BioPAX pathway converted from "Glucuronidation" in the Reactome database. Glucuronidation Glucuronidation conjugation utilizes UDP-glucuronosyltransferases (UGTs; EC 2.4.1.17) to catalyze a wide range of diverse endogenous and xenobiotic compounds. Glucuronidation is the major pathway in phase II metabolism and accounts for approximately 35% of drug conjugation. UGTs are microsomal membrane-bound and catalyze the transfer of a glucuronate group of uridine diphosphoglucuronate (UDPGA, a co-substrate) to the functional group of specific substrates. UDPGA is synthesized from glucose-1-phosphate (G1P). G1P is required for glycolysis and is present in high concentrations in the cell, making it is unlikely to be a limiting factor in UDPGA synthesis. UDP is added to G1P to form UDP-glucose which is then dehydrogenated to form UDPGA. The basic reaction is<p><b>UDP-Glucuronate + acceptor -> UDP + acceptor-beta-D-glucuronide</b></p>The effect of this conjugation is to confer polarity to the substrate which can then be easily excreted in urine or bile. Functional groups acted on include hydroxyl, carboxylate, amino and sulfate groups. There are 2 families of UGTs, UGT1 and UGT2 which are further sub-divided into 3 subfamilies, UGT1A, UGT2A and UGT2B. There are more than 26 different isozymes in humans, of which 18 are functional proteins. They are composed of 527-530 residues and have a molecular weight of 50-57KDa.<br>The UGT1 family comprises of 9 proteins (UGT1A1, 1A3-1A10) but only 5 have been isolated in humans. Example substrates which are glucuronidated are acetaminophen by UGT1A6 and bilirubin by UGT1A1. Members of the UGT2 subfamily are each encoded by their own genes, in contrast to UGT1As which are encoded at the UGT1 locus. Example substrates are morphine conjugation by UGT2B7 and androgenic steroid conjugation by UGT2B17.<br>Xenobiotics conjugated with glucuronic acid can be substrates for beta-glucuronidase, an enzyme common in gut microflora. This enzyme can release the parent or phase I metabolite which can be reabsorbed. It can then either re-exert it's original effects or be conjugated by glucuronic acid again. This cycle is called <i>enterohepatic circulation</i> and can delay the elimination of the xenobiotic. Authored: Jassal, B, 2004-11-29 11:42:34 Edited: Jassal, Bijay, 2008-05-19 Formation of the active cofactor, UDP-glucuronate Glucose 1-phosphate and UTP are the precursors to UDP-glucuronate formation. After oxidation of the resultant complex, UDP-glucuronate is transported to the ER lumen. Authored: Jassal, B, 2004-11-30 16:21:24 Edited: Jassal, Bijay, 2008-05-19 LEFT-TO-RIGHT 2.7.7.9 UTP + D-glucose 1-phosphate <=> pyrophosphate + UDP-glucose Cytosolic UDP-glucose pyrophosphorylase 2 (UGP2) catalyzes the reaction of UTP and glucose 1-phosphate to form UDP glucose and pyrophosphate (Knop and Hansen 1970; Duggleby et al. 1996). UGP2 is inferred to occur in the cell as a homooctamer from studies of its bovine homologue (Levine et al. 1969). Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 UTP uridine 5'-triphosphate Uridine triphosphate Reactome DB_ID: 29494 cytosol GENE ONTOLOGY GO:0005829 UTP(4-) [ChEBI:46398] UTP(4-) UTP utp uridine 5'-triphosphate(4-) URIDINE 5'-TRIPHOSPHATE ChEBI CHEBI:46398 Reactome Database ID Release 81 29494 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29494 Reactome R-ALL-29494 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29494.3 Reactome http://www.reactome.org COMPOUND C00075 additional information MI MI:0361 G1P D-glucopyranose 1-phosphate(2-) D-Glucose 1-phosphate D-glucopyranose 1-phosphate alpha-D-Glucose 1-phosphate Cori ester D-Glucose alpha-1-phosphate Reactome DB_ID: 29548 D-glucopyranose 1-phosphate(2-) [ChEBI:57629] D-glucopyranose 1-phosphate(2-) 1-O-phosphonato-D-glucopyranose D-glucopyranose 1-phosphate anion D-glucopyranose 1-phosphate D-glucopyranose 1-phosphate dianion ChEBI CHEBI:57629 Reactome Database ID Release 81 29548 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29548 Reactome R-ALL-29548 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29548.4 UDP-Glc UDP-D-glucose(2-) UDP-glucose UDP-D-glucose UDPglucose Reactome DB_ID: 29410 UDP-D-glucose(2-) [ChEBI:58367] UDP-D-glucose(2-) UDP-D-glucose dianion UDP-Glc(2-) ChEBI CHEBI:58367 Reactome Database ID Release 81 29410 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29410 Reactome R-ALL-29410 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29410.4 COMPOUND C00029 PPi pyrophosphate diphosphoric acid pyrophosphoric acid diphosphate Reactome DB_ID: 111294 diphosphate(3-) [ChEBI:33019] diphosphate(3-) ChEBI CHEBI:33019 Reactome Database ID Release 81 111294 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111294 Reactome R-ALL-111294 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-111294.4 COMPOUND C00013 ACTIVATION 8xUGP2 UGP2 octamer UDP-glucose pyrophosphorylase 2 octamer Reactome DB_ID: 70281 UGP2 UDP-glucose pyrophosphorylase 2 UTP-glucose-1-phosphate uridylyltransferase Reactome DB_ID: 453128 UniProt:Q16851 UGP2 UGP2 UGP1 FUNCTION UTP--glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.PATHWAY Glycan biosynthesis; glycogen biosynthesis.SUBUNIT Homooctamer.TISSUE SPECIFICITY Highly expressed in various brain regions. Expressed in amygdala, anterior cingulate cortex, caudate, cerebellar hemisphere, cerebellum, cortex, frontal cortex, hippocampus, hypothalamus, nucleus accumbens, putamen, spinal cord and substantia nigra (PubMed:31820119). Also widely expressed among other tissues, including liver, heart, placenta, lung, kidney, pancreas and skeletal muscle (PubMed:8354390, PubMed:8631325).SIMILARITY Belongs to the UDPGP type 1 family.CAUTION The human genome was initially thought to contain 2 genes for UTP--glucose-1-phosphate uridylyltransferase: UGP1 and UGP2 (PubMed:8354390, PubMed:8631325). However, the sequence defined as UGP1 (PubMed:8354390) probably does not exist and corresponds to UGP2. Homo sapiens NCBI Taxonomy 9606 UniProt Q16851 1 EQUAL 508 EQUAL Reactome Database ID Release 81 453128 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=453128 Reactome R-HSA-453128 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-453128.1 8 Reactome Database ID Release 81 70281 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70281 Reactome R-HSA-70281 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70281.1 GENE ONTOLOGY GO:0003983 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 81 70285 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70285 Reactome Database ID Release 81 70286 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70286 Reactome R-HSA-70286 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70286.4 8631325 Pubmed 1996 Sequence differences between human muscle and liver cDNAs for UDPglucose pyrophosphorylase and kinetic properties of the recombinant enzymes expressed in Escherichia coli. Duggleby, RG Chao, YC Huang, JG Peng, HL Chang, HY Eur J Biochem 235:173-9 5427280 Pubmed 1970 Uridine diphosphate glucose pyrophosphorylase. IV. Crystallization and properties of the enzyme from human liver Knop, JK Hansen, RG J Biol Chem 245:2499-504 5348606 Pubmed 1969 Uridine diphosphate glucose pyrophosphorylase. II Levine, S Gillett, TA Hageman, E Hansen, RG J Biol Chem 244:5729-34 LEFT-TO-RIGHT 1.1.1.22 UDP-glucose is oxidised to UDP-glucuronate UDP-glucose dehydrogenase (UGDH) catalyzes the conversion of UDP-glucose to UDP-glucuronic acid. The cytosolic enzyme is active as a hexamer and performs two successive oxidations to convert the 6'-hydroxyl of UDP-glucose to a carboxylate with concurrent reduction of 2 mol of NAD+ to NADH. Authored: Jassal, Bijay, 2006-02-14 Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 Edited: Jassal, Bijay, 2006-02-14 NAD NAD+ NAD(+) Nicotinamide adenine dinucleotide DPN Diphosphopyridine nucleotide Reactome DB_ID: 29360 NAD(1-) [ChEBI:57540] NAD(1-) adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NAD(+) NAD anion ChEBI CHEBI:57540 Reactome Database ID Release 81 29360 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29360 Reactome R-ALL-29360 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29360.5 COMPOUND C00003 2 H2O water Reactome DB_ID: 29356 water [ChEBI:15377] water ChEBI CHEBI:15377 Reactome Database ID Release 81 29356 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356 Reactome R-ALL-29356 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5 COMPOUND C00001 UDP-GlcA UDP-glucuronate UDP-alpha-D-glucuronate Reactome DB_ID: 158601 UDP-alpha-D-glucuronate(3-) [ChEBI:58052] UDP-alpha-D-glucuronate(3-) UDP-alpha-D-glucuronate trianion UDP-alpha-D-glucuronate ChEBI CHEBI:58052 Reactome Database ID Release 81 158601 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158601 Reactome R-ALL-158601 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158601.4 COMPOUND C00167 H+ proton hydron Reactome DB_ID: 70106 hydron [ChEBI:15378] hydron ChEBI CHEBI:15378 Reactome Database ID Release 81 70106 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70106 Reactome R-ALL-70106 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4 COMPOUND C00080 2 NADH Reactome DB_ID: 73473 NADH(2-) [ChEBI:57945] NADH(2-) NADH dianion adenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate} NADH ChEBI CHEBI:57945 Reactome Database ID Release 81 73473 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=73473 Reactome R-ALL-73473 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-73473.4 COMPOUND C00004 2 ACTIVATION 6xUGDH UDP-glucose dehydrogenase hexamer Reactome DB_ID: 173600 UGDH UDP-glucose dehydrogenase Reactome DB_ID: 173598 UniProt:O60701 UGDH UGDH FUNCTION Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21961565, PubMed:21502315, PubMed:23106432, PubMed:22123821, PubMed:25478983, PubMed:27966912, PubMed:30420606, PubMed:30457329). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity). Required for proper brain and neuronal development (PubMed:32001716).ACTIVITY REGULATION UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor. It binds at the same site as the substrate, but functions as allosteric inhibitor by triggering a conformation change that disrupts the active hexameric ring structure and gives rise to an inactive, horseshoe-shaped hexamer.PATHWAY Nucleotide-sugar biosynthesis; UDP-alpha-D-glucuronate biosynthesis; UDP-alpha-D-glucuronate from UDP-alpha-D-glucose: step 1/1.SUBUNIT Homohexamer.TISSUE SPECIFICITY Detected in heart, placenta, liver, pancreas, spleen, thymus, prostate, ovary, small intestine and colon (PubMed:9737970). Widely expressed (PubMed:9737970).DOMAIN The protein goes through several conformation states during the reaction cycle, giving rise to hysteresis. In the initial state, the ligand-free protein is in an inactive conformation (E*). Substrate binding triggers a change to the active conformation (E). UDP-xylose binding triggers the transition to a distinct, inhibited conformation. The presence of an intrinsically disordered C-terminus promotes a more dynamic protein structure and favors a conformation with high affinity for UPD-xylose.DOMAIN The allosteric switch region moves by about 5 Angstroms when UDP-xylose is bound, and occupies part of the UDP-glucose binding site. At the same time it promotes domain movements that disrupt the active hexameric ring structure and lead to the formation of a horseshoe-shaped, inactive hexamer.SIMILARITY Belongs to the UDP-glucose/GDP-mannose dehydrogenase family. UniProt O60701 1 EQUAL 494 EQUAL Reactome Database ID Release 81 173598 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173598 Reactome R-HSA-173598 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173598.1 6 Reactome Database ID Release 81 173600 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173600 Reactome R-HSA-173600 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173600.1 GENE ONTOLOGY GO:0003979 Reactome Database ID Release 81 173601 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173601 Reactome Database ID Release 81 173597 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173597 Reactome R-HSA-173597 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173597.1 15044486 Pubmed 2004 Characterization of human UDP-glucose dehydrogenase. CYS-276 is required for the second of two successive oxidations Sommer, BJ Barycki, JJ Simpson, MA J Biol Chem 279:23590-6 LEFT-TO-RIGHT SLC35D1 hexamer transports UDP-GlcA, UDP-GlcNAc from cytosol to endoplasmic reticulum lumen The UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter (SLC35D1) in hexameric form transports both UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) from the cytosol into the ER lumen across the ER membrane (Muraoka et al. 2001). These substrates participate in glucuronidation and/or chondroitin sulfate biosynthesis. Authored: Jassal, Bijay, 2006-02-17 Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 Edited: Jassal, Bijay, 2006-02-17 UDP-GlcNAc UDP-N-acetyl-alpha-D-glucosamine(2-) UDP-N-acetyl-D-glucosamine UDP-N-acetyl-alpha-D-glucosamine UDP-N-acetylglucosamine Reactome DB_ID: 162756 UDP-N-acetyl-alpha-D-glucosamine(2-) [ChEBI:57705] UDP-N-acetyl-alpha-D-glucosamine(2-) UDP-N-acetyl-alpha-D-glucosamine UDP-N-acetyl-alpha-D-glucosamine dianion uridine 5'-[3-(acetamido-2-deoxy-alpha-D-glucopyranosyl) diphosphate] ChEBI CHEBI:57705 Reactome Database ID Release 81 162756 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=162756 Reactome R-ALL-162756 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-162756.4 UDP-GlcNAc UDP-N-acetyl-alpha-D-glucosamine(2-) UDP-N-acetyl-D-glucosamine UDP-N-acetyl-alpha-D-glucosamine UDP-N-acetylglucosamine Reactome DB_ID: 3499326 endoplasmic reticulum lumen GENE ONTOLOGY GO:0005788 Reactome Database ID Release 81 3499326 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3499326 Reactome R-ALL-3499326 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3499326.4 UDP-GlcA UDP-glucuronic acid UDP-alpha-D-glucuronic acid Reactome DB_ID: 174384 Reactome Database ID Release 81 174384 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174384 Reactome R-ALL-174384 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174384.4 COMPOUND C00167 ACTIVATION SLC35D1 hexamer UDP-glucuronate transporter homohexamer Reactome DB_ID: 174388 endoplasmic reticulum membrane GENE ONTOLOGY GO:0005789 SLC35D1 UDP-glucuronate transporter Reactome DB_ID: 174361 UniProt:Q9NTN3 SLC35D1 SLC35D1 KIAA0260 UGTREL7 FUNCTION Transports both UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) from the cytoplasm into the endoplasmic reticulum lumen (PubMed:11322953, PubMed:17952091). Plays a role in chondroitin sulfate biosynthesis, which is important for formation of cartilage extracellular matrix and normal skeletal development (By similarity).TISSUE SPECIFICITY Ubiquitous.SIMILARITY Belongs to the TPT transporter family. SLC35D subfamily. UniProt Q9NTN3 1 EQUAL 355 EQUAL Reactome Database ID Release 81 174361 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174361 Reactome R-HSA-174361 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174361.1 6 Reactome Database ID Release 81 174388 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174388 Reactome R-HSA-174388 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174388.1 GENE ONTOLOGY GO:0005461 Reactome Database ID Release 81 174365 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174365 Reactome Database ID Release 81 174368 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174368 Reactome R-HSA-174368 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174368.1 11322953 Pubmed 2001 Molecular characterization of human UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter, a novel nucleotide sugar transporter with dual substrate specificity Muraoka, M Kawakita, M Ishida, N FEBS Lett 495:87-93 Reactome Database ID Release 81 173599 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173599 Reactome R-HSA-173599 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173599.1 17482904 Pubmed 2007 Molecular mechanism of phase I and phase II drug-metabolizing enzymes: implications for detoxification Iyanagi, T Int Rev Cytol 260:35-112 GENE ONTOLOGY GO:0006065 gene ontology term for cellular process MI MI:0359 LEFT-TO-RIGHT 2.4.1.17 UGTs transfer GlcA from UDP-GlcA to O-centre substrates Typical O-centred substrates were chosen as examples for these isozymes. Many UDP-glucuronosyltransferases (UGTs) can transfer the glucuronyl moiety (GlcA) from UDP-GlcA to the O-centre functional group of many substrates, including salicylate (ST), to form 4-O-glucuronides (Casarett & Doull 1995, Babu et al. 1996; Kuehl et al, 2006). Authored: Jassal, B, 2006-02-23 09:32:09 Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 Reviewed: D'Eustachio, Peter, 2017-01-06 Edited: Jassal, B, 2006-02-23 09:32:09 Converted from EntitySet in Reactome O-centre functional group substrate Reactome DB_ID: 174911 paracetamol Acetaminophen (TN TYLENOL) Reactome DB_ID: 39427 paracetamol [ChEBI:46195] paracetamol ChEBI CHEBI:46195 Reactome Database ID Release 81 39427 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=39427 Reactome R-ALL-39427 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-39427.3 COMPOUND C06804 DSQ Debrisoquine debrisoquin Reactome DB_ID: 211993 debrisoquin [ChEBI:34665] debrisoquin Isocaramidine Debrisochinum ChEBI CHEBI:34665 Reactome Database ID Release 81 211993 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=211993 Reactome R-ALL-211993 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-211993.3 NHABP N-hydroxy-4-aminobiphenyl Reactome DB_ID: 34889 N-hydroxy-4-aminobiphenyl [ChEBI:16580] N-hydroxy-4-aminobiphenyl ChEBI CHEBI:16580 Reactome Database ID Release 81 34889 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=34889 Reactome R-ALL-34889 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-34889.3 COMPOUND C03622 PhOH Benzenol phenol Hydroxybenzene Phenic acid Phenylic acid Reactome DB_ID: 29630 phenol [ChEBI:15882] phenol ChEBI CHEBI:15882 Reactome Database ID Release 81 29630 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29630 Reactome R-ALL-29630 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29630.3 COMPOUND C00146 ST (hepatocyte) salicylate (hepatocyte) Reactome DB_ID: 9749790 salicylate [ChEBI:30762] salicylate sal o-hydroxybenzoate 2-hydroxybenzoic acid ion(1-) ChEBI CHEBI:30762 Reactome Database ID Release 81 9749790 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9749790 Reactome R-ALL-9749790 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-9749790.1 Reactome Database ID Release 81 174911 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174911 Reactome R-ALL-174911 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174911.2 UDP uridine 5'-diphosphate Reactome DB_ID: 158602 UDP [ChEBI:17659] UDP ChEBI CHEBI:17659 Reactome Database ID Release 81 158602 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158602 Reactome R-ALL-158602 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158602.2 COMPOUND C00015 Converted from EntitySet in Reactome O-glucuronide Reactome DB_ID: 174914 APAP-GlcA Acetaminophen O-glucuronate acetaminophen O-beta-D-glucosiduronate Reactome DB_ID: 158604 acetaminophen O-beta-D-glucosiduronate [ChEBI:132962] acetaminophen O-beta-D-glucosiduronate p-acetamidophenyl beta-D-glucopyranosiduronate p-acetamidophenyl beta-D-glucuronide(1-) 4-acetamidophenyl beta-D-glucosiduronate p-acetamidophenyl beta-D-glucosiduronate 4-acetamidophenyl beta-D-glucopyranosiduronate 4-acetamidophenyl beta-D-glucuronide(1-) ChEBI CHEBI:132962 Reactome Database ID Release 81 158604 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158604 Reactome R-ALL-158604 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158604.5 DSQ-OG Debrisoquine O-glucuronide N-hydroxydebrisoquine O-glucuronide Reactome DB_ID: 351779 N-hydroxydebrisoquine O-glucuronide [ChEBI:65137] N-hydroxydebrisoquine O-glucuronide ChEBI CHEBI:65137 Reactome Database ID Release 81 351779 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351779 Reactome R-ALL-351779 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-351779.3 N-hydroxy-4-aminobiphenyl O-glucuronide Reactome DB_ID: 158727 N-hydroxy-4-aminobiphenyl O-glucuronide [ChEBI:32649] N-hydroxy-4-aminobiphenyl O-glucuronide Source N-hydroxy-4-aminobiphenyl glucuronide ChEBI CHEBI:32649 Reactome Database ID Release 81 158727 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158727 Reactome R-ALL-158727 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158727.2 Phenyl glucuronate phenol O-(beta-D-glucuronide) Reactome DB_ID: 158857 phenol O-(beta-D-glucuronide) [ChEBI:64681] phenol O-(beta-D-glucuronide) ChEBI CHEBI:64681 Reactome Database ID Release 81 158857 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158857 Reactome R-ALL-158857 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158857.3 SAPG salicylic acid phenolic gluconate 1-salicylate O-glucuronide(1-) Reactome DB_ID: 9750002 1-salicylate O-glucuronide(1-) [ChEBI:176976] 1-salicylate O-glucuronide(1-) ChEBI CHEBI:176976 Reactome Database ID Release 81 9750002 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9750002 Reactome R-ALL-9750002 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-9750002.1 Reactome Database ID Release 81 174914 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174914 Reactome R-ALL-174914 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174914.2 ACTIVATION Converted from EntitySet in Reactome UGTs (O-GlcA forming) UDP-glucuronosyltransferase (O-glucuronide forming isozymes) Reactome DB_ID: 174920 UGT1A1 Reactome DB_ID: 159156 UniProt:P22309 UGT1A1 UGT1A1 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2 (PubMed:17187418, PubMed:20610558). Isoform 1 also interacts with respective i2 isoforms of UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).POLYMORPHISM Genetic variation in UGT1A1 defines the bilirubin serum levels quantitative trait locus 1 (BILIQTL1) [MIM:601816]. Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism.MISCELLANEOUS UGT1A1 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P22309 26 EQUAL 533 EQUAL Reactome Database ID Release 81 159156 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159156 Reactome R-HSA-159156 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159156.1 UGT1A6 Reactome DB_ID: 158597 UniProt:P19224 UGT1A6 UGT1A6 GNT1 UGT1 FUNCTION UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).SUBUNIT Isoform 1 interacts with isoform 3/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 3. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A7, UGT1A8, UGT1A9 and UGT1A10.TISSUE SPECIFICITY Expressed in skin. Isoforms 1 and 3 are expressed in kidney and liver. Isoform 1 but not isoform 2 is expressed in colon, esophagus and small intestine.POLYMORPHISM Polymorphisms in the UGT1A6 gene define four common haplotypes: UGT1A6*1, UGT1A6*2, UGT1A6*3 and UGT1A6*4. Liver tissue samples that were homozygous for UGT1A6*2 exhibited a high rate of glucuronidation relative to tissues with other genotypes. Biochemical kinetic studies indicate that the UGT1A6*2 allozyme, expressed homozygously, had almost two-fold greater activity toward p-nitrophenol than UGT1A6*1 and when expressed heterozygously (UGT1A6*1/*2) it is associated with low enzyme activity. Common genetic variation in UGT1A6 confers functionally significant differences in biochemical phenotype. This genetic variation might impact clinical efficacy or toxicity of drugs metabolized by UGT1A6.MISCELLANEOUS The gene is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P19224 27 EQUAL 532 EQUAL Reactome Database ID Release 81 158597 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158597 Reactome R-HSA-158597 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-158597.1 UGT1A3 Reactome DB_ID: 174928 UniProt:P35503 UGT1A3 UGT1A3 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).MISCELLANEOUS UGT1A3 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P35503 29 EQUAL 534 EQUAL Reactome Database ID Release 81 174928 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174928 Reactome R-HSA-174928 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174928.1 UGT1A4 Reactome DB_ID: 159157 UniProt:P22310 UGT1A4 UGT1A4 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).INDUCTION Induced by phenobarbital.MISCELLANEOUS UGT1A4 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P22310 29 EQUAL 534 EQUAL Reactome Database ID Release 81 159157 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159157 Reactome R-HSA-159157 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159157.1 UGT1A5 Reactome DB_ID: 174913 UniProt:P35504 UGT1A5 UGT1A5 GNT1 UGT1 SUBUNIT Homodimer (By similarity). Homooligomer (By similarity). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (By similarity). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (By similarity).TISSUE SPECIFICITY Isoform 1 and isoform 2 are expressed in colon and small intestine. Neither isoform is expressed in liver, kidney or esophagus.MISCELLANEOUS UGT1A5 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P35504 29 EQUAL 534 EQUAL Reactome Database ID Release 81 174913 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174913 Reactome R-HSA-174913 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174913.1 UGT1A7 Reactome DB_ID: 174927 UniProt:Q9HAW7 UGT1A7 UGT1A7 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).TISSUE SPECIFICITY Liver and gastric tissue (PubMed:9271343). Isoform 1 and isoform 2 are expressed in esophagus. Neither isoform is expressed in liver, kidney, colon and small intestine (PubMed:18004212).POLYMORPHISM There are four common allelic UGT1A7 variants which exhibit significant differences in catalytic activity towards 3-, 7-, and 9-hydroxy-benzo(a)pyrene. UGT1A7*3 exhibits a 5.8-fold lower relative Vmax compared to UGT1A7*1, whereas UGT1A7*2 and UGT1A7*4 have a 2.6- and 2.8-fold lower relative Vmax than UGT1A7*1, respectively, suggesting that these mutations confer slow glucuronidation phenotype.MISCELLANEOUS UGT1A7 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q9HAW7 26 EQUAL 530 EQUAL Reactome Database ID Release 81 174927 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174927 Reactome R-HSA-174927 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174927.1 UGT1A8 Reactome DB_ID: 174925 UniProt:Q9HAW9 UGT1A8 UGT1A8 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A9 and UGT1A10 (PubMed:20610558).MISCELLANEOUS UGT1A8 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q9HAW9 26 EQUAL 530 EQUAL Reactome Database ID Release 81 174925 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174925 Reactome R-HSA-174925 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174925.1 UGT1A9 UDP-glucuronosyltransferase 1-9 UD19_HUMAN Reactome DB_ID: 400210 UniProt:O60656 UGT1A9 UGT1A9 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10 (PubMed:20610558).MISCELLANEOUS UGT1A9 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt O60656 26 EQUAL 530 EQUAL Reactome Database ID Release 81 400210 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=400210 Reactome R-HSA-400210 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-400210.1 UGT2A1 UDP-glucuronosyltransferase 2A1 UD2A1_HUMAN Reactome DB_ID: 9698803 UniProt:P0DTE4 UGT2A1 UGT2A1 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10359671, PubMed:19858781, PubMed:18719240, PubMed:19022937, PubMed:23756265, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:10359671, PubMed:19858781, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone and epitestosterone) and estrogens (estradiol and epiestriol) (PubMed:18719240, PubMed:19858781, PubMed:19022937, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Shows a high affinity to aliphatic odorants such as citronellol as well as olfactory tissue specificity, and therefore may be involved in olfaction (PubMed:10359671). Shows a potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth (PubMed:19858781).TISSUE SPECIFICITY Olfactory epithelium, brain and fetal lung (PubMed:10359671). Not present in liver (PubMed:10359671).MISCELLANEOUS UGT2A1 isoform is part of the UGT2A complex locus which displays alternative use of promoters and exons. The locus is defined by 2 alternative promoters giving rise to 2 fonctionally active polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results in additional isoforms for each protein class.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P0DTE4 21 EQUAL 527 EQUAL Reactome Database ID Release 81 9698803 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9698803 Reactome R-HSA-9698803 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9698803.1 UGT2A2 UDP-glucuronosyltransferase 2A2 UD2A2_HUMAN Reactome DB_ID: 9698802 UniProt:P0DTE5 UGT2A2 UGT2A2 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:19858781, PubMed:18719240, PubMed:23756265, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:19858781, PubMed:23756265). Catalyzes the glucuronidation of endogenous estrogen hormone estradiol (PubMed:18719240, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Shows a potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth (PubMed:19858781).TISSUE SPECIFICITY Mainly expressed in the nasal mucosa.MISCELLANEOUS UGT2A2 isoform is part of the UGT2A complex locus which displays alternative use of promoters and exons. The locus is defined by 2 alternative promoters resulting in 2 fonctionally active polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results in additional isoforms for each protein class.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P0DTE5 1 EQUAL 536 EQUAL Reactome Database ID Release 81 9698802 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9698802 Reactome R-HSA-9698802 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9698802.1 UGT2B10 Reactome DB_ID: 174919 UniProt:P36537 UGT2B10 UGT2B10 FUNCTION UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P36537 24 EQUAL 528 EQUAL Reactome Database ID Release 81 174919 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174919 Reactome R-HSA-174919 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174919.1 UGT2B11 Reactome DB_ID: 174923 UniProt:O75310 UGT2B11 UGT2B11 FUNCTION UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.TISSUE SPECIFICITY Widely expressed.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt O75310 22 EQUAL 529 EQUAL Reactome Database ID Release 81 174923 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174923 Reactome R-HSA-174923 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174923.1 UGT2B15 Reactome DB_ID: 174935 UniProt:P54855 UGT2B15 UGT2B15 UGT2B8 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:7835232, PubMed:9295060, PubMed:16595710, PubMed:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:7835232, PubMed:9295060, PubMed:16595710, PubMed:18719240, PubMed:23288867). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity).TISSUE SPECIFICITY Expressed in many tissues. Present in liver, prostate and testis.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P54855 24 EQUAL 530 EQUAL Reactome Database ID Release 81 174935 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174935 Reactome R-HSA-174935 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174935.1 UGT2B17 Reactome DB_ID: 159276 UniProt:O75795 UGT2B17 UGT2B17 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:8798464, PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol) (PubMed:8798464, PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867).TISSUE SPECIFICITY Expressed in various tissues including the liver, kidney, testis, uterus, placenta, mammary gland, adrenal gland, skin and prostate.POLYMORPHISM Copy-number variation of UGT2B17 defines the bone mineral density quantitative trait locus 12 (BMND12) [MIM:612560]. Variance in bone mineral density is a susceptibility factor for osteoporotic fractures.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt O75795 24 EQUAL 530 EQUAL Reactome Database ID Release 81 159276 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159276 Reactome R-HSA-159276 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159276.1 UGT2B28 UDP-glucuronosyltransferase 2B28 UDB28_HUMAN Reactome DB_ID: 2990863 UniProt:Q9BY64 UGT2B28 UGT2B28 TISSUE SPECIFICITY Expressed in the liver, breast and kidney.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q9BY64 25 EQUAL 529 EQUAL Reactome Database ID Release 81 2990863 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2990863 Reactome R-HSA-2990863 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2990863.1 UGT2B4 Reactome DB_ID: 158740 UniProt:P06133 UGT2B4 UGT2B4 UGT2B11 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18719240, PubMed:23288867). Catalyzes the glucuronidation of the endogenous estrogen hormones such as estradiol and estriol (PubMed:18719240, PubMed:23288867).SIMILARITY Belongs to the UDP-glycosyltransferase family.CAUTION UGT2B4 has been previously described as an enzyme named UGT2B11. However the name UGT2B11 has now been reused for another human protein (see AC O75310). UniProt P06133 24 EQUAL 528 EQUAL Reactome Database ID Release 81 158740 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158740 Reactome R-HSA-158740 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-158740.1 UGT2B7 Reactome DB_ID: 174924 UniProt:P16662 UGT2B7 UGT2B7 UGTB2B9 FUNCTION UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15472229, PubMed:15470161, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143, PubMed:17442341). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:2159463, PubMed:15472229, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:26220143, PubMed:17442341). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161).POLYMORPHISM 2 alleles have been identified: UGT2B7*1 (His-268) and UGT2B7*2 (Tyr-268). The sequence shown is that of allele UGT2B7*2.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt P16662 24 EQUAL 529 EQUAL Reactome Database ID Release 81 174924 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174924 Reactome R-HSA-174924 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174924.1 UGT2A3 UDP-glucuronosyltransferase 2A3 UD2A3_HUMAN Reactome DB_ID: 8941749 UniProt:Q6UWM9 UGT2A3 UGT2A3 UNQ2559/PRO6239 FUNCTION UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q6UWM9 24 EQUAL 527 EQUAL Reactome Database ID Release 81 8941749 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941749 Reactome R-HSA-8941749 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941749.1 UGT3A1 UDP-glucuronosyltransferase 3A1 UD3A1_HUMAN Reactome DB_ID: 8941752 UniProt:Q6NUS8 UGT3A1 UGT3A1 FUNCTION UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q6NUS8 23 EQUAL 523 EQUAL Reactome Database ID Release 81 8941752 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941752 Reactome R-HSA-8941752 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941752.1 UGT3A2 UDP-glucuronosyltransferase 3A2 UD3A2_HUMAN Reactome DB_ID: 8941751 UniProt:Q3SY77 UGT3A2 UGT3A2 PSEC0073 UNQ842/PRO1780 FUNCTION UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q3SY77 23 EQUAL 523 EQUAL Reactome Database ID Release 81 8941751 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941751 Reactome R-HSA-8941751 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941751.1 Reactome Database ID Release 81 174920 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174920 Reactome R-HSA-174920 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174920.4 GENE ONTOLOGY GO:0015020 Reactome Database ID Release 81 174915 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174915 Reactome Database ID Release 81 174931 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174931 Reactome R-HSA-174931 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174931.4 9780071470513 ISBN 1995 Casarett and Doull's Toxicology 5th Edn Parkinson, A Casarett and Doull's Toxicology 5th Edn (Book): 113-186 8687483 Pubmed 1996 Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolites. pH stability and synthesis by human and dog liver. Babu, SR Lakshmi, VM Huang, GP Zenser, TV Davis, BB Biochem Pharmacol 51:1679-85 16258079 Pubmed 2006 Glucuronidation of the aspirin metabolite salicylic acid by expressed UDP-glucuronosyltransferases and human liver microsomes Kuehl, Gwendolyn E Bigler, Jeannette Potter, John D Lampe, Johanna W Drug Metab Dispos 34:199-202 LEFT-TO-RIGHT 2.4.1.17 UGT1A1 transfers GlcA from UDP-GlcA to BIL to form BMG bilirubin + UDP-glucuronic acid => bilirubin monoglucuronide + UDP Bilirubin (BIL) is a breakdown product of heme. Its accumulation in the blood can be fatal. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. Both UGT1A1 tetramer and UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugates (Bosma et al. 1994, Ritter et al. 1992, Peters & Jansen 1986, Gorden et al. 1983, Choudhury et al. 1981, Fevery et al. 1971). Authored: Jassal, B, 2005-02-23 15:02:50 Reviewed: D'Eustachio, P, 2010-05-08 Edited: Jassal, B, 2010-05-27 BIL bilirubin bilirubin IXalpha Reactome DB_ID: 159151 bilirubin(2-) [ChEBI:57977] bilirubin(2-) bilirubin dianion 2,7,13,17-tetramethyl-1,19-dioxo-3,18-divinyl-1,10,19,22,23,24-hexahydro-21H-biline-8,12-dipropanoate bilirubin IXalpha ChEBI CHEBI:57977 Reactome Database ID Release 81 159151 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159151 Reactome R-ALL-159151 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159151.4 COMPOUND C00486 BMG Bilirubin monoglucuronide mono(glucosyluronic acid)bilirubin Reactome DB_ID: 159160 mono(glucosyluronic acid)bilirubin [ChEBI:16427] mono(glucosyluronic acid)bilirubin ChEBI CHEBI:16427 Reactome Database ID Release 81 159160 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159160 Reactome R-ALL-159160 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159160.3 COMPOUND C03374 ACTIVATION Reactome Database ID Release 81 9632040 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9632040 Reactome Database ID Release 81 9632039 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9632039 Reactome R-HSA-9632039 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9632039.1 1339448 Pubmed 1992 A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini Ritter, J K Chen, F Sheen, Y Y Tran, H M Kimura, S Yeatman, M T Owens, I S J. Biol. Chem. 267:3257-61 8027054 Pubmed 1994 Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man Bosma, PJ Seppen, J Goldhoorn, B Bakker, C Oude, Elferink RP Chowdhury, JR Chowdhury, NR Jansen, PL J Biol Chem 269:17960-4 GENE ONTOLOGY GO:0006789 LEFT-TO-RIGHT 2.4.1.17 UGT1A4 transfers GlcA from UDP-GlcA to BIL to form BMG bilirubin + UDP-glucuronic acid => bilirubin monoglucuronide + UDP Bilirubin (BIL) is a breakdown product of heme. Its accumulation in the blood can be fatal. It is highly lipophilic and thus requires conjugation to become more water soluble to aid excretion. Both UGT1A1 tetramer and UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin to form either its monoglucuronide (BMG) or diglucuronide (BDG) conjugates (Bosma et al. 1994, Ritter et al. 1992, Peters & Jansen 1986, Gorden et al. 1983, Choudhury et al. 1981, Fevery et al. 1971). Authored: Jassal, B, 2005-02-23 15:02:50 Reviewed: D'Eustachio, P, 2010-05-08 Edited: Jassal, B, 2010-05-27 ACTIVATION Reactome Database ID Release 81 9704996 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9704996 Reactome Database ID Release 81 159194 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159194 Reactome R-HSA-159194 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159194.3 6796486 Pubmed 1981 Bilirubin mono- and diglucuronide formation by human liver in vitro: assay by high-pressure liquid chromatography Chowdhury, JR Chowdhury, NR Wu, G Shouval, R Arias, IM Hepatology 1:622-7 6654901 Pubmed 1983 The hepatic microsomal formation of bilirubin diglucuronide Gordon, ER Sommerer, U Goresky, CA J Biol Chem 258:15028-36 4639028 Pubmed 1972 Bilirubin conjugates in bile of man and rat in the normal state and in liver disease Fevery, J Van, Damme B Michiels, R De Groote, J Heirwegh, KP J Clin Invest 51:2482-92 3082969 Pubmed 1986 Microsomal UDP-glucuronyltransferase-catalyzed bilirubin diglucuronide formation in human liver Peters, WH Jansen, PL J Hepatol 2:182-94 LEFT-TO-RIGHT 2.4.1.17 UGT1A1 tetramer transfers GlcA from UDP-GlcA to BMG to form BDG bilirubin monoglucuronide + UDP-glucuronic acid => bilirubin diglucuronide + UDP The principal conjugate of bilirubin in bile is bilirubin diglucuronide (BDG). The monomeric forms of UGT1A1 (Bilirubin UDP-glucuronyltransferase 1) only conjugates the first step of bilirubin conjugation to form the monoglucuronide. A tetrameric form of UGT1A1 can transfer glucuronic acid (GlcA) to bilirubin (BIL) and bilirubin monoglucuronide (BMG) to form both the monoglucuronide and the diglucuronide (BDG) conjugates respectively (Peters & Jansen 1986, Gorden et al. 1983, Choudhury et al. 1981, Fevery et al. 1971). Authored: Jassal, B, 2005-02-23 15:02:50 Reviewed: D'Eustachio, P, 2010-05-08 Edited: Jassal, B, 2010-05-27 BDG Bilirubin diglucuronide bis(beta-glucosyluronic acid)bilirubin Reactome DB_ID: 159149 bis(beta-glucosyluronate)bilirubin [ChEBI:58471] bis(beta-glucosyluronate)bilirubin 1,1'-di-O-{3,3'-[8-(carboxyethyl)-2,17-diethenyl-2,7,13,18-tetramethyl-1,19-dioxo-21,24-dihydrobila-4,15-diene-8,12-diyl]dipropanoyl}bis(beta-D-glucopyranuronate) bilirubin-bisglucuronoside ChEBI CHEBI:58471 Reactome Database ID Release 81 159149 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159149 Reactome R-ALL-159149 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159149.4 COMPOUND C05787 ACTIVATION UGT1A1 tetramer Reactome DB_ID: 159191 4 Reactome Database ID Release 81 159191 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159191 Reactome R-HSA-159191 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159191.1 Reactome Database ID Release 81 9704997 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9704997 Reactome Database ID Release 81 9632038 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9632038 Reactome R-HSA-9632038 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9632038.2 LEFT-TO-RIGHT 2.4.1.17 UGT1A4 transfers GlcA from UDP-GlcA to BMG to form BDG bilirubin monoglucuronide + UDP-glucuronic acid => bilirubin diglucuronide + UDP The principal conjugate of bilirubin in bile is bilirubin diglucuronide (BDG). UGT1A4 can transfer glucuronic acid (GlcA) to bilirubin (BIL) and bilirubin monoglucuronide (BMG) to form both the monoglucuronide and the diglucuronide (BDG) conjugates respectively (Ritter et al. 1992). Authored: Jassal, B, 2005-02-23 15:02:50 Reviewed: D'Eustachio, P, 2010-05-08 Edited: Jassal, B, 2010-05-27 ACTIVATION Reactome Database ID Release 81 159179 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159179 Reactome R-HSA-159179 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-159179.3 LEFT-TO-RIGHT 2.4.1.17 UGT1A10 transfers GlcA from UDP-GlcA to GCTN Isoflavones are a class of dietary polyphenols called phytoestrogens which are found in soy and soy foods, alfalfa sprouts and red clover. They possess biological activities ranging from anticancer to cardiovascular protective effects (Zhou et al. 2016). Despite their health claims, making these compounds into chemo-preventive or chemo-therapeutic agents is complicated by their low bioavailabilities (<5%), the result of extensive first-pass metabolism by phase II enzymes including UGTs and SULTs (Hu 2007). Four UDP-glucuronosyltransferase 1A (UGT1A) isoforms share the responsibility of metabolising various isoflavones. UGT1A10 is mainly expressed in the intestine and is located on the ER membrane of these cells. It can transfer the glucuronyl moiety from UDP-GlcA to the isoflavone glycitein (GCTN) to form glycitein 4-O-glucuronide (GCTN4OG) (Tang et al. 2009). Authored: Jassal, Bijay, 2016-10-06 Reviewed: D'Eustachio, Peter, 2017-01-06 Edited: Jassal, Bijay, 2016-10-06 GCTN glycitein Reactome DB_ID: 8941723 glycitein [ChEBI:34778] glycitein 7-hydroxy-3-(4-hydroxyphenyl)-6-methoxychromen-4H-one InChI=1S/C16H12O5/c1-20-15-6-11-14(7-13(15)18)21-8-12(16(11)19)9-2-4-10(17)5-3-9/h2-8,17-18H,1H3 C16H12O5 7,4'-Dihydroxy-6-methoxyisoflavone 7-hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one COc1cc2c(cc1O)occ(-c1ccc(O)cc1)c2=O DXYUAIFZCFRPTH-UHFFFAOYSA-N 7-Hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-1-benzopyran-4-one ChEBI CHEBI:34778 Reactome Database ID Release 81 8941723 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941723 Reactome R-ALL-8941723 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-8941723.3 GCTN4OG glycitein 4-O-glucuronide glycitein 4'-O-glucuronide Reactome DB_ID: 8941725 glycitein 4'-O-glucuronide [ChEBI:133667] glycitein 4'-O-glucuronide ChEBI CHEBI:133667 Reactome Database ID Release 81 8941725 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941725 Reactome R-ALL-8941725 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-8941725.3 ACTIVATION UGT1A10 UDP-glucuronosyltransferase 1-10 UD110_HUMAN Reactome DB_ID: 8933307 UniProt:Q9HAW8 UGT1A10 UGT1A10 GNT1 UGT1 SUBUNIT Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A9 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A9 (PubMed:20610558).TISSUE SPECIFICITY Liver and colon (PubMed:9271343). Isoform 1 and isoform 2 are expressed in colon, esophagus and small intestine; isoform 2 but not isoform 1 is expressed in liver or kidney (PubMed:18004212).MISCELLANEOUS UGT1A10 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.SIMILARITY Belongs to the UDP-glycosyltransferase family. UniProt Q9HAW8 26 EQUAL 530 EQUAL Reactome Database ID Release 81 8933307 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8933307 Reactome R-HSA-8933307 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8933307.1 Reactome Database ID Release 81 8941722 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941722 Reactome Database ID Release 81 8941701 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=8941701 Reactome R-HSA-8941701 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-8941701.1 19545173 Pubmed 2009 Structure and concentration changes affect characterization of UGT isoform-specific metabolism of isoflavones Tang, Lan Singh, Rashim Liu, Zhongqiu Hu, Ming Mol. Pharm. 6:1466-82 18052085 Pubmed 2007 Commentary: bioavailability of flavonoids and polyphenols: call to arms Hu, Ming Mol. Pharm. 4:803-6 27556486 Pubmed 2016 Natural Polyphenols for Prevention and Treatment of Cancer Zhou, Yue Zheng, J Li, Ya Xu, Dong-Ping Li, Sha Chen, Yu-Ming Li, Hua-Bin Nutrients 8: LEFT-TO-RIGHT 2.4.1.17 Formation of N-glucuronides Typical N-centred substrates were chosen as examples for these isozymes. Reviewed: D'Eustachio, P, 2008-05-28 08:30:54 Converted from EntitySet in Reactome N-centre functional group substrate Reactome DB_ID: 174932 TAM tamoxifen Reactome DB_ID: 159154 tamoxifen [ChEBI:41774] tamoxifen ChEBI CHEBI:41774 Reactome Database ID Release 81 159154 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159154 Reactome R-ALL-159154 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159154.3 COMPOUND C07108 Nicotine (S)-3-(1-methylpyrrolidin-2-yl)pyridine (S)-nicotine Reactome DB_ID: 30661 (S)-nicotine [ChEBI:17688] (S)-nicotine ChEBI CHEBI:17688 Reactome Database ID Release 81 30661 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30661 Reactome R-ALL-30661 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30661.3 COMPOUND C00745 Reactome Database ID Release 81 174932 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174932 Reactome R-ALL-174932 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174932.1 Converted from EntitySet in Reactome N-glucuronide Reactome DB_ID: 174918 TAMNG Tamoxifen N-glucuronide tamoxifen N-beta-D-glucosiduronic acid Reactome DB_ID: 159189 tamoxifen N-beta-D-glucosiduronic acid [ChEBI:32663] tamoxifen N-beta-D-glucosiduronic acid ChEBI CHEBI:32663 Reactome Database ID Release 81 159189 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159189 Reactome R-ALL-159189 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159189.3 Nicotine N-glucuronide (S)-nicotinium N-alpha-D-glucosiduronate Reactome DB_ID: 159298 (S)-nicotinium N-alpha-D-glucosiduronate [ChEBI:63860] (S)-nicotinium N-alpha-D-glucosiduronate Nicotine glucuronide nicotine N-glucuronide 3,4,5-trihydroxy-6-[5-(1-methylpyrrolidin-2-yl)pyridin-1-yl]-oxane-2-carboxylate (S)-1-alpha-D-glucopyranuronosyl-3-(1-methyl-2-pyrrolidinyl)pyridinium inner salt ChEBI CHEBI:63860 Reactome Database ID Release 81 159298 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=159298 Reactome R-ALL-159298 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-159298.3 Reactome Database ID Release 81 174918 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174918 Reactome R-ALL-174918 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174918.1 ACTIVATION Converted from EntitySet in Reactome UGT1A3,A4,A9 UDP-glucuronosyltransferase (N-glucuronide forming isozymes) Reactome DB_ID: 174917 Reactome Database ID Release 81 174917 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174917 Reactome R-HSA-174917 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174917.2 Reactome Database ID Release 81 174934 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174934 Reactome Database ID Release 81 174916 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174916 Reactome R-HSA-174916 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-174916.2 14570768 Pubmed 2003 N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases Kuehl, GE Murphy, SE Drug Metab Dispos 31:1361-8 12433823 Pubmed 2002 Characterization of nicotine and cotinine N-glucuronidations in human liver microsomes Nakajima, M Tanaka, E Kwon, JT Yokoi, T Drug Metab Dispos 30:1484-90 15135306 Pubmed 2004 Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4 Kaku, T Ogura, K Nishiyama, T Ohnuma, T Muro, K Hiratsuka, A Biochem Pharmacol 67:2093-102 LEFT-TO-RIGHT 3.2.1 ABHD10 hydrolyses MPAG Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant drug mycophenolate mofetil (MMF) and is primarily metabolised by glucuronidation to a phenolic glucuronide (MPAG) and an acyl glucuronide (AMPAG), a potential immunotoxic metabolite. Mitochondrial mycophenolic acid acyl-glucuronide esterase (ABHD10) deglucuronidates AMPAG thereby ABHD10 could play a role in the protection against acyl glucuronide-induced toxicity (Iwamura et al. 2012). Authored: Jassal, Bijay, 2015-05-22 Reviewed: D'Eustachio, Peter, 2015-06-26 Edited: Jassal, Bijay, 2015-05-22 H2O water Reactome DB_ID: 113521 mitochondrial matrix GENE ONTOLOGY GO:0005759 Reactome Database ID Release 81 113521 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113521 Reactome R-ALL-113521 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113521.3 COMPOUND C00001 AMPAG mycophenolic acid O-acyl-glucuronide Reactome DB_ID: 5694574 mycophenolic acid O-acyl-glucuronide [ChEBI:64689] mycophenolic acid O-acyl-glucuronide mycophenolic acid-O-acyl-beta-D-glucopyranuronoside mycophenolic acid acyl glucuronide AcMPAG mycophenolic acid acyl-glucuronide ChEBI CHEBI:64689 Reactome Database ID Release 81 5694574 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694574 Reactome R-ALL-5694574 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-5694574.3 GlcA D-glucuronic acid D-glucuronate Reactome DB_ID: 5694569 D-glucuronate [ChEBI:15748] D-glucuronate Glucuronate ChEBI CHEBI:15748 Reactome Database ID Release 81 5694569 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694569 Reactome R-ALL-5694569 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-5694569.3 MPA mycophenolic acid Reactome DB_ID: 5694565 mycophenolate [ChEBI:62932] mycophenolate (4E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoate ChEBI CHEBI:62932 Reactome Database ID Release 81 5694565 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694565 Reactome R-ALL-5694565 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-5694565.4 ACTIVATION ABHD10 Mycophenolic acid acyl-glucuronide esterase, mitochondrial ecNumber3.1.1.93/ecNumber ABHDA_HUMAN Reactome DB_ID: 5694577 UniProt:Q9NUJ1 ABHD10 ABHD10 FUNCTION Acts as an acyl-protein thioesterase that hydrolyzes fatty acids from acylated residues in proteins (PubMed:31740833). Regulates the mitochondrial S-depalmitoylation of the nucleophilic active site residue of peroxiredoxin-5/PRDX5, a key antioxidant protein, therefore modulating mitochondrial antioxidant ability (PubMed:31740833). Also catalyzes the deglucuronidation of mycophenolic acid acyl-glucuronide, an active metabolite of the immunosuppressant drug mycophenolate (PubMed:22294686).ACTIVITY REGULATION Inhibited by palmostatin-B.SIMILARITY Belongs to the AB hydrolase superfamily. UniProt Q9NUJ1 53 EQUAL 306 EQUAL Reactome Database ID Release 81 5694577 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694577 Reactome R-HSA-5694577 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5694577.1 GENE ONTOLOGY GO:0004553 Reactome Database ID Release 81 5694578 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694578 Reactome Database ID Release 81 5694563 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5694563 Reactome R-HSA-5694563 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-5694563.1 22294686 Pubmed 2012 Human α/β hydrolase domain containing 10 (ABHD10) is responsible enzyme for deglucuronidation of mycophenolic acid acyl-glucuronide in liver Iwamura, Atsushi Fukami, Tatsuki Higuchi, Ryota Nakajima, Miki Yokoi, Tsuyoshi J. Biol. Chem. 287:9240-9 Reactome Database ID Release 81 156588 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=156588 Reactome R-HSA-156588 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-156588.3 14977861 Pubmed 2004 Glucuronidation and the UDP-glucuronosyltransferases in health and disease Wells, PG Mackenzie, PI Chowdhury, JR Guillemette, C Gregory, PA Ishii, Y Hansen, AJ Kessler, FK Kim, PM Chowdhury, NR Ritter, JK Drug Metab Dispos 32:281-90 10836148 Pubmed 2000 Human UDP-glucuronosyltransferases: metabolism, expression, and disease Tukey, RH Strassburg, CP Annu Rev Pharmacol Toxicol 40:581-616 GENE ONTOLOGY GO:0052695