UDP-glucuronosyltransferase 1-6

Details

Name
UDP-glucuronosyltransferase 1-6
Synonyms
  • 2.4.1.17
  • GNT1
  • Phenol-metabolizing UDP-glucuronosyltransferase
  • UDP-glucuronosyltransferase 1-F
  • UDP-glucuronosyltransferase 1A6
  • UDPGT 1-6
  • UGT-1F
  • UGT1
  • UGT1F
Gene Name
UGT1A6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008545|UDP-glucuronosyltransferase 1-6
MACLLRSFQRISAGVFFLALWGMVVGDKLLVVPQDGSHWLSMKDIVEVLSDRGHEIVVVV
PEVNLLLKESKYYTRKIYPVPYDQEELKNRYQSFGNNHFAERSFLTAPQTEYRNNMIVIG
LYFINCQSLLQDRDTLNFFKESKFDALFTDPALPCGVILAEYLGLPSVYLFRGFPCSLEH
TFSRSPDPVSYIPRCYTKFSDHMTFSQRVANFLVNLLEPYLFYCLFSKYEELASAVLKRD
VDIITLYQKVSVWLLRYDFVLEYPRPVMPNMVFIGGINCKKRKDLSQEFEAYINASGEHG
IVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLL
GHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSE
DLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDL
TWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues
532
Molecular Weight
60750.215
Theoretical pI
Not Available
GO Classification
Functions
enzyme binding / glucuronosyltransferase activity / protein heterodimerization activity / protein homodimerization activity
Processes
cellular glucuronidation / cellular response to hormone stimulus / flavonoid biosynthetic process / flavonoid glucuronidation / negative regulation of cellular glucuronidation / negative regulation of fatty acid metabolic process / negative regulation of glucuronosyltransferase activity / small molecule metabolic process / xenobiotic glucuronidation / xenobiotic metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / extracellular exosome / integral component of membrane
General Function
Protein homodimerization activity
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 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).
Pfam Domain Function
Transmembrane Regions
490-506
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0020785|UDP-glucuronosyltransferase 1-6 (UGT1A6)
ATGGCCTGCCTCCTTCGCTCATTTCAGAGAATTTCTGCAGGGGTTTTCTTCTTAGCACTT
TGGGGCATGGTTGTAGGTGACAAGCTGCTGGTGGTCCCTCAGGACGGAAGCCACTGGCTT
AGTATGAAGGATATAGTTGAGGTTCTCAGTGACCGGGGTCATGAGATTGTAGTGGTGGTG
CCTGAAGTTAATTTGCTTTTGAAAGAATCCAAATACTACACAAGAAAAATCTATCCAGTG
CCGTATGACCAAGAAGAGCTGAAGAACCGTTACCAATCATTTGGAAACAATCACTTTGCT
GAGCGATCATTCCTAACTGCTCCTCAGACAGAGTACAGGAATAACATGATTGTTATTGGC
CTGTACTTCATCAACTGCCAGAGCCTCCTGCAGGACAGGGACACCCTGAACTTCTTTAAG
GAGAGCAAGTTTGATGCTCTTTTCACAGACCCAGCCTTACCCTGTGGGGTGATCCTGGCT
GAGTATTTGGGCCTACCATCTGTGTACCTCTTCAGGGGTTTTCCGTGTTCCCTGGAGCAT
ACATTCAGCAGAAGCCCAGACCCTGTGTCCTACATTCCCAGGTGCTACACAAAGTTTTCA
GACCACATGACTTTTTCCCAACGAGTGGCCAACTTCCTTGTTAATTTGTTGGAGCCCTAT
CTATTTTATTGTCTGTTTTCAAAGTATGAAGAACTCGCATCAGCTGTCCTCAAGAGAGAT
GTGGATATAATCACCTTATATCAGAAGGTCTCTGTTTGGCTGTTAAGATATGACTTTGTG
CTTGAATATCCTAGGCCGGTCATGCCCAACATGGTCTTCATTGGAGGTATCAACTGTAAG
AAGAGGAAAGACTTGTCTCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAACATGGA
ATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCTATGGCA
ATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGAACCCGA
CCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGATCTGCTT
GGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTATGAAAGC
ATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGACAATGCA
AAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACTTCTGAA
GATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAACATCATG
CGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTGTTCTGG
GTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCACGACCTC
ACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTGCTGACA
GTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGGAAAAAA
GGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Chromosome Location
2
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP19224
UniProtKB Entry NameUD16_HUMAN
HGNC IDHGNC:12538
General 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. [PubMed:1339448]
  2. Harding D, Fournel-Gigleux S, Jackson MR, Burchell B: Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8381-5. [PubMed:3141926]
  3. 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]
  4. 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]
  5. 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]
  6. Munzel PA, Lehmkoster T, Bruck M, Ritter JK, Bock KW: Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6. Arch Biochem Biophys. 1998 Feb 1;350(1):72-8. [PubMed:9466822]
  7. 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]
  8. 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]
  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. Ciotti M, Marrone A, Potter C, Owens IS: Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics. 1997 Dec;7(6):485-95. [PubMed:9429234]
  11. Nagar S, Zalatoris JJ, Blanchard RL: Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics. 2004 Aug;14(8):487-99. [PubMed:15284531]
  12. 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
DB00197Troglitazoneapproved, investigational, withdrawnunknownsubstrateinhibitorDetails
DB00688Mycophenolate mofetilapproved, investigationalunknownsubstrateDetails
DB00818Propofolapproved, investigational, vet_approvedunknownsubstrateDetails
DB01024Mycophenolic acidapprovedunknownsubstrateDetails
DB08826DeferiproneapprovedunknownsubstrateDetails
DB00316AcetaminophenapprovedunknownsubstrateDetails
DB00313Valproic acidapproved, investigationalunknownsubstrateDetails
DB01320Fosphenytoinapproved, investigationalnoinhibitorDetails
DB00252Phenytoinapproved, vet_approvednoinhibitorDetails
DB09288PropacetamolexperimentalnosubstrateDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownsubstrateDetails
DB00788Naproxenapproved, vet_approvedunknownsubstrateDetails
DB00564Carbamazepineapproved, investigationalunknowninducerDetails
DB14635Curcumin sulfateexperimentalunknowninhibitorDetails