UDB17_RAT
ID UDB17_RAT Reviewed; 530 AA.
AC P08542; P16915;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=UDP-glucuronosyltransferase 2B17 {ECO:0000305};
DE Short=UDPGT 2B17;
DE Short=UGT2B17;
DE EC=2.4.1.17 {ECO:0000269|PubMed:18719240};
DE AltName: Full=17-beta-hydroxysteroid-specific UDPGT;
DE AltName: Full=RLUG38;
DE AltName: Full=Testosterone, dihydrotestosterone, and beta-estradiol-specific UDPGT;
DE AltName: Full=UDP-glucuronosyltransferase 2B5;
DE Short=UDPGT 2B5;
DE AltName: Full=UDPGTr-3;
DE Flags: Precursor;
GN Name=Ugt2b17 {ECO:0000312|RGD:628623}; Synonyms=Ugt2b3, Ugt2b5;
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 [MRNA].
RC TISSUE=Liver;
RX PubMed=3110162; DOI=10.1016/s0021-9258(18)47997-5;
RA McKenzie P.I.;
RT "Rat liver UDP-glucuronosyltransferase. Identification of cDNAs encoding
RT two enzymes which glucuronidate testosterone, dihydrotestosterone, and
RT beta-estradiol.";
RL J. Biol. Chem. 262:9744-9749(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3108864; DOI=10.1093/nar/15.9.3936;
RA Harding D., Wilson S.M., Jackson M.R., Burchell B., Green M.D.,
RA Tephly T.R.;
RT "Nucleotide and deduced amino acid sequence of rat liver 17 beta-
RT hydroxysteroid UDP-glucuronosyltransferase.";
RL Nucleic Acids Res. 15:3936-3936(1987).
RN [3]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=1692835; DOI=10.1016/s0021-9258(19)38945-8;
RA McKenzie P.I.;
RT "The cDNA sequence and expression of a variant 17 beta-hydroxysteroid UDP-
RT glucuronosyltransferase.";
RL J. Biol. Chem. 265:8699-8703(1990).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18719240; DOI=10.1124/dmd.108.022731;
RA Itaeaho K., Mackenzie P.I., Ikushiro S., Miners J.O., Finel M.;
RT "The configuration of the 17-hydroxy group variably influences the
RT glucuronidation of beta-estradiol and epiestradiol by human UDP-
RT glucuronosyltransferases.";
RL Drug Metab. Dispos. 36:2307-2315(2008).
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:18719240). Catalyzes the glucuronidation of endogenous
CC steroid hormones such as androgens (epitestosterone, androsterone) and
CC estrogens (estradiol, epiestradiol) (PubMed:18719240) (By similarity).
CC {ECO:0000250|UniProtKB:O75795, ECO:0000269|PubMed:1692835,
CC ECO:0000269|PubMed:18719240}.
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:0000269|PubMed:1692835, ECO:0000269|PubMed:18719240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:1692835, ECO:0000305|PubMed:18719240};
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:O75795};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000250|UniProtKB:O75795};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-
CC estradiol 17-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52872, ChEBI:CHEBI:15378, ChEBI:CHEBI:17160,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136642;
CC Evidence={ECO:0000269|PubMed:18719240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52873;
CC Evidence={ECO:0000305|PubMed:18719240};
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:0000269|PubMed:18719240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52465;
CC Evidence={ECO:0000305|PubMed:18719240};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + UDP-alpha-D-
CC glucuronate = 5alpha-dihydrotestosterone 17-O-(beta-D-glucuronate) +
CC H(+) + UDP; Xref=Rhea:RHEA:53000, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16330, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:136914; Evidence={ECO:0000250|UniProtKB:O75795};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53001;
CC Evidence={ECO:0000250|UniProtKB:O75795};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=testosterone + UDP-alpha-D-glucuronate = H(+) + testosterone
CC 17-O-(beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52456,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17347, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136639;
CC Evidence={ECO:0000250|UniProtKB:O75795};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52457;
CC Evidence={ECO:0000250|UniProtKB:O75795};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30.2 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=19.5 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC Vmax=8110 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=5890 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O75795}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Constitutively expressed.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; M31109; AAA41280.1; -; mRNA.
DR EMBL; Y00156; CAA68351.1; -; mRNA.
DR PIR; S07390; S07390.
DR RefSeq; NP_695226.2; NM_153314.2.
DR AlphaFoldDB; P08542; -.
DR SMR; P08542; -.
DR SwissLipids; SLP:000001700; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR iPTMnet; P08542; -.
DR PhosphoSitePlus; P08542; -.
DR PaxDb; P08542; -.
DR GeneID; 266685; -.
DR KEGG; rno:266685; -.
DR UCSC; RGD:628623; rat.
DR CTD; 7366; -.
DR RGD; 628623; Ugt2b5.
DR InParanoid; P08542; -.
DR OrthoDB; 508327at2759; -.
DR BRENDA; 2.4.1.17; 5301.
DR Reactome; R-RNO-156588; Glucuronidation.
DR Reactome; R-RNO-9749641; Aspirin ADME.
DR Reactome; R-RNO-9753281; Paracetamol ADME.
DR PRO; PR:P08542; -.
DR Proteomes; UP000002494; Unplaced.
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:0015020; F:glucuronosyltransferase activity; IDA:RGD.
DR GO; GO:0052695; P:cellular glucuronidation; ISS:UniProtKB.
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:0071378; P:cellular response to growth hormone stimulus; IEP:RGD.
DR GO; GO:0071394; P:cellular response to testosterone stimulus; IEP:RGD.
DR GO; GO:0008210; P:estrogen metabolic process; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP: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 Endoplasmic reticulum; Glycosyltransferase; Lipid metabolism; Membrane;
KW Reference proteome; Signal; Steroid metabolism; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000250"
FT CHAIN 24..530
FT /note="UDP-glucuronosyltransferase 2B17"
FT /id="PRO_0000036027"
FT TRANSMEM 494..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CONFLICT 54
FT /note="T -> S (in Ref. 2; CAA68351)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="G -> E (in Ref. 2; CAA68351)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="S -> G (in Ref. 2; CAA68351)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="S -> T (in Ref. 2; CAA68351)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="T -> S (in Ref. 2; CAA68351)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 60525 MW; BB633D70DBF8A7E4 CRC64;
MPGKWISALL LLQISCCFQS GNCGKVLVWP MEFSHWMNIK TILDELVQRG HEVTVLKPSA
YYVLDPKKSP DLKFETFPTS VSKDELENYF IKLVDVWTYE LQRDTCLSYS PLLQNMIDGF
SDYYLSLCKD TVSNKQLMAK LQESKFDVLL SDPVAACGEL IAEVLHIPFL YSLRFSPGYK
IEKSSGRFIL PPSYVPVILS GMGGPMTFID RVKNMICTLY FDFWFHMFNA KKWDPFYSEI
LGRPTTLAET MGKAEMWLIR SYWDLEFPHP TLPNVDYIGG LQCRPPKPLP KDMEDFVQSS
GEHGVVVFSL GSMVSSMTEE KANAIAWALA QIPQKVLWKF DGKTPATLGP NTRVYKWLPQ
NDLLGHPKTK AFVTHSGANG VYEAIYHGIP MVGIPMFGEQ HDNIAHMVAK GAAVTLNIRT
MSKSDLFNAL KEIINNPFYK KNAVWLSTIH HDQPMKPLDK AVFWIEFVMR HKGAKHLRPL
GHDLPWYQYH SLDVIGFLLT CSAVIAVLTV KCFLFIYRLF VKKEKKMKNE
