UD13_RAT
ID UD13_RAT Reviewed; 531 AA.
AC Q64637;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=UDP-glucuronosyltransferase 1A3 {ECO:0000305};
DE Short=UGT1A3;
DE EC=2.4.1.17 {ECO:0000250|UniProtKB:P35503};
DE AltName: Full=B3;
DE AltName: Full=UDP-glucuronosyltransferase 1-3;
DE Short=UDPGT 1-3;
DE Short=UGT1*3;
DE Short=UGT1-03;
DE Short=UGT1.3;
DE Flags: Precursor;
GN Name=Ugt1a3 {ECO:0000312|RGD:1549728}; 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] OF 1-286.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 287-531.
RC TISSUE=Liver;
RX PubMed=2112380; DOI=10.1016/0006-291x(90)91462-2;
RA Sato H., Koiwai O., Tanabe K., Kashiwamata S.;
RT "Isolation and sequencing of rat liver bilirubin UDP-
RT glucuronosyltransferase cDNA: possible alternate splicing of a common
RT primary transcript.";
RL Biochem. Biophys. Res. Commun. 169:260-264(1990).
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. Essential for the elimination and detoxification of drugs,
CC xenobiotics and endogenous compounds. Catalyzes the glucuronidation of
CC endogenous estrogen hormones such as estradiol and estrone. Contributes
CC to bile acid (BA) detoxification by catalyzing the glucuronidation of
CC BA substrates, which are natural detergents for dietary lipids
CC absorption. Involved in the glucuronidation of calcidiol, which is the
CC major circulating form of vitamin D3, essential for the regulation of
CC calcium and phosphate homeostasis. Involved in the glucuronidation of
CC the AGTR1 angiotensin receptor antagonists losartan, candesartan and
CC zolarsartan, which can inhibit the effect of angiotensin II.
CC {ECO:0000250|UniProtKB:P35503}.
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:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000250|UniProtKB:P35503};
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:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52461;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol
CC 17-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52464,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:82961;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52465;
CC Evidence={ECO:0000250|UniProtKB:P35503};
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:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + UDP-alpha-D-glucuronate = estrone 3-O-(beta-D-
CC glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52476, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136634; Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52477;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + UDP-alpha-D-glucuronate =
CC chenodeoxycholoyl-24-O-(beta-D-glucuronate) + UDP;
CC Xref=Rhea:RHEA:52940, ChEBI:CHEBI:36234, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136899;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52941;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholate + UDP-alpha-D-glucuronate = deoxycholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52948, ChEBI:CHEBI:23614,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136901;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52949;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + UDP-alpha-D-glucuronate = lithocholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52952, ChEBI:CHEBI:29744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136902;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52953;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyodeoxycholate + UDP-alpha-D-glucuronate = hyodeoxycholoyl-
CC 24-O-(beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52956,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:58875,
CC ChEBI:CHEBI:136903; Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52957;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyocholate + UDP-alpha-D-glucuronate = hyocholoyl-24-O-(beta-
CC D-glucuronate) + UDP; Xref=Rhea:RHEA:52960, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:133661, ChEBI:CHEBI:136904;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52961;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calcidiol + UDP-alpha-D-glucuronate = calcidiol 25-O-(beta-D-
CC glucuronide) + H(+) + UDP; Xref=Rhea:RHEA:55840, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17933, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:139277; Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55841;
CC Evidence={ECO:0000250|UniProtKB:P35503};
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:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63721;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=candesartan + UDP-alpha-D-glucuronate = candesartan-2-N-beta-
CC D-glucuronide + UDP; Xref=Rhea:RHEA:63728, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149509, ChEBI:CHEBI:149523;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63729;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UDP-alpha-D-glucuronate + zolasartan = UDP + zolarsartan-2-N-
CC beta-D-glucuronide; Xref=Rhea:RHEA:63748, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149524, ChEBI:CHEBI:149528;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63749;
CC Evidence={ECO:0000250|UniProtKB:P35503};
CC -!- SUBUNIT: Homodimers. Homooligomer. Interacts with UGT1A1, UGT1A4,
CC UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers.
CC {ECO:0000250|UniProtKB:P35503}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P22309, ECO:0000250|UniProtKB:P35503}; Single-
CC pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=UGT1A3 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:P35503};
CC Name=1;
CC IsoId=Q64637-1; Sequence=Displayed;
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; D38067; BAA07262.1; -; Genomic_DNA.
DR EMBL; M34007; AAA42312.1; ALT_TERM; mRNA.
DR AlphaFoldDB; Q64637; -.
DR SMR; Q64637; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyGen; Q64637; 4 sites.
DR RGD; 1549728; Ugt1a3.
DR InParanoid; Q64637; -.
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-9754706; Atorvastatin ADME.
DR PRO; PR:Q64637; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IBA:GO_Central.
DR GO; GO:0015020; F:glucuronosyltransferase activity; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:0052695; P:cellular glucuronidation; ISS:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; ISS:UniProtKB.
DR GO; GO:0070640; P:vitamin D3 metabolic process; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lipid metabolism; Membrane; Reference proteome;
KW Signal; Transferase; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..531
FT /note="UDP-glucuronosyltransferase 1A3"
FT /id="PRO_0000036014"
FT TRANSMEM 489..505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 293
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 531 AA; 60140 MW; ECB0994C6A2C7CEF CRC64;
MGIQGFLQKL SGLLLLLCAL PWAEGGKVLV FPMEGSHWLS IRDVVRELHA RGHQAVVLAP
EVTVHIKEED FFTLQTYPVP YTKEEYRHHL LGHLQNFFET EFSLKLVLQT MAAVNNVSTF
YVRSCRGLLH NTALIQSLNS SSFDVVLTDP FFPCGAVLAM YLRVPAVFFL QSMLCELEFE
ATNSPNPSSY IPRLLTLNSD HMSFLDRVKN MLYPVPWMYL CHVNYGSLAR LASDLLQREV
SVVEILRHAS VWLLRKDFVF HYPRPFMPNM VFIGGINCAN RKPLSQEFEA YVNASGEHGI
VVFSLGSMVS EIPEKKAMEI AEALGRIPQT LLWRYTGTRP SNLAKNTILV KWLPQNDLLG
HPKARAFITH SGSHGIYEGI CNGVPMVMMP LFGDQMDNAK RMETRGAGVT LNVLEMTADD
LENALKTVIN NKSYKENIMR LSSLHKDRPI EPLDLAVFWV EYVMRHKGAP HLRPAAHDLT
WYQYHSLDVI GFLLAIVLTV VFIVYKSCAY GCRKCFGGKG RVKKSHKSKT H
