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Identification
HMDB Protein ID HMDBP00478
Secondary Accession Numbers
  • 5719
Name UDP-glucuronosyltransferase 1-4
Synonyms
  1. Bilirubin-specific UDPGT isozyme 2
  2. UDP-glucuronosyltransferase 1-D
  3. UDP-glucuronosyltransferase 1A4
  4. UDPGT 1-4
  5. UGT-1D
  6. UGT1*4
  7. UGT1-04
  8. UGT1.4
  9. UGT1D
  10. hUG-BR2
Gene Name UGT1A4
Protein Type Enzyme
Biological Properties
General Function Involved in transferase activity, transferring hexosyl groups
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.
Pathways
  • Ascorbate and aldarate metabolism
  • Chemical carcinogenesis - DNA adducts
  • Drug metabolism - cytochrome P450
  • Drug metabolism - other enzymes
  • Metabolism of xenobiotics by cytochrome P450
  • Nicotine Action Pathway
  • Nicotine Metabolism Pathway
  • Pentose and glucuronate interconversions
  • Phenytoin (Antiarrhythmic) Action Pathway
  • Porphyrin and chlorophyll metabolism
  • Retinol metabolism
  • Starch and sucrose metabolism
  • Steroid hormone biosynthesis
  • Tamoxifen Action Pathway
  • Tamoxifen Metabolism Pathway
Reactions
Uridine diphosphate glucuronic acid + acceptor → Uridine 5'-diphosphate + acceptor beta-D-glucuronoside details
Uridine diphosphate glucuronic acid + ROH → Uridine 5'-diphosphate + beta-D-Glucuronoside details
Estrone + Uridine diphosphate glucuronic acid → Estrone glucuronide + Uridine 5'-diphosphate details
Uridine diphosphate glucuronic acid + Bilirubin → Uridine 5'-diphosphate + Bilirubin diglucuronide details
Androsterone + Uridine diphosphate glucuronic acid → Androsterone glucuronide + Uridine 5'-diphosphate details
Testosterone + Uridine diphosphate glucuronic acid → Testosterone glucuronide + Uridine 5'-diphosphate details
all-trans-Retinoic acid + Uridine diphosphate glucuronic acid → Retinoyl b-glucuronide + Uridine 5'-diphosphate details
Estradiol + Uridine diphosphate glucuronic acid → 17-beta-Estradiol-3-glucuronide + Uridine 5'-diphosphate details
Etiocholanolone + Uridine diphosphate glucuronic acid → Etiocholanolone glucuronide + Uridine 5'-diphosphate details
2-Methoxyestrone + Uridine diphosphate glucuronic acid → 2-Methoxyestrone 3-glucuronide + Uridine 5'-diphosphate details
2-Methoxyestradiol + Uridine diphosphate glucuronic acid → 2-Methoxy-estradiol-17b 3-glucuronide + Uridine 5'-diphosphate details
Uridine diphosphate glucuronic acid + Estriol → Uridine 5'-diphosphate + Estriol-16-Glucuronide details
2,2,2-Trichloroethanol + Uridine diphosphate glucuronic acid → Trichloroethanol glucuronide + Uridine 5'-diphosphate details
SN-38 + Uridine diphosphate glucuronic acid → SN38 glucuronide + Uridine 5'-diphosphate details
Uridine diphosphate glucuronic acid + Codeine → Uridine 5'-diphosphate + Codeine-6-glucuronide details
Morphine + Uridine diphosphate glucuronic acid → Morphine-3-glucuronide + Uridine 5'-diphosphate details
Morphine + Uridine diphosphate glucuronic acid → Morphine-6-glucuronide + Uridine 5'-diphosphate details
Uridine diphosphate glucuronic acid + Water → Uridine 5'-diphosphate + D-Glucuronic acid details
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + Uridine diphosphate glucuronic acid → 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide + Uridine 5'-diphosphate details
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + Uridine diphosphate glucuronic acid → NNAL-N-glucuronide + Uridine 5'-diphosphate details
Uridine diphosphate glucuronic acid + Acceptor → Uridine 5'-diphosphate + Acceptor beta-D-glucuronoside details
GO Classification
Biological Process
small molecule metabolic process
xenobiotic metabolic process
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Function
catalytic activity
transferase activity
transferase activity, transferring hexosyl groups
transferase activity, transferring glycosyl groups
Molecular Function
glucuronosyltransferase activity
enzyme binding
Process
metabolic process
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Microsome
  3. Single-pass membrane protein (Potential)
Gene Properties
Chromosome Location 2
Locus 2q37
SNPs UGT1A4
Gene Sequence
>1605 bp
ATGGCCAGAGGACTCCAGGTTCCCCTGCCGCGGCTGGCCACAGGACTGCTGCTCCTCCTC
AGTGTCCAGCCCTGGGCTGAGAGTGGAAAGGTGTTGGTGGTGCCCACTGATGGCAGCCCC
TGGCTCAGCATGCGGGAGGCCTTGCGGGAGCTCCATGCCAGAGGCCACCAGGCGGTGGTC
CTCACCCCAGAGGTGAATATGCACATCAAAGAAGAGAAATTTTTCACCCTGACAGCCTAT
GCTGTTCCATGGACCCAGAAGGAATTTGATCGCGTTACGCTGGGCTACACTCAAGGGTTC
TTTGAAACAGAACATCTTCTGAAGAGATATTCTAGAAGTATGGCAATTATGAACAATGTA
TCTTTGGCCCTTCATAGGTGTTGTGTGGAGCTACTGCATAATGAGGCCCTGATCAGGCAC
CTGAATGCTACTTCCTTTGATGTGGTTTTAACAGACCCCGTTAACCTCTGCGGGGCGGTG
CTGGCTAAGTACCTGTCGATTCCTGCTGTGTTTTTTTGGAGGTACATTCCATGTGACTTA
GACTTTAAGGGCACACAGTGTCCAAATCCTTCCTCCTATATTCCTAAGTTACTAACGACC
AATTCAGACCACATGACATTCCTGCAAAGGGTCAAGAACATGCTCTACCCTCTGGCCCTG
TCCTACATTTGCCATACTTTTTCTGCCCCTTATGCAAGTCTTGCCTCTGAGCTTTTTCAG
AGAGAGGTGTCAGTGGTGGATCTTGTCAGCTATGCATCCGTGTGGCTGTTCCGAGGGGAC
TTTGTGATGGACTACCCCAGGCCGATCATGCCCAACATGGTCTTCATTGGGGGCATCAAC
TGTGCCAACGGGAAGCCACTATCTCAGGAATTTGAAGCCTACATTAATGCTTCTGGAGAA
CATGGAATTGTGGTTTTCTCTTTGGGATCAATGGTCTCAGAAATTCCAGAGAAGAAAGCT
ATGGCAATTGCTGATGCTTTGGGCAAAATCCCTCAGACAGTCCTGTGGCGGTACACTGGA
ACCCGACCATCGAATCTTGCGAACAACACGATACTTGTTAAGTGGCTACCCCAAAACGAT
CTGCTTGGTCACCCGATGACCCGTGCCTTTATCACCCATGCTGGTTCCCATGGTGTTTAT
GAAAGCATATGCAATGGCGTTCCCATGGTGATGATGCCCTTGTTTGGTGATCAGATGGAC
AATGCAAAGCGCATGGAGACTAAGGGAGCTGGAGTGACCCTGAATGTTCTGGAAATGACT
TCTGAAGATTTAGAAAATGCTCTAAAAGCAGTCATCAATGACAAAAGTTACAAGGAGAAC
ATCATGCGCCTCTCCAGCCTTCACAAGGACCGCCCGGTGGAGCCGCTGGACCTGGCCGTG
TTCTGGGTGGAGTTTGTGATGAGGCACAAGGGCGCGCCACACCTGCGCCCCGCAGCCCAC
GACCTCACCTGGTACCAGTACCATTCCTTGGACGTGATTGGTTTCCTCTTGGCCGTCGTG
CTGACAGTGGCCTTCATCACCTTTAAATGTTGTGCTTATGGCTACCGGAAATGCTTGGGG
AAAAAAGGGCGAGTTAAGAAAGCCCACAAATCCAAGACCCATTGA
Protein Properties
Number of Residues 534
Molecular Weight 60024.535
Theoretical pI 8.543
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>UDP-glucuronosyltransferase 1-4
MARGLQVPLPRLATGLLLLLSVQPWAESGKVLVVPTDGSPWLSMREALRELHARGHQAVV
LTPEVNMHIKEEKFFTLTAYAVPWTQKEFDRVTLGYTQGFFETEHLLKRYSRSMAIMNNV
SLALHRCCVELLHNEALIRHLNATSFDVVLTDPVNLCGAVLAKYLSIPAVFFWRYIPCDL
DFKGTQCPNPSSYIPKLLTTNSDHMTFLQRVKNMLYPLALSYICHTFSAPYASLASELFQ
REVSVVDLVSYASVWLFRGDFVMDYPRPIMPNMVFIGGINCANGKPLSQEFEAYINASGE
HGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQND
LLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMT
SEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAH
DLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P22310
UniProtKB/Swiss-Prot Entry Name UD14_HUMAN
PDB IDs Not Available
GenBank Gene ID M57951
GeneCard ID UGT1A4
GenAtlas ID UGT1A4
HGNC ID HGNC:12536
References
General References
  1. 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 ]
  2. 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. [PubMed:14702039 ]
  3. 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. [PubMed:1898728 ]
  4. 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 ]
  5. 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 ]
  6. 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. [PubMed:1634050 ]
  7. 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. [PubMed:8280139 ]
  8. 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. [PubMed:8276413 ]
  9. 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 ]