Information on EC 2.4.1.95 - bilirubin-glucuronoside glucuronosyltransferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.4.1.95
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RECOMMENDED NAME
GeneOntology No.
bilirubin-glucuronoside glucuronosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 bilirubin-glucuronoside = bilirubin + bilirubin-bisglucuronoside
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glucuronyl group transfer
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hexosyl group transfer
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SYSTEMATIC NAME
IUBMB Comments
bilirubin-glucuronoside:bilirubin-glucuronoside D-glucuronosyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
71822-22-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 bilirubin-glucuronoside
bilirubin + bilirubin 8,12-diglucuronide
show the reaction diagram
acetaminophen + UDP-glucuronate
?
show the reaction diagram
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-
-
?
bilirubin monoglucuronide + bilirubin monoglucuronide
bilirubin diglucuronide + bilirubin
show the reaction diagram
serotonin + UDP-glucuronate
UDP + 3-(2-aminoethyl)-1H-indol-5-yl beta-D-glucuronide
show the reaction diagram
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-
-
?
UDP-glucuronate + 1-naphthol
UDP + beta-D-glucuronosyl-(1-naphthol)
show the reaction diagram
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-
-
?
UDP-glucuronate + 4-methylumbelliferone
UDP + beta-D-glucuronosyl-(4-methylumbelliferone)
show the reaction diagram
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-
-
?
UDP-glucuronate + 4-nitrophenol
UDP + 4-nitrophenol beta-D-glucuronide
show the reaction diagram
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-
-
?
UDP-glucuronate + buprenorphine
UDP + buprenorphine glucuronide
show the reaction diagram
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-
-
?
UDP-glucuronic acid + bilirubin
bilirubin glucuronoside + UDP
show the reaction diagram
UDP-glucuronic acid + bilirubin
UDP + bilirubin O-glucuronide
show the reaction diagram
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-
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?
UDP-glucuronic acid + diclofenac
UDP + diclofenac O-glucuronide
show the reaction diagram
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-
-
-
?
UDP-glucuronic acid + estradiol
UDP + estradiol 3-O-glucuronide
show the reaction diagram
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-
-
-
?
UDP-glucuronic acid + imipramine
UDP + imipramine N-glucuronide
show the reaction diagram
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-
-
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?
UDP-glucuronic acid + serotonin
UDP + serotonin O-glucuronide
show the reaction diagram
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-
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?
UDP-glucuronic acid + trifluoperazine
UDP + trifluoperazine N-glucuronide
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 bilirubin-glucuronoside
bilirubin + bilirubin 8,12-diglucuronide
show the reaction diagram
additional information
?
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bilirubin is metabolized solely by UGT1A1
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-naphthol
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4-hydroxyphenytoin
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4-Methylumbelliferone
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7-ethyl-10-hydroxycamptothecin
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weak inhibitor of bilirubin glucuronidation
alpha-linolenic acid
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anthraflavic acid
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arachidonic acid
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atazanavir
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baicalein
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carvedilol
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daidzein
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docosahexaenoic acid
eicosapentaenoic acid
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erlotinib
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ethinylestradiol
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farnesol
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indinavir
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ketoconazole
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levothyroxine
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linoleic acid
niflumic acid
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oleic acid
palmitoleic acid
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raltegravir
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riluzole
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ritonavir
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sorafenib
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-
additional information
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all of the fatty acids that strongly inhibit UGT1A1 activity are unsaturated fatty acids, and fatty acids that do not inhibit UGT1A1 are all saturated fatty acids, i.e. stearic acid, myristic acid, lauric acid, palmitic acid, behenic acid, arachidic acid, lignoceric acid, and decanoic acid
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
6-formylindolo[3,2-b]carbazole
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treatment of the HaCaT cells with 6-formylindolo[3,2-b]carbazole, which is one of the tryptophan derivatives formed by UVB, results in an induction of UGT1A1 mRNA and activity. Positive effects of UVB irradiation on the expression of UGT1A1 in the skin and HaCaT cells
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
bilirubin
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.033 - 0.035
bilirubin monoglucuronide
0.00045 - 0.00066
bilirubin-glucuronoside
additional information
additional information
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0018 - 0.0052
docosahexaenoic acid
0.0221 - 0.024
linoleic acid
0.0234 - 0.0293
oleic acid
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.24
1-naphthol
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.12
4-hydroxyphenytoin
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.1
4-Methylumbelliferone
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.3564
7-ethyl-10-hydroxycamptothecin
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0261
alpha-linolenic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.0036
anthraflavic acid
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0227
arachidonic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.007
baicalein
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.027
carvedilol
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0073
daidzein
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0116
docosahexaenoic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.0199
eicosapentaenoic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.021
ethinylestradiol
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.047
farnesol
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.027
ketoconazole
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0049
levothyroxine
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0331
linoleic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.053
niflumic acid
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.0316
oleic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.0371
palmitoleic acid
Homo sapiens
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pH 7.4, 37C, inhibition of recombinant enzyme
0.17
raltegravir
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.18
riluzole
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.003
ritonavir
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
0.36
SN-38
Homo sapiens
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in 100 mM Tris-HCl buffer (pH 7.4) with 5 mM MgCl2, at 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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recombinant enzyme
Manually annotated by BRENDA team
additional information
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in neonates, the expression of UGT1A1 is greater in the skin, while in adults, UGT1A1 is expressed mainly in the liver
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28000
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x * 28000, SDS-PAGE
50000
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SDS-PAGE, each UGT1A isoform shows a single band at 50 to 55 kDa, owing to the differences in the levels of glycosylation
160000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
following incubation of solubilized plasma membrane with pronase at 37C for 180 min, 80% of enzyme activity is lost
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in HEK293 cells
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expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells; expressed in HEK293 cells
mRNA expression pattern of human UGT1A1 in human skin, human skin keratinocyte cells, and skin of humanized UGT1 mice, overview
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semi-quantitative and quantitative reverse transcription PCR enzyme expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
activation of peroxisome proliferator-activated receptors increases UGT1A1 expression, resulting in reduction of serum bilirubin levels in human infants. High concentration of fatty acids induce UGT1A1 in the liver and small intestine, especially oleic acid and linoleic acid dramatically decreased serum bilirubin levels
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D-glucose induces the enzyme expression. Formula feeding leads to dramatic induction of intestinal UGT1A1 gene expression. In transgenic hUGT1 mice, supplemental oral glucose treatments specifically induces UGT1A1 in the small intestine but not in the liver. Glucose-mediated UGT1A1 induction is also observed in human intestinal Caco-2 cells
D-glucose induces the enzyme expression. Formula feeding leads to dramatic induction of intestinal UGT1A1 gene expression. In transgenic hUGT1 mice, supplemental oral glucose treatments specifically induces UGT1A1 in the small intestine but not in the liver. Glucose-mediated UGT1A1 induction is also observed in human intestinal Caco-2 cells. Induction of UGT1A1 in the skin can contribute to bilirubin metabolism in sunlight-exposed neonates
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human breast milk directly suppresses expression of the UGT1A1 gene. In neonates, breast milk can inhibit the IKK/NF-kappaB signaling pathway, leading to repression of intestinal UGT1A1 activity. Interleukin-1beta can inhibit the constitutive androstane receptor-induced expression of the hepatic UGT1A1 gene
in neonatal transgenic hUGT1 mice, glucose induces UGT1A1 in the small intestine and in intestinal Caco-2 cells, while it does not affect the expression of UGT1A1 in the liver
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treatment of the HaCaT cells with 6-formylindolo[3,2-b]carbazole, which is one of the tryptophan derivatives formed by UVB, results in an induction of UGT1A1 mRNA and activity. Positive effects of UVB irradiation on the expression of UGT1A1 in the HaCaT cells. 4fold induction of UGT1A1 by UVB-irradiated L-tryptophan within 5 minutes. The UVB treatment of the mice induces UGT1A1 only in the skin
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F83L
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the mutant exhibits less than 5% of wild type conjugation capacity
G211A
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subtype *6, subtype *6/*6 is related to hyperbilirubinemia, diplotypes of compound haplotypes (*60/*6 and wild-type/*60 + wild-type/*28 + wild-type/*6) are significantly related to hyperbilirubinemia development
G71R
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the mutant exhibits about 30% of wild type conjugation capacity
I294T
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the mutant exhibits about 40% of wild type conjugation capacity
N400D
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the mutant exhibits about 60% of wild type conjugation capacity
R336L
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the mutant exhibits about 80% of wild type conjugation capacity
T3279G
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subtype *60, diplotypes of this subtype plus subtype *28 (*60/*60 + *28/*28) are only found in hyperbilirubinemic patients, they show highest bilirubin concentrations, this variant is not found in controls, diplotypes of compound haplotypes (*60/*28, *60/6, wild-type/*60 + wild-type/*28 + wild-type/*6) are significantly related to hyperbilirubinemia development, also *60/*60 and *60/*60 + wild-type/*28 are related to hyperbilirubinemia
W461R
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the mutant exhibits less than 5% of wild type conjugation capacity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine