Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

2.4.1.17

Official Name

glucuronosyltransferase

Name from literature

bilirubin uridine diphosphate glucuronosyltransferase

Pathway from literature

the conjugation of bilirubin with glucuronic acid in its excretion process into the bile

Pathway from KEGG

Lipid Metabolism; Androgen and estrogen metabolism; map00150

Xenobiotics Biodegradation and Metabolism; Metabolism of xenobiotics by cytochrome P450; map00980

Metabolism of Cofactors and Vitamins; Retinol metabolism; map00830

Metabolism of Cofactors and Vitamins; Porphyrin and chlorophyll metabolism; map00860

Carbohydrate Metabolism; Starch and sucrose metabolism; map00500

Carbohydrate Metabolism; Pentose and glucuronate interconversions; map00040

Xenobiotics Biodegradation and Metabolism; Drug metabolism - cytochrome P450; map00982

Xenobiotics Biodegradation and Metabolism; Drug metabolism - other enzymes; map00983

Organisms

Human (9606)

Genome localization

2q37[54658 ], 4q13[7367 ], 2q37[54575 ], 4q13[10941 ], 4q13[7363 ], 2q37[54600 ], 4q13.2[54490 ], 4q13.2[79799 ], 2q37[54657 ], 2q37[54578 ], 2q37[54576 ], 2q37[54579 ], 4q13.2[7365 ], 4q13[7366 ], 4q13.2[10720 ], 4q13[7364 ], 2q37[54577 ], 2q37[54659 ],

Comments

This entry denotes a family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines and fatty acids. Some of the activities catalysed were previously listed separately as EC 2.4.1.42, EC 2.4.1.59, EC 2.4.1.61, EC 2.4.1.76, EC 2.4.1.77, EC 2.4.1.84, EC 2.4.1.107 and EC 2.4.1.108. A temporary nomenclature for the various forms, whose delineation is in a state of flux, is suggested in Ref. 1.

Rate-limiting Description

"Bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) is the rate-limiting enzyme for the conjugation of bilirubin with glucuronic acid in its excretion process into the bile." (16623861)

Regulatory Information

Upstream transcription factor

5578;3172;6927

Regulatory type

Detail

key enzyme;

"Glucuronyltransferase-I (GlcAT-I) is the key enzyme that completes the synthesis of this linkage region, which is a prerequisite for the conversion of core proteins to functional proteoglycans bearing GAGs." (18400750)

phosphorylation;PKC(5578)

"UDP-glucuronosyltransferase chemical detoxifying system requires regulated phosphorylation supported by protein kinase C" (18556656)

transcriptional factor;hepatocyte nuclear factor 4alpha(3172)

"the human UDP-glucuronosyltransferase 1A9 promoter can indeed be upregulated by human hepatocyte nuclear factor 4alpha in vitro" (17264800)

transcriptional factor;HNF1alpha(6927)

"Provide evidence for HNF1alpha as a determinant of UGT1A9 mRNA expression, but suggest a role for multiple transcription factors." (17440429)

phosphorylation;

"human bilirubin UDP-glucuronosyltransferase requires phosphorylation for activity" (12646172)

transcriptional factor;HNF1alpha(6927)

"Provide evidence for HNF1alpha as a determinant of UGT1A1 mRNA expression, but suggest a role for multiple transcription factors." (17440429)

transcriptional factor;HNF1alpha(6927)

"Provide evidence for HNF1alpha as a determinant of UGT2B7 mRNA expression, but suggest a role for multiple transcription factors." (17440429)

phosphorylation;

P35503

phosphorylation;

Q9HAW7

phosphorylation;

Q9HAW8

Gene ontology

Gene ontology

GO:0006789 (P) bilirubin conjugation [P22309 ];
GO:0008202 (P) steroid metabolic process [P54855, O75795 ];
GO:0008210 (P) estrogen metabolic process [P22309, O75310 ];
GO:0006629 (P) lipid metabolic process [P36537, P16662 ];
GO:0006805 (P) xenobiotic metabolic process [P19224, O75310, P54855, Q9BY64, P35504, P06133, O60656 ];
GO:0015020 (F) glucuronosyltransferase activity [Q5QTE2, P22310, Q9HAW7, Q4R0Z5, O75310, Q5QTD9, P54855, Q5QTE5, Q5K673, Q9HAW8, P22309, P06133, Q4R0Z7, Q9HAW9, Q5K672, Q5K674, O75795, Q3SY77, P16662, P35504, Q5K632, Q4R0Z6, Q5QTE3, Q5QTE4, Q5QTE0, Q6UWM9, P19224, Q6NUS8, P36537, Q9BY64, P35503, Q9Y4X1, O60656, Q5QTE1 ];
GO:0009593 (P) detection of chemical stimulus [Q9Y4X1 ];
GO:0005789 (C) endoplasmic reticulum membrane [P16662, P35504, P22310, Q9HAW7, O75310, P54855, P19224, Q9HAW8, P22309, P36537, P06133, Q9BY64, P35503, Q9HAW9, O60656, O75795 ];
GO:0016021 (C) integral to membrane [P16662, P35504, P22310, Q9HAW7, O75310, P54855, Q6UWM9, Q9HAW8, P19224, Q6NUS8, P36537, P06133, Q9BY64, P35503, Q9Y4X1, Q9HAW9, O60656, O75795, Q3SY77 ];
GO:0007586 (P) digestion [P22309 ];
GO:0005792 (C) microsome [P16662, P35504, P22310, Q9HAW7, O75310, P54855, P19224, Q9HAW8, P22309, P36537, P06133, Q9BY64, P35503, Q9HAW9, O60656, O75795 ];
GO:0006711 (P) estrogen catabolic process [P06133 ];
GO:0007608 (P) sensory perception of smell [Q9Y4X1 ];
GO:0008152 (P) metabolic process [Q5QTE2, P22310, Q9HAW7, Q5K632, Q5QTE3, Q4R0Z6, Q5QTE4, Q5QTE0, Q4R0Z5, Q5QTD9, Q6UWM9, Q5QTE5, Q5K673, Q9HAW8, Q6NUS8, P35503, Q4R0Z7, Q9Y4X1, Q9HAW9, Q5K672, Q3SY77, Q5K674, Q5QTE1 ];

Tissue expression

Tissue From HPRD

Biliary apparatus [08402, 07566, 07336 ];
Colon [08402, 07566, 07336, 07072 ];
Jejunum [08933, 07566, 07336, 07072 ];
Larynx [09397 ];
Fetus [05279 ];
Oesophagus epithelium [07193, 02508 ];
Macrophage [07073 ];
Hepatocyte [02508 ];
Testis [07073, 05931, 07192, 03545, 02507 ];
Tonsil [07336, 09397 ];
Tongue [07336, 09397 ];
Brain [05279 ];
Spleen [05931 ];
Small intestine [07073, 08933, 07566, 05931, 07336, 07192, 07072 ];
Adipose tissue [07192, 04345, 02507 ];
Cerebellum [02508 ];
Duodenum [08933, 07566, 02508, 07336, 02507 ];
Uterus [07192, 03545 ];
Large intestine [07336 ];
Intestine [08402 ];
Oesophagus [07336, 07192, 09397 ];
Liver [08402, 08933, 05931, 07336, 07192, 04345, 03545, 02507, 07193, 07071, 07073, 07566, 02508 ];
Olfactory system [05279 ];
Skeletal muscle [07073, 05931 ];
Prostate [07073, 05931, 07192, 04345, 03545, 02507 ];
Kidney [05931, 07192, 04345, 03545, 02507, 07071, 07073, 02508 ];
Mammary gland [07073, 08933, 05931, 07192, 04345, 03545, 02507 ];
Adrenal gland [04345, 03545, 02507 ];
Bile duct [08933 ];
Oral mucosa [09397 ];
Lung [05931, 02508, 07192, 04345, 03545, 09397, 02507 ];
Pancreas [02508 ];
Skin [07073, 07071, 07192, 04345, 02507 ];
Ileum [07193, 08933, 07566, 07336, 07072 ];
Ovary [07073 ];
Placenta [05931, 07192, 03545, 02507 ];
Stomach [07073, 07566, 05931, 07336, 09397 ];

Tissue specificity

Expressed in many tissues. Present in liver, prostate and testis [P54855 ];

Liver and colon [Q9HAW8 ];

Expressed in the liver, breast and kidney [Q9BY64 ];

Olfactory epithelium and brain [Q9Y4X1 ];

Colon specific [Q9HAW9 ];

Liver and gastric tissue [Q9HAW7 ];

Expressed in various tissues including the liver, kidney, testis, uterus, placenta, mammary gland, adrenal gland, skin and prostate [O75795 ];

Liver [O60656 ];

Widely expressed [O75310 ];

Expressed in skin, kidney and liver [P19224 ];

Expressed in liver. Not expressed in skin or kidney [P22309, P22310 ];

Subcellular localization

Localization

cell membrane [Q6NUS8, Q9Y4X1, Q6UWM9, Q3SY77 ];

endoplasmic reticulum [P16662, P35504, P22310, Q9HAW7, O75310, P54855, P19224, Q9HAW8, P22309, P36537, P06133, Q9BY64, P35503, Q9HAW9, O60656, O75795 ];

microsome [P16662, P35504, P22310, Q9HAW7, O75310, P54855, P19224, Q9HAW8, P22309, P36537, P06133, Q9BY64, P35503, Q9HAW9, O60656, O75795 ];

Disease relevance

Disease

The Gilbert syndrome is shown to occur as a consequence of reduced bilirubin transferase activity. The disorder, is most often detected in young adults with vague nonspecific complaints. A more severe inheritable deficiency in bilirubin activity exist in Crigler-Najjar (CN): patients with type I (recessive trait) have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. Patients with type II (dominant trait) have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice [P22310 ];

Defects in UGT1A1 may be a cause of transient familial neonatal hyperbilirubinemia [MIM:237900]. The defects is characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants. It has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unclear. Defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. Mutations are identical to those detected in patients with Gilbert syndrome [MIM:143500], a risk factor of neonatal non-physiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia [P22309 ];

Defects in UGT1A1 are the cause of Crigler-Najjar syndrome type I (CN-I) [MIM:218800]. CN-I patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN-I inheritance is autosomal recessive [P22309 ];

Defects in UGT1A1 are the cause of Gilbert syndrome [MIM:143500]. Gilbert syndrome occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague nonspecific complaints [P22309 ];

Defects in UGT1A1 are the cause of Crigler-Najjar syndrome type II (CN-II) [MIM:606785]. CN-II patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN-II inheritance is autosomal dominant [P22309 ];

Links

SwissProt

O60656; O75310; O75795; P06133; P16662; P19224; P22309; P22310; P35503; P35504; P36537; P54855; Q3SY77; Q4R0Z5; Q4R0Z6; Q4R0Z7; Q5K632; Q5K672; Q5K673; Q5K674; Q5QTD9; Q5QTE0; Q5QTE1; Q5QTE2; Q5QTE3; Q5QTE4; Q5QTE5; Q6NUS8; Q6UWM9; Q9BY64; Q9HAW7; Q9HAW8; Q9HAW9; Q9Y4X1

Entrez Gene

10720; 10941; 54490; 54575; 54576; 54577; 54578; 54579; 54600; 54657; 54658; 54659; 7363; 7364; 7365; 7366; 7367; 79799

HPRD

07073; 07335; 08933; 05279; 08402; 07072; 07071; 02508; 07193; 07566; 03545; 04345; 05931; 08646; 02507; 07336; 07192; 09397



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min