UD11_MOUSE
ID UD11_MOUSE Reviewed; 535 AA.
AC Q63886; Q561M6; Q6XL50;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=UDP-glucuronosyltransferase 1A1 {ECO:0000305};
DE Short=UGT1A1;
DE EC=2.4.1.17 {ECO:0000250|UniProtKB:P22309};
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 AltName: Full=UGTBR1;
DE Flags: Precursor;
GN Name=Ugt1a1 {ECO:0000312|MGI:MGI:98898}; Synonyms=Ugt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8464825; DOI=10.1023/a:1018965011846;
RA Kong A.N., Ma M., Tao D., Yang L.;
RT "Molecular cloning of two cDNAs encoding the mouse bilirubin/phenol family
RT of UDP-glucuronosyltransferases (mUGTBr/p).";
RL Pharm. Res. 10:461-465(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Colon;
RX PubMed=14672974; DOI=10.1101/gr.1225204;
RA Zhang T., Haws P., Wu Q.;
RT "Multiple variable first exons: a mechanism for cell- and tissue-specific
RT gene regulation.";
RL Genome Res. 14:79-89(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity). Essential for the elimination and detoxification
CC of drugs, xenobiotics and endogenous compounds (By similarity).
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:Q64550}.
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=Q63886-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver and at lower levels in
CC colon, kidney, stomach and intestine. {ECO:0000269|PubMed:14672974}.
CC -!- INDUCTION: By dioxin.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; S64760; AAB26033.2; -; mRNA.
DR EMBL; AY227194; AAP48593.1; -; mRNA.
DR EMBL; BC093516; AAH93516.1; -; mRNA.
DR CCDS; CCDS15143.1; -. [Q63886-1]
DR RefSeq; NP_964007.2; NM_201645.2. [Q63886-1]
DR AlphaFoldDB; Q63886; -.
DR SMR; Q63886; -.
DR STRING; 10090.ENSMUSP00000072803; -.
DR ChEMBL; CHEMBL4523337; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyGen; Q63886; 3 sites.
DR iPTMnet; Q63886; -.
DR PhosphoSitePlus; Q63886; -.
DR SwissPalm; Q63886; -.
DR jPOST; Q63886; -.
DR MaxQB; Q63886; -.
DR PaxDb; Q63886; -.
DR PeptideAtlas; Q63886; -.
DR PRIDE; Q63886; -.
DR ProteomicsDB; 298192; -. [Q63886-1]
DR Antibodypedia; 35061; 235 antibodies from 27 providers.
DR DNASU; 394436; -.
DR Ensembl; ENSMUST00000073049; ENSMUSP00000072803; ENSMUSG00000089960. [Q63886-1]
DR GeneID; 394436; -.
DR KEGG; mmu:394436; -.
DR UCSC; uc007byk.1; mouse. [Q63886-1]
DR CTD; 54658; -.
DR MGI; MGI:98898; Ugt1a1.
DR VEuPathDB; HostDB:ENSMUSG00000089960; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000159677; -.
DR HOGENOM; CLU_012949_3_0_1; -.
DR InParanoid; Q63886; -.
DR OMA; AKVFMTH; -.
DR OrthoDB; 508327at2759; -.
DR PhylomeDB; Q63886; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 3474.
DR Reactome; R-MMU-156588; Glucuronidation.
DR Reactome; R-MMU-189483; Heme degradation.
DR Reactome; R-MMU-9749641; Aspirin ADME.
DR Reactome; R-MMU-9753281; Paracetamol ADME.
DR BioGRID-ORCS; 394436; 15 hits in 76 CRISPR screens.
DR PRO; PR:Q63886; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q63886; protein.
DR Bgee; ENSMUSG00000089960; Expressed in duodenum and 47 other tissues.
DR Genevisible; Q63886; MM.
DR GO; GO:0070069; C:cytochrome complex; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:MGI.
DR GO; GO:0015020; F:glucuronosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; ISO:MGI.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0070980; P:biphenyl catabolic process; ISO:MGI.
DR GO; GO:0052695; P:cellular glucuronidation; ISS:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl.
DR GO; GO:0008210; P:estrogen metabolic process; ISS:UniProtKB.
DR GO; GO:0051552; P:flavone metabolic process; ISO:MGI.
DR GO; GO:0052696; P:flavonoid glucuronidation; ISO:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:2001030; P:negative regulation of cellular glucuronidation; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR GO; GO:0052697; P:xenobiotic glucuronidation; ISS:UniProtKB.
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; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lipid metabolism; Membrane; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..535
FT /note="UDP-glucuronosyltransferase 1A1"
FT /id="PRO_0000036010"
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 25
FT /note="S -> Y (in Ref. 1; AAB26033)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="L -> I (in Ref. 1; AAB26033)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="H -> R (in Ref. 2; AAP48593)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 535 AA; 60047 MW; 8C938AFD2D6DEB1D CRC64;
MTVVCWSSRL LLLLPYLLLC VFGPSASHAG RLLVFPMDGS HWLSMLGVIQ QLQQKGHEVV
VIAPEASIHI KEGSFYTLRK FPVPFQKENV TATLVELGRT AFNQDSFLLR VVKIYMKVKR
DSSMLLAGCS HLLHNAEFMA SLEESHFDAL LTDPFLPCGS IVAQYLTVPT VYFLNKLPCS
LDSEATQCPV PLSYVPKSLS FNSDRMNFLQ RVKNVLLAVS ENFMCRVVYS PYGSLATEIL
QKEVTVQDLL SPASIWLMRS DFVKDYPRPI MPNMVFIGGI NCLQKKPLSQ EFEAYVNASG
EHGIVVFSLG SMVSEIPEKK AMEIAEALGR IPQTVLWRYT GTRPSNLAKN TILVKWLPQN
DLLGHPKTRA FITHSGSHGI YEGICNGVPM VMMPLFGDQM DNAKRMETRG AGVTLNVLEM
TADDLENALK TVINNKSYKE NIMRLSSLHK DRPIEPLDLA VFWVEYVMRH KGAPHLRPAA
HDLTWYQYHS LDVIGFLLAI VLTVVFIVFK CCAYGCRKCF GGKGRVKKSH KSKTH
