UDP-glucuronosyltransferase 1-3

Details

Name
UDP-glucuronosyltransferase 1-3
Synonyms
  • 2.4.1.17
  • GNT1
  • UDP-glucuronosyltransferase 1-C
  • UDP-glucuronosyltransferase 1A3
  • UDPGT 1-3
  • UGT-1C
  • UGT1
  • UGT1C
Gene Name
UGT1A3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007065|UDP-glucuronosyltransferase 1-3
MATGLQVPLPWLATGLLLLLSVQPWAESGKVLVVPIDGSHWLSMREVLRELHARGHQAVV
LTPEVNMHIKEENFFTLTTYAISWTQDEFDRHVLGHTQLYFETEHFLKKFFRSMAMLNNM
SLVYHRSCVELLHNEALIRHLNATSFDVVLTDPVNLCAAVLAKYLSIPTVFFLRNIPCDL
DFKGTQCPNPSSYIPRLLTTNSDHMTFMQRVKNMLYPLALSYICHAFSAPYASLASELFQ
REVSVVDILSHASVWLFRGDFVMDYPRPIMPNMVFIGGINCANRKPLSQEFEAYINASGE
HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues
534
Molecular Weight
60337.835
Theoretical pI
8.28
GO Classification
Functions
enzyme binding / glucuronosyltransferase activity / protein heterodimerization activity / protein homodimerization activity / retinoic acid binding
Processes
cellular glucuronidation / cellular response to hormone stimulus / 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 / xenobiotic glucuronidation
Components
endoplasmic reticulum / endoplasmic reticulum membrane / 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. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Pfam Domain Function
Transmembrane Regions
492-508
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0017182|UDP-glucuronosyltransferase 1-3 (UGT1A3)
ATGGCCACAGGACTCCAGGTTCCCCTGCCGTGGCTGGCCACAGGACTGCTGCTTCTCCTC
AGTGTCCAGCCCTGGGCTGAGAGTGGAAAGGTGTTGGTGGTGCCCATTGATGGCAGCCAC
TGGCTCAGCATGCGGGAGGTCTTGCGGGAGCTCCATGCCAGAGGCCACCAGGCAGTGGTC
CTCACCCCAGAGGTGAATATGCACATCAAAGAAGAGAACTTTTTCACCCTGACAACCTAT
GCCATTTCGTGGACCCAGGATGAATTTGATCGCCATGTGCTGGGCCACACTCAACTGTAC
TTTGAAACAGAACATTTTCTGAAGAAATTTTTCAGAAGTATGGCAATGTTGAACAATATG
TCTTTGGTCTATCATAGGTCTTGTGTGGAGCTACTACATAATGAGGCCCTGATCAGGCAC
CTGAATGCTACTTCCTTTGATGTGGTTTTAACAGACCCCGTTAACCTCTGCGCGGCAGTG
CTGGCTAAGTACCTGTCGATTCCTACTGTGTTTTTTTTGAGGAACATTCCATGTGATTTA
GACTTTAAGGGCACACAGTGTCCAAACCCTTCCTCCTATATTCCTAGATTACTAACAACC
AATTCAGACCACATGACATTCATGCAAAGGGTCAAGAACATGCTCTACCCTCTGGCCCTG
TCCTACATTTGCCATGCTTTTTCTGCTCCTTATGCAAGCCTTGCCTCTGAGCTTTTTCAG
AGAGAGGTGTCAGTGGTGGATATTCTCAGTCATGCATCTGTGTGGCTGTTCCGAGGGGAC
TTTGTGATGGACTACCCCAGGCCAATCATGCCCAACATGGTCTTCATTGGGGGCATCAAC
TGTGCCAACAGGAAGCCACTATCTCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAA
CATGGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCT
ATGGCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGA
ACCCGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGAT
CTGCTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTAT
GAAAGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGAC
AATGCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACT
TCTGAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAAC
ATCATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTG
TTCTGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCAC
GACCTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTG
CTGACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGG
AAAAAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Chromosome Location
2
Locus
2q37
External Identifiers
ResourceLink
UniProtKB IDP35503
UniProtKB Entry NameUD13_HUMAN
GenBank Protein ID340135
GenBank Gene IDM84127
HGNC IDHGNC:12535
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. 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. Alonen A, Finel M, Kostiainen R: The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72. doi: 10.1016/j.bcp.2008.07.006. Epub 2008 Jul 12. [PubMed:18674515]
  5. 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]
  6. 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]
  7. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  8. 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
DB00796Candesartan cilexetilapprovedunknownsubstrateDetails
DB01029Irbesartanapproved, investigationalunknownsubstrateDetails
DB00678LosartanapprovedunknownsubstrateDetails
DB00749Etodolacapproved, investigational, vet_approvedunknownsubstrateDetails
DB00712Flurbiprofenapproved, investigationalunknownsubstrateDetails
DB01050IbuprofenapprovedunknownsubstrateDetails
DB00327Hydromorphoneapproved, illicitnosubstrateDetails
DB01252MitiglinideinvestigationalunknownsubstrateDetails
DB04725LicofeloneinvestigationalunknownsubstrateDetails
DB06741GavestinelinvestigationalunknownsubstrateDetails
DB06210EltrombopagapprovedunknownsubstrateDetails
DB06403Ambrisentanapproved, investigationalunknownsubstrateDetails
DB00197Troglitazoneinvestigational, withdrawnunknownsubstrateDetails
DB00295Morphineapproved, investigationalnosubstrateDetails
DB00555Lamotrigineapproved, investigationalunknownsubstrateDetails
DB00973EzetimibeapprovedunknownsubstrateDetails
DB06510MuraglitazarinvestigationalunknownsubstrateDetails
DB00434CyproheptadineapprovedunknownsubstrateDetails
DB04953Ezogabineapproved, investigationalunknownsubstrateDetails
DB08860PitavastatinapprovedunknownsubstrateDetails
DB01076AtorvastatinapprovednosubstrateDetails
DB00227Lovastatinapproved, investigationalunknownsubstrateDetails
DB00641SimvastatinapprovedunknownsubstrateDetails
DB01544Flunitrazepamapproved, illicitunknowninhibitorDetails
DB01095FluvastatinapprovedunknownsubstrateDetails
DB00313Valproic Acidapproved, investigationalunknownsubstrateDetails
DB11943Delafloxacinapproved, investigationalnosubstrateDetails
DB11691Naldemedineapproved, investigationalnosubstrateDetails
DB13874Enasidenibapproved, investigationalunknownsubstrateDetails
DB13919CandesartanexperimentalunknownsubstrateDetails
DB12070Letermovirapproved, investigationalnosubstrateDetails
DB06230Nalmefeneapproved, investigational, withdrawnnosubstrateDetails
DB08930DolutegravirapprovednosubstrateDetails
DB05928DovitinibinvestigationalunknowninhibitorDetails
DB01609Deferasiroxapproved, investigationalunknowninhibitorDetails
DB09213Dexibuprofenapproved, investigationalunknownDetails
DB13997Baloxavir marboxilapproved, investigationalunknownsubstrateDetails
DB00966Telmisartanapproved, investigationalunknownsubstrateDetails
DB01241GemfibrozilapprovedunknowninhibitorDetails
DB12130Lorlatinibapproved, investigationalunknownsubstrateDetails