UD11_RAT
ID UD11_RAT Reviewed; 535 AA.
AC Q64550; Q64635;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=UDP-glucuronosyltransferase 1A1 {ECO:0000305};
DE Short=UGT1A1;
DE EC=2.4.1.17 {ECO:0000250|UniProtKB:P22309};
DE AltName: Full=B1;
DE AltName: Full=UDP-glucuronosyltransferase 1-1;
DE Short=UDPGT 1-1;
DE Short=UGT1*1;
DE Short=UGT1-01;
DE Short=UGT1.1;
DE Flags: Precursor;
GN Name=Ugt1a1 {ECO:0000312|RGD:3935}; Synonyms=Ugt1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Wistar;
RX PubMed=7603447;
RA Coffman B.L., Green M.D., King C.O., Tephly T.R.;
RT "Cloning and stable expression of a cDNA encoding a rat liver UDP-
RT glucuronosyltransferase (UDP-glucuronosyltransferase 1.1) that catalyzes
RT the glucuronidation of opioids and bilirubin.";
RL Mol. Pharmacol. 47:1101-1105(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-290.
RC STRAIN=Wistar;
RX PubMed=7608130; DOI=10.1093/jb/117.2.392;
RA Emi Y., Ikushiro S., Iyanagi T.;
RT "Drug-responsive and tissue-specific alternative expression of multiple
RT first exons in rat UDP-glucuronosyltransferase family 1 (UGT1) gene
RT complex.";
RL J. Biochem. 117:392-399(1995).
RN [3]
RP PROTEIN SEQUENCE OF 30-41.
RX PubMed=7986077; DOI=10.1006/abbi.1994.1510;
RA Ishii Y., Tsuruda K., Tanaka M., Oguri K.;
RT "Purification of a phenobarbital-inducible morphine UDP-
RT glucuronyltransferase isoform, absent from Gunn rat liver.";
RL Arch. Biochem. Biophys. 315:345-351(1994).
RN [4]
RP FUNCTION, AND INDUCTION BY 3-METHYLCHOLANTHRENE.
RX PubMed=8554318; DOI=10.1006/abbi.1995.0039;
RA Ikushiro S., Emi Y., Iyanagi T.;
RT "Identification and analysis of drug-responsive expression of UDP-
RT glucuronosyltransferase family 1 (UGT1) isozyme in rat hepatic microsomes
RT using anti-peptide antibodies.";
RL Arch. Biochem. Biophys. 324:267-272(1995).
CC -!- FUNCTION: UDP-glucuronosyltransferase (UGT) that catalyzes phase II
CC biotransformation reactions in which lipophilic substrates are
CC conjugated with glucuronic acid to increase the metabolite's water
CC solubility, thereby facilitating excretion into either the urine or
CC bile (PubMed:8554318). Essential for the elimination and detoxification
CC of drugs, xenobiotics and endogenous compounds (PubMed:8554318).
CC Catalyzes the glucuronidation of endogenous estrogen hormones such as
CC estradiol, estrone and estriol (By similarity). Involved in the
CC glucuronidation of bilirubin, a degradation product occurring in the
CC normal catabolic pathway that breaks down heme in vertebrates (By
CC similarity). Also catalyzes the glucuronidation the isoflavones
CC genistein, daidzein, glycitein, formononetin, biochanin A and prunetin,
CC which are phytoestrogens with anticancer and cardiovascular properties
CC (By similarity). Involved in the glucuronidation of the AGTR1
CC angiotensin receptor antagonist losartan, a drug which can inhibit the
CC effect of angiotensin II (By similarity). Involved in the
CC biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the
CC pharmacologically active metabolite of the anticancer drug irinotecan
CC (By similarity). {ECO:0000250|UniProtKB:P22309,
CC ECO:0000269|PubMed:8554318}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor
CC beta-D-glucuronoside + H(+) + UDP; Xref=Rhea:RHEA:21032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132367, ChEBI:CHEBI:132368; EC=2.4.1.17;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52460,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136641;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52461;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxyestrone + UDP-alpha-D-glucuronate = 2-hydroxyestrone
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:53048,
CC ChEBI:CHEBI:1156, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136967;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53049;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hydroxy-17beta-estradiol + UDP-alpha-D-glucuronate = 2-
CC hydroxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53004, ChEBI:CHEBI:15378, ChEBI:CHEBI:28744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136931;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53005;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methoxy-17beta-estradiol + UDP-alpha-D-glucuronate = 2-
CC methoxy-17beta-estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:53072, ChEBI:CHEBI:15378, ChEBI:CHEBI:28955,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136974;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53073;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-
CC estradiol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52868, ChEBI:CHEBI:15378, ChEBI:CHEBI:17160,
CC ChEBI:CHEBI:57529, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16beta,17beta-estriol + UDP-alpha-D-glucuronate =
CC 16beta,17beta-estriol 16-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52880, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:87620, ChEBI:CHEBI:136886;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52881;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=losartan + UDP-alpha-D-glucuronate = losartan-2-N-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63720, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149504, ChEBI:CHEBI:149507;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63721;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prunetin + UDP-alpha-D-glucuronate = prunetin-4'-O-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63588, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:147403, ChEBI:CHEBI:147404;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63589;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=SN-38 + UDP-alpha-D-glucuronate = H(+) + SN-38 O-beta-D-
CC glucuronide + UDP; Xref=Rhea:RHEA:63696, ChEBI:CHEBI:8988,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:149482; Evidence={ECO:0000250|UniProtKB:P22309};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63697;
CC Evidence={ECO:0000250|UniProtKB:P22309};
CC -!- SUBUNIT: Homodimers. Homooligomer. Interacts with UGT1A3, UGT1A4,
CC UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers.
CC {ECO:0000250|UniProtKB:P22309}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P22309}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=UGT1A1 is one of the isoforms produced at the UGT1A complex
CC locus. The UGT1A complex locus produces different isoforms based on
CC alternative use of promoters, first exons and terminal exons.
CC {ECO:0000250|UniProtKB:P22309};
CC Name=1;
CC IsoId=Q64550-1; Sequence=Displayed;
CC -!- INDUCTION: Induced in 3-methylcholanthrene-treated rats.
CC {ECO:0000269|PubMed:8554318}.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; U20551; AAC52219.1; -; Genomic_DNA.
DR EMBL; D38065; BAA07260.1; -; Genomic_DNA.
DR PIR; I57961; I57961.
DR RefSeq; NP_036815.1; NM_012683.2. [Q64550-1]
DR AlphaFoldDB; Q64550; -.
DR SMR; Q64550; -.
DR IntAct; Q64550; 1.
DR STRING; 10116.ENSRNOP00000025045; -.
DR BindingDB; Q64550; -.
DR ChEMBL; CHEMBL4523339; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyGen; Q64550; 3 sites.
DR SwissPalm; Q64550; -.
DR PaxDb; Q64550; -.
DR PRIDE; Q64550; -.
DR Ensembl; ENSRNOT00000025045; ENSRNOP00000025045; ENSRNOG00000018740. [Q64550-1]
DR GeneID; 24861; -.
DR KEGG; rno:24861; -.
DR CTD; 54658; -.
DR RGD; 3935; Ugt1a1.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000159677; -.
DR HOGENOM; CLU_012949_3_1_1; -.
DR InParanoid; Q64550; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 5301.
DR Reactome; R-RNO-156588; Glucuronidation.
DR Reactome; R-RNO-189483; Heme degradation.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR Reactome; R-RNO-9753281; Paracetamol ADME.
DR PRO; PR:Q64550; -.
DR Proteomes; UP000002494; Chromosome 9.
DR Bgee; ENSRNOG00000018740; Expressed in duodenum and 20 other tissues.
DR ExpressionAtlas; Q64550; baseline and differential.
DR Genevisible; Q64550; RN.
DR GO; GO:0070069; C:cytochrome complex; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; IDA:RGD.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:RGD.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0001972; F:retinoic acid binding; ISO:RGD.
DR GO; GO:0005496; F:steroid binding; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0006789; P:bilirubin conjugation; TAS:RGD.
DR GO; GO:0070980; P:biphenyl catabolic process; IDA:RGD.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:RGD.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071361; P:cellular response to ethanol; IEP:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0008210; P:estrogen metabolic process; ISO:RGD.
DR GO; GO:0051552; P:flavone metabolic process; ISO:RGD.
DR GO; GO:0052696; P:flavonoid glucuronidation; IDA:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IMP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0052697; P:xenobiotic glucuronidation; IDA:RGD.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR002213; UDP_glucos_trans.
DR InterPro; IPR035595; UDP_glycos_trans_CS.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Lipid metabolism; Membrane;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:7986077"
FT CHAIN 30..535
FT /note="UDP-glucuronosyltransferase 1A1"
FT /id="PRO_0000036011"
FT TRANSMEM 493..509
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 253
FT /note="A -> D (in Ref. 2; BAA07260)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 59663 MW; 26B642FCA7DD4082 CRC64;
MSVVCRSSCS LLLLPCLLLC VLGPSASHAG KLLVIPIDGS HWLSMLGVIQ QLQQKGHEVV
VIAPEASIHI KEGSFYTMRK YPVPFQNENV TAAFVELGRS VFDQDPFLLR VVKTYNKVKR
DSSMLLSGCS HLLHNAEFMA SLEQSHFDAL LTDPFLPCGS IVAQYLSLPA VYFLNALPCS
LDLEATQCPA PLSYVPKSLS SNTDRMNFLQ RVKNMIIALT ENFLCRVVYS PYGSLATEIL
QKEVTVKDLL SPASIWLMRN DFVKDYPRPI MPNMVFIGGI NCLQKKALSQ EFEAYVNASG
EHGIVVFSLG SMVSEIPEKK AMEIAEALGR IPQTVLWRYT GTRPSNLAKN TILVKWLPQN
DLLGHPKARA FITHSGSHGI YEGICNGVPM VMMPLFGDQM DNAKRMETRG AGVTLNVLEM
TADDLENALK TVINNKSYKE NIMRLSSLHK DRPIEPLDLA VFWVEYVMRH KGAPHLRPAA
HDLTWYQYHS LDVIGFLLAI VLTVVFIVYK SCAYGCRKCF GGKGRVKKSH KSKTH
