UDP-glucuronosyltransferase 1-4

Details

Name
UDP-glucuronosyltransferase 1-4
Synonyms
  • 2.4.1.17
  • Bilirubin-specific UDPGT isozyme 2
  • GNT1
  • hUG-BR2
  • UDP-glucuronosyltransferase 1-D
  • UDP-glucuronosyltransferase 1A4
  • UDPGT 1-4
  • UGT-1D
  • UGT1
  • UGT1D
Gene Name
UGT1A4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006829|UDP-glucuronosyltransferase 1-4
MARGLQVPLPRLATGLLLLLSVQPWAESGKVLVVPTDGSPWLSMREALRELHARGHQAVV
LTPEVNMHIKEEKFFTLTAYAVPWTQKEFDRVTLGYTQGFFETEHLLKRYSRSMAIMNNV
SLALHRCCVELLHNEALIRHLNATSFDVVLTDPVNLCGAVLAKYLSIPAVFFWRYIPCDL
DFKGTQCPNPSSYIPKLLTTNSDHMTFLQRVKNMLYPLALSYICHTFSAPYASLASELFQ
REVSVVDLVSYASVWLFRGDFVMDYPRPIMPNMVFIGGINCANGKPLSQEFEAYINASGE
HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Number of residues
534
Molecular Weight
60024.535
Theoretical pI
8.68
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 / heme catabolic process / negative regulation of cellular glucuronidation / negative regulation of fatty acid metabolic process / negative regulation of glucuronosyltransferase activity / porphyrin-containing compound metabolic process / small molecule metabolic process / xenobiotic glucuronidation / xenobiotic metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / 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 glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).
Pfam Domain Function
Transmembrane Regions
492-508
Cellular Location
Microsome
Gene sequence
>lcl|BSEQ0012467|UDP-glucuronosyltransferase 1-4 (UGT1A4)
ATGGCCAGAGGACTCCAGGTTCCCCTGCCGCGGCTGGCCACAGGACTGCTGCTCCTCCTC
AGTGTCCAGCCCTGGGCTGAGAGTGGAAAGGTGTTGGTGGTGCCCACTGATGGCAGCCCC
TGGCTCAGCATGCGGGAGGCCTTGCGGGAGCTCCATGCCAGAGGCCACCAGGCGGTGGTC
CTCACCCCAGAGGTGAATATGCACATCAAAGAAGAGAAATTTTTCACCCTGACAGCCTAT
GCTGTTCCATGGACCCAGAAGGAATTTGATCGCGTTACGCTGGGCTACACTCAAGGGTTC
TTTGAAACAGAACATCTTCTGAAGAGATATTCTAGAAGTATGGCAATTATGAACAATGTA
TCTTTGGCCCTTCATAGGTGTTGTGTGGAGCTACTGCATAATGAGGCCCTGATCAGGCAC
CTGAATGCTACTTCCTTTGATGTGGTTTTAACAGACCCCGTTAACCTCTGTGGGGCGGTG
CTGGCTAAGTACCTGTCGATTCCTGCTGTGTTTTTTTGGAGGTACATTCCATGTGACTTA
GACTTTAAGGGCACACAGTGTCCAAATCCTTCCTCCTATATTCCTAAGTTACTAACGACC
AATTCAGACCACATGACATTCCTGCAAAGGGTCAAGAACATGCTCTACCCTCTGGCCCTG
TCCTACATTTGCCATACTTTTTCTGCCCCTTATGCAAGTCTTGCCTCTGAGCTTTTTCAG
AGAGAGGTGTCAGTGGTGGATCTTGTCAGCTATGCATCCGTGTGGCTGTTCCGAGGGGAC
TTTGTGATGGACTACCCCAGGCCGATCATGCCCAACATGGTCTTCATTGGGGGCATCAAC
TGTGCCAACGGGAAGCCACTATCTCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAA
CATGGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCT
ATGGCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGA
ACCCGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGAT
CTGCTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTAT
GAAAGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGAC
AATGCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACT
TCTGAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAAC
ATCATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTG
TTCTGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCAC
GACCTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTG
CTGACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGG
AAAAAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Chromosome Location
2
Locus
2q37
External Identifiers
ResourceLink
UniProtKB IDP22310
UniProtKB Entry NameUD14_HUMAN
GenBank Protein ID184475
GenBank Gene IDM57951
HGNC IDHGNC:12536
General References
  1. 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. [Article]
  2. 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. [Article]
  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. [Article]
  4. Zhang T, Haws P, Wu Q: Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. Genome Res. 2004 Jan;14(1):79-89. Epub 2003 Dec 12. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  7. 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. [Article]
  8. Hsieh TY, Shiu TY, Huang SM, Lin HH, Lee TC, Chen PJ, Chu HC, Chang WK, Jeng KS, Lai MM, Chao YC: Molecular pathogenesis of Gilbert's syndrome: decreased TATA-binding protein binding affinity of UGT1A1 gene promoter. Pharmacogenet Genomics. 2007 Apr;17(4):229-36. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. 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. [Article]
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  13. Bosma PJ, Chowdhury JR, Huang TJ, Lahiri P, Elferink RP, Van Es HH, Lederstein M, Whitington PF, Jansen PL, Chowdhury NR: Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I. FASEB J. 1992 Jul;6(10):2859-63. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00910Paricalcitolapproved, investigationalunknownsubstrateDetails
DB00831Trifluoperazineapproved, investigationalunknownsubstrateDetails
DB00363ClozapineapprovednosubstrateDetails
DB00197Troglitazoneapproved, investigational, withdrawnunknownsubstrateDetails
DB04953Ezogabineapproved, investigationalunknownsubstrateDetails
DB06216AsenapineapprovedunknownsubstrateDetails
DB00683Midazolamapproved, illicitnosubstrateDetails
DB00313Valproic acidapproved, investigationalunknownsubstrateDetails
DB06401Bazedoxifeneapproved, investigationalunknownsubstrateDetails
DB09262ImidafenacininvestigationalnosubstrateDetails
DB13874Enasidenibapproved, investigationalunknownsubstrateDetails
DB11827Ertugliflozinapproved, investigationalnoinhibitorDetails
DB12020Tecovirimatapproved, investigationalunknownsubstrateDetails
DB00334Olanzapineapproved, investigationalnosubstrateDetails
DB12978Pexidartinibapproved, investigationalunknownsubstrateDetails
DB00924CyclobenzaprineapprovedunknownsubstrateDetails
DB01217Anastrozoleapproved, investigationalunknownsubstrateDetails
DB00321AmitriptylineapprovedunknownsubstrateDetails
DB06077Lumateperoneapproved, investigationalnosubstrateDetails
DB00252Phenytoinapproved, vet_approvednosubstrateDetails
DB00977EthinylestradiolapprovedunknownsubstrateDetails
DB09054IdelalisibapprovedunknownsubstrateinhibitorDetails
DB11837Osilodrostatapproved, investigationalunknownsubstrateDetails
DB09241Methylene blueapproved, investigationalunknowninhibitorDetails
DB00920KetotifenapprovedunknownsubstrateDetails
DB00434CyproheptadineapprovedunknownsubstrateDetails
DB08804Nandrolone decanoateapproved, illicitunknownsubstrateDetails
DB00349Clobazamapproved, illicitnoinhibitorDetails
DB00555Lamotrigineapproved, investigationalunknownsubstrateDetails
DB00503Ritonavirapproved, investigationalnoinducerDetails
DB14635Curcumin sulfateexperimentalunknowninhibitorDetails
DB00794Primidoneapproved, vet_approvedunknowninducerDetails
DB00783Estradiolapproved, investigational, vet_approvedunknownsubstrateinducerDetails
DB00714Apomorphineapproved, investigationalunknownsubstrateDetails
DB11796Fostemsavirapproved, investigationalunknownsubstrateDetails
DB00871TerbutalineapprovedunknownsubstrateDetails
DB00960Pindololapproved, investigationalunknownsubstrateDetails
DB12471Ibrexafungerpapproved, investigationalunknownsubstrateDetails