UDP-glucuronosyltransferase 1-9

Details

Name
UDP-glucuronosyltransferase 1-9
Synonyms
  • 2.4.1.17
  • GNT1
  • lugP4
  • UDP-glucuronosyltransferase 1-I
  • UDP-glucuronosyltransferase 1A9
  • UDPGT 1-9
  • UGT-1I
  • UGT1
  • UGT1I
Gene Name
UGT1A9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006817|UDP-glucuronosyltransferase 1-9
MACTGWTSPLPLCVCLLLTCGFAEAGKLLVVPMDGSHWFTMRSVVEKLILRGHEVVVVMP
EVSWQLGRSLNCTVKTYSTSYTLEDLDREFKAFAHAQWKAQVRSIYSLLMGSYNDIFDLF
FSNCRSLFKDKKLVEYLKESSFDAVFLDPFDNCGLIVAKYFSLPSVVFARGILCHYLEEG
AQCPAPLSYVPRILLGFSDAMTFKERVRNHIMHLEEHLLCHRFFKNALEIASEILQTPVT
EYDLYSHTSIWLLRTDFVLDYPKPVMPNMIFIGGINCHQGKPLPMEFEAYINASGEHGIV
VFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGH
PMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDL
ENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTW
YQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues
530
Molecular Weight
59940.495
Theoretical pI
7.96
GO Classification
Functions
enzyme binding / enzyme inhibitor activity / glucuronosyltransferase activity / protein heterodimerization activity / protein homodimerization activity / retinoic acid binding
Processes
cellular glucuronidation / cellular lipid metabolic process / cellular response to hormone stimulus / flavone metabolic process / flavonoid biosynthetic process / flavonoid glucuronidation / metabolic process / negative regulation of cellular glucuronidation / negative regulation of fatty acid metabolic process / negative regulation of glucuronosyltransferase activity / retinoic acid metabolic process / small molecule metabolic process / xenobiotic glucuronidation / xenobiotic metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / extracellular exosome / integral component of membrane
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Pfam Domain Function
Transmembrane Regions
488-504
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0012464|UDP-glucuronosyltransferase 1-9 (UGT1A9)
ATGGCTTGCACAGGGTGGACCAGCCCCCTTCCTCTATGTGTGTGTCTGCTGCTGACCTGT
GGCTTTGCCGAGGCAGGGAAGCTACTGGTAGTGCCCATGGATGGGAGCCACTGGTTCACC
ATGAGGTCGGTGGTGGAGAAACTCATTCTCAGGGGGCATGAGGTGGTTGTAGTCATGCCA
GAGGTGAGTTGGCAACTGGGAAGATCACTGAATTGCACAGTGAAGACTTATTCAACTTCA
TATACCCTGGAGGATCTGGACCGGGAGTTCAAGGCTTTTGCCCATGCTCAATGGAAAGCA
CAAGTACGAAGTATATATTCTCTATTAATGGGTTCATACAATGACATTTTTGACTTATTT
TTTTCAAATTGCAGGAGTTTGTTTAAAGACAAAAAATTAGTAGAATACTTAAAGGAGAGT
TCTTTTGATGCAGTGTTTCTCGATCCTTTTGATAACTGTGGCTTAATTGTTGCCAAATAT
TTCTCCCTCCCCTCCGTGGTCTTCGCCAGGGGAATACTTTGCCACTATCTTGAAGAAGGT
GCACAGTGCCCTGCTCCTCTTTCCTATGTCCCCAGAATTCTCTTAGGGTTCTCAGATGCC
ATGACTTTCAAGGAGAGAGTACGGAACCACATCATGCACTTGGAGGAACATTTATTATGC
CACCGTTTTTTCAAAAATGCCCTAGAAATAGCCTCTGAAATTCTCCAAACACCTGTTACG
GAGTATGATCTCTACAGCCACACATCAATTTGGTTGTTGCGAACGGACTTTGTTTTGGAC
TATCCCAAACCCGTGATGCCCAACATGATCTTCATTGGTGGTATCAACTGCCATCAGGGA
AAGCCGTTGCCTATGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACATGGAATTGTG
GTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCTATGGCAATTGCT
GATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGAACCCGACCATCG
AATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGATCTGCTTGGTCAC
CCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTATGAAAGCATATGC
AATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGACAATGCAAAGCGC
ATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCTGAAGATTTA
GAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAACATCATGCGCCTC
TCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTGTTCTGGGTGGAG
TTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCACGACCTCACCTGG
TACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTGCTGACAGTGGCC
TTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGGAAAAAAGGGCGA
GTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Chromosome Location
2
Locus
2q37
External Identifiers
ResourceLink
UniProtKB IDO60656
UniProtKB Entry NameUD19_HUMAN
GenBank Protein ID7690346
GenBank Gene IDS55985
HGNC IDHGNC:12541
General References
  1. Wooster R, Sutherland L, Ebner T, Clarke D, Da Cruz e Silva O, Burchell B: Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family. Biochem J. 1991 Sep 1;278 ( Pt 2):465-9. [PubMed:1910331]
  2. 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. [PubMed:11434514]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  5. 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. [PubMed:18004212]
  6. 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. [PubMed:19545173]
  7. Bellemare J, Rouleau M, Girard H, Harvey M, Guillemette C: Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro. Drug Metab Dispos. 2010 Oct;38(10):1785-9. doi: 10.1124/dmd.110.034835. Epub 2010 Jul 7. [PubMed:20610558]
  8. Nakajima M, Koga T, Sakai H, Yamanaka H, Fujiwara R, Yokoi T: N-Glycosylation plays a role in protein folding of human UGT1A9. Biochem Pharmacol. 2010 Apr 15;79(8):1165-72. doi: 10.1016/j.bcp.2009.11.020. Epub 2009 Nov 29. [PubMed:19951703]
  9. 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. [PubMed:24275569]
  10. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974]
  11. Menard V, Girard H, Harvey M, Perusse L, Guillemette C: Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population. Hum Mutat. 2009 Apr;30(4):677-87. doi: 10.1002/humu.20946. [PubMed:19204906]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00398Sorafenibapproved, investigationalunknownsubstrateinhibitorDetails
DB00328Indometacinapproved, investigationalunknownsubstrateDetails
DB00494Entacaponeapproved, investigationalunknownsubstrateDetails
DB00749Etodolacapproved, investigational, vet_approvedunknownsubstrateDetails
DB00762Irinotecanapproved, investigationalunknownsubstrateDetails
DB00818Propofolapproved, investigational, vet_approvedunknownsubstrateDetails
DB01024Mycophenolic acidapprovedunknownsubstrateDetails
DB01015SulfamethoxazoleapprovedunknownsubstrateDetails
DB00313Valproic Acidapproved, investigationalunknownsubstrateDetails
DB00502HaloperidolapprovedunknownsubstrateDetails
DB00744Zileutonapproved, investigational, withdrawnunknownsubstrateDetails
DB00712Flurbiprofenapproved, investigationalunknownsubstrateDetails
DB01050IbuprofenapprovedunknownsubstrateDetails
DB01283Lumiracoxibapproved, investigationalunknownsubstrateDetails
DB00580Valdecoxibapproved, investigational, withdrawnunknownsubstrateDetails
DB00921Buprenorphineapproved, illicit, investigational, vet_approvedunknownsubstrateDetails
DB00731Nateglinideapproved, investigationalunknownsubstrateDetails
DB06739SeratrodastexperimentalunknownsubstrateDetails
DB06741GavestinelinvestigationalunknownsubstrateDetails
DB06738KetobemidoneinvestigationalunknownsubstrateDetails
DB06403Ambrisentanapproved, investigationalunknownsubstrateDetails
DB00197Troglitazoneinvestigational, withdrawnunknownsubstrateDetails
DB00688Mycophenolate mofetilapproved, investigationalunknownsubstrateDetails
DB04824Phenolphthaleinapproved, withdrawnunknownDetails
DB04552Niflumic acidexperimentalunknownDetails
DB06235VadimezaninvestigationalunknownDetails
DB04953Ezogabineapproved, investigationalunknownsubstrateDetails
DB06204TapentadolapprovedunknownsubstrateDetails
DB06695Dabigatran etexilateapprovedunknownsubstrateDetails
DB08896RegorafenibapprovedunknownsubstrateinhibitorDetails
DB08907CanagliflozinapprovedunknownsubstrateDetails
DB00316AcetaminophenapprovedunknownsubstrateDetails
DB00842OxazepamapprovedunknownsubstrateDetails
DB06292DapagliflozinapprovednosubstrateDetails
DB01685TopiroxostatexperimentalunknownsubstrateDetails
DB13874Enasidenibapproved, investigationalunknownsubstrateDetails
DB08930DolutegravirapprovednosubstrateDetails
DB11827Ertugliflozinapproved, investigationalnosubstrateDetails
DB11638Artenimolexperimental, investigationalnosubstrateDetails
DB11633Isavuconazoleapproved, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknownsubstrateDetails
DB01320Fosphenytoinapproved, investigationalnoinhibitorDetails
DB00252Phenytoinapproved, vet_approvednoinhibitorDetails
DB09288PropacetamolexperimentalnosubstrateDetails
DB01609Deferasiroxapproved, investigationalunknowninhibitorDetails
DB09213Dexibuprofenapproved, investigationalunknownDetails
DB06210EltrombopagapprovednoinhibitorDetails
DB00784Mefenamic acidapprovednoinhibitorDetails
DB00861Diflunisalapproved, investigationalnoinhibitorDetails
DB04552Niflumic acidexperimentalnoinhibitorDetails
DB11978Glasdegibapproved, investigationalnosubstrateDetails
DB00788Naproxenapproved, vet_approvedunknownDetails