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   13-SEP-2023, entry version 154.
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   GeneID; 266685; -.
DR   KEGG; rno:266685; -.
DR   UCSC; RGD:628623; rat.
DR   AGR; RGD:628623; -.
DR   CTD; 7366; -.
DR   RGD; 628623; Ugt2b5.
DR   InParanoid; P08542; -.
DR   OrthoDB; 382054at2759; -.
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   Reactome; R-RNO-9757110; Prednisone ADME.
DR   PRO; PR:P08542; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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   Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2.
DR   InterPro; IPR002213; UDP_glucos_trans.
DR   InterPro; IPR035595; UDP_glycos_trans_CS.
DR   PANTHER; PTHR48043; EG:EG0003.4 PROTEIN-RELATED; 1.
DR   PANTHER; PTHR48043:SF113; UDP GLUCURONOSYLTRANSFERASE 2 FAMILY, POLYPEPTIDE B38-RELATED; 1.
DR   Pfam; PF00201; UDPGT; 1.
DR   SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 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
//