGTGAAGAACATGCTCATTGCCTTTTCACAGAAC
TTTCTGTGCGACGTGGTTTATTCCCCGTATGCAACCCTTGCCTCAGAATTCCTTCAGAGA
GAGGTGACTGTCCAGGACCTATTGAGCTCTGCATCTGTCTGGCTGTTTAGAAGTGACTTT
GTGAAGGATTACCCTAGGCCCATCATGCCCAATATGGTTTTTGTTGGTGGAATCAACTGC
CTTCACCAAAATCCACTATCCCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACAT
GGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCTATG
GCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGAACC
CGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGATCTG
CTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTATGAA
AGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGACAAT
GCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCT
GAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAACATC
ATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTGTTC
TGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCACGAC
CTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTGCTG
ACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGGAAA
AAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
GenBank Gene IDM57899
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:12530
Chromosome Location2
Locus2q37
References
  1. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS: A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem. 1992 Feb 15;267(5):3257-61.[1339448 ]
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  3. Ciotti M, Chen F, Rubaltelli FF, Owens IS: Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease. Biochim Biophys Acta. 1998 Jul 1;1407(1):40-50.[9639672 ]
  4. Ritter JK, Crawford JM, Owens IS: Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells. J Biol Chem. 1991 Jan 15;266(2):1043-7.[1898728 ]
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  6. Johnson AD, Kavousi M, Smith AV, Chen MH, Dehghan A, Aspelund T, Lin JP, van Duijn CM, Harris TB, Cupples LA, Uitterlinden AG, Launer L, Hofman A, Rivadeneira F, Stricker B, Yang Q, O'Donnell CJ, Gudnason V, Witteman JC: Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet. 2009 Jul 15;18(14):2700-10. doi: 10.1093/hmg/ddp202. Epub 2009 May 4.[19414484 ]
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  8. Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC: Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus. Pharmacogenetics. 2001 Jun;11(4):357-68.[11434514 ]
  9. Meunier L, Usherwood YK, Chung KT, Hendershot LM: A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Mol Biol Cell. 2002 Dec;13(12):4456-69.[12475965 ]
  10. Levesque E, Girard H, Journault K, Lepine J, Guillemette C: Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing event at the UGT1A locus. Hepatology. 2007 Jan;45(1):128-38.[17187418 ]
  11. Udomuksorn W, Elliot DJ, Lewis BC, Mackenzie PI, Yoovathaworn K, Miners JO: Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates. Pharmacogenet Genomics. 2007 Dec;17(12):1017-29.[18004206 ]
  12. Girard H, Levesque E, Bellemare J, Journault K, Caillier B, Guillemette C: Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity. Pharmacogenet Genomics. 2007 Dec;17(12):1077-89.[18004212 ]
  13. Tang L, Singh R, Liu Z, Hu M: Structure and concentration changes affect characterization of UGT isoform-specific metabolism of isoflavones. Mol Pharm. 2009 Sep-Oct;6(5):1466-82. doi: 10.1021/mp8002557.[19545173 ]
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  15. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22.[24275569 ]
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  17. Aono S, Yamada Y, Keino H, Hanada N, Nakagawa T, Sasaoka Y, Yazawa T, Sato H, Koiwai O: Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1239-44.[8280139 ]
  18. Moghrabi N, Clarke DJ, Boxer M, Burchell B: Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2. Genomics. 1993 Oct;18(1):171-3.[8276413 ]
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  23. Aono S, Adachi Y, Uyama E, Yamada Y, Keino H, Nanno T, Koiwai O, Sato H: Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome. Lancet. 1995 Apr 15;345(8955):958-9.[7715297 ]
  24. Seppen J, Steenken E, Lindhout D, Bosma PJ, Elferink RP: A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II. FEBS Lett. 1996 Jul 29;390(3):294-8.[8706880 ]
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Related FRC


FRCD ID Name Exact Mass Structure



Guthion




317.318



Dicofol




370.475



Fenoxycarb




301.342



Thiobencarb




257.776



Cypermethrin




416.298



Cyfluthrin




434.288



Butachlor




311.85



Fenpropathrin




349.43



Clofentezine




303.146



Cyanazine




240.695



Ethalfluralin




333.267



Etoxazole




359.417



Fenitrothion




277.24



Flutolanil




323.315



Penoxsulam




483.37



Sulfentrazone




387.183



Tebufenozide




352.478



Butralin




295.339



Coumaphos




362.761



Cyproconazole




291.779



Forchlorfenuron




247.682



Prallethrin




300.398



Profenofos




373.626



Propyzamide




256.126



Pyrimethanil




199.257



Triadimefon




293.751



Triadimenol




295.767



Triticonazole




317.817



Disulfoton




274.392



Diazinon




304.35



Methoxychlor




345.644



Parathion




291.258



Asulam




230.238



Benomyl




290.323



Carbaril




201.225



Chlorpropham




213.661



Metolachlor




283.796



Fenthion




278.321



Ametryn




227.33



Benfluralin




335.283



Bensulide




397.503



Boscalid




343.207



Bromacil




261.119



Cinmethylin




274.404



Cyprodinil




225.295



Dichloran




207.01



Diclosulam




406.213



Dimethenamid




275.791



Indoxacarb




527.837



Iprodione




330.165



Isoxaben




332.4



Lactofen




461.774



Methidathion




302.318



Methoxyfenozide




368.477



Napropamide




271.36



Norflurazon




303.669



Phosalone




367.799



Prometryn




241.357



Propargite




350.473



Propazine




229.712



Pyraclostrobin




387.82



Pyriproxyfen




321.376



Tebupirimfos




318.372



Thiazopyr




396.376



Atrazine




215.685



Chlorethoxyfos




335.985



Clopyralid




191.995



Dithiopyr




401.41



Diuron




233.092



Fludioxonil




248.189



Isazofos




313.737



Linuron




249.091



Quinoxyfen




308.133



Thidiazuron




220.25



Triflumizole




345.75



Trifluralin




335.283