ID   UDB15_RAT               Reviewed;         530 AA.
AC   P36511;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   08-NOV-2023, entry version 139.
DE   RecName: Full=UDP-glucuronosyltransferase 2B15 {ECO:0000305};
DE            Short=UDPGT 2B15;
DE            Short=UGT2B15;
DE            EC=2.4.1.17 {ECO:0000269|PubMed:7574722};
DE   AltName: Full=UDP-glucuronosyltransferase 2B36;
DE            Short=UDPGT 2B36;
DE   Flags: Precursor;
GN   Name=Ugt2b15 {ECO:0000312|RGD:620895};
GN   Synonyms=Ugt2b12, Ugt2b36, Ugt2b4;
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], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND INDUCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=7574722; DOI=10.1006/abbi.1995.1489;
RA   Green M.D., Clarke D.J., Oturu E.M., Styczynski P.B., Jackson M.R.,
RA   Burchell B., Tephly T.R.;
RT   "Cloning and expression of a rat liver phenobarbital-inducible UDP-
RT   glucuronosyltransferase (2B12) with specificity for monoterpenoid
RT   alcohols.";
RL   Arch. Biochem. Biophys. 322:460-468(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Kidney;
RA   Green M.D.;
RL   Submitted (FEB-1994) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 24-38, AND CHARACTERIZATION.
RC   STRAIN=Wistar; TISSUE=Liver;
RX   PubMed=1906977;
RA   Styczynski P.B., Green M.S., Puig J., Coffman B.L., Tephly T.R.;
RT   "Purification and properties of a rat liver phenobarbital-inducible 4-
RT   hydroxybiphenyl UDP-glucuronosyltransferase.";
RL   Mol. Pharmacol. 40:80-84(1991).
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:7574722). Essential for the elimination and detoxification
CC       of drugs, xenobiotics and endogenous compounds (PubMed:7574722).
CC       Catalyzes the glucuronidation of endogenous steroid hormones such as
CC       androgens (testosterone, androsterone) and estrogens (estradiol,
CC       epiestradiol, estriol, catechol estrogens) (PubMed:7574722). Displays
CC       glucuronidation activity toward several classes of xenoblotic
CC       substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-
CC       hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins)
CC       (PubMed:7574722). Catalyzes the glucuronidation of monoterpenoid
CC       alcohols such as borneol, menthol and isomenthol, a class of natural
CC       compounds used in essential oils (PubMed:7574722).
CC       {ECO:0000269|PubMed:7574722}.
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:7574722};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC         Evidence={ECO:0000269|PubMed:7574722};
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:P54855};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC         Evidence={ECO:0000250|UniProtKB:P54855};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=16alpha,17alpha-estriol + UDP-alpha-D-glucuronate =
CC         16alpha,17alpha-estriol 3-O-(beta-D-glucuronate) + H(+) + UDP;
CC         Xref=Rhea:RHEA:52924, ChEBI:CHEBI:15378, ChEBI:CHEBI:42156,
CC         ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136882;
CC         Evidence={ECO:0000250|UniProtKB:P54855};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52925;
CC         Evidence={ECO:0000250|UniProtKB:P54855};
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:P54855};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53001;
CC         Evidence={ECO:0000250|UniProtKB:P54855};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=280 uM for UDP-alpha-D-glucuronate (when assaying glucuronidation
CC         with (1S,2R,4S)-borneol and 4-nitrophenol as substrates)
CC         {ECO:0000269|PubMed:7574722};
CC         KM=330 uM for UDP-alpha-D-glucuronate (when assaying glucuronidation
CC         with (1S,2R,4S)-borneol and 4-nitrophenol as substrates)
CC         {ECO:0000269|PubMed:7574722};
CC         KM=90 uM for 4-hydroxy-estrone {ECO:0000269|PubMed:7574722};
CC         KM=140 uM for 4-hydroxy-estrone {ECO:0000269|PubMed:7574722};
CC         KM=49 uM for naringenin {ECO:0000269|PubMed:7574722};
CC         KM=55 uM for naringenin {ECO:0000269|PubMed:7574722};
CC         KM=850 uM for 4-methylumbelliferone {ECO:0000269|PubMed:7574722};
CC         KM=260 uM for eugenol {ECO:0000269|PubMed:7574722};
CC         KM=1680 uM for 4-nitrophenol {ECO:0000269|PubMed:7574722};
CC         KM=51 uM for 2-hydroxybiphenyl {ECO:0000269|PubMed:7574722};
CC         KM=35 uM for 2-hydroxybiphenyl {ECO:0000269|PubMed:7574722};
CC         KM=36 uM for (1S,2R,4S)-borneol {ECO:0000269|PubMed:7574722};
CC         KM=10 uM for (+)-menthol {ECO:0000269|PubMed:7574722};
CC         KM=50 uM for (+)-isomenthol {ECO:0000269|PubMed:7574722};
CC         KM=585 uM for hexafluoro-2-propanol {ECO:0000269|PubMed:7574722};
CC         KM=644 uM for hexafluoro-2-propanol {ECO:0000269|PubMed:7574722};
CC         Vmax=140 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=190 pmol/min/mg enzyme for the formation of 4-hydroxy-estrone
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=117 pmol/min/mg enzyme for the formation of naringenin
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=123 pmol/min/mg enzyme for the formation of naringenin
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=137 pmol/min/mg enzyme for the formation of
CC         4-methylumbelliferone glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=265 pmol/min/mg enzyme for the formation of eugenol glucuronide
CC         {ECO:0000269|PubMed:7574722};
CC         Vmax=290 pmol/min/mg enzyme for the formation of 4-nitrophenol
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=220 pmol/min/mg enzyme for the formation of 2-hydroxybiphenyl
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=150 pmol/min/mg enzyme for the formation of 2-hydroxybiphenyl
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=320 pmol/min/mg enzyme for the formation of (1S,2R,4S)-borneol
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=9 pmol/min/mg enzyme for the formation of (+)-menthol
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=110 pmol/min/mg enzyme for the formation of (+)-isomenthol
CC         glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=280 pmol/min/mg enzyme for the formation of
CC         hexafluoro-2-propanol glucuronide {ECO:0000269|PubMed:7574722};
CC         Vmax=330 pmol/min/mg enzyme for the formation of
CC         hexafluoro-2-propanol glucuronide {ECO:0000269|PubMed:7574722};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P54855}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Liver. Lower levels seen in the kidney and testis.
CC       {ECO:0000269|PubMed:7574722}.
CC   -!- INDUCTION: By phenobarbital. {ECO:0000269|PubMed:7574722}.
CC   -!- PTM: N-glycosylated. {ECO:0000305}.
CC   -!- POLYMORPHISM: The sequence shown is that of the liver isozyme. The
CC       kidney isoform differs in 12 positions. {ECO:0000269|Ref.2}.
CC   -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; U06273; AAA83404.1; -; mRNA.
DR   EMBL; U06274; AAA83405.1; -; mRNA.
DR   PIR; S68200; S68200.
DR   AlphaFoldDB; P36511; -.
DR   SMR; P36511; -.
DR   IntAct; P36511; 1.
DR   STRING; 10116.ENSRNOP00000002712; -.
DR   CAZy; GT1; Glycosyltransferase Family 1.
DR   GlyCosmos; P36511; 1 site, No reported glycans.
DR   GlyGen; P36511; 1 site.
DR   iPTMnet; P36511; -.
DR   PhosphoSitePlus; P36511; -.
DR   PaxDb; 10116-ENSRNOP00000002712; -.
DR   UCSC; RGD:620895; rat.
DR   AGR; RGD:620895; -.
DR   RGD; 620895; Ugt2b36.
DR   eggNOG; KOG1192; Eukaryota.
DR   InParanoid; P36511; -.
DR   PhylomeDB; P36511; -.
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:P36511; -.
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:0019439; P:aromatic compound catabolic process; IDA:RGD.
DR   GO; GO:0052695; P:cellular glucuronidation; ISS:UniProtKB.
DR   GO; GO:0008210; P:estrogen metabolic process; ISS:UniProtKB.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; 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:SF64; UDP-GLUCURONOSYLTRANSFERASE; 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   Direct protein sequencing; Endoplasmic reticulum; Glycoprotein;
KW   Glycosyltransferase; Lipid metabolism; Membrane; Reference proteome;
KW   Signal; Steroid metabolism; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:1906977"
FT   CHAIN           24..530
FT                   /note="UDP-glucuronosyltransferase 2B15"
FT                   /id="PRO_0000036036"
FT   TRANSMEM        494..510
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        316
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         2
FT                   /note="S -> P (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         61
FT                   /note="F -> S (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         71
FT                   /note="D -> H (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         95
FT                   /note="N -> S (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         183
FT                   /note="Q -> K (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         346
FT                   /note="P -> T (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         398
FT                   /note="A -> G (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         414..415
FT                   /note="VE -> AT (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         433
FT                   /note="V -> D (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         475
FT                   /note="K -> L (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
FT   VARIANT         488
FT                   /note="Q -> L (in kidney)"
FT                   /evidence="ECO:0000269|Ref.2"
SQ   SEQUENCE   530 AA;  61060 MW;  D49313CE3E6D5BFD CRC64;
     MSGKWISALL LLQISFCFKS GNCGKVLVWP MEYSHWMNIK IILEELVQKG HEVTVLRPSA
     FVFLDPKETS DLKFVTFPTS FSSHDLENFF TRFVNVWTYE LPRDTCLSYF LYLQDTIDEY
     SDYCLTVCKE AVSNKQFMTK LQESKFDVVF SDAIGPCGEL IAELLQIPFL YSLRFSPGYT
     IEQYIGGVLF PPSYVPMIFS GLAGQMTFIE RVHNMICMLY FDFWFQTFRE KKWDPFYSKT
     LGRPTTLAEI MGKAEMWLIR SYWDLEFPHP ISPNVDYIGG LHCKPAKPLP KDIEDFVQSS
     GEHGVVVFSL GSMVRNMTEE KANIIAWALA QIPQKVLWRF DGKKPPTLGP NTRLYKWLPQ
     NDLLGHPKTK AFVTHGGANG IYEAIHHGIP MIGIPLFAEQ HDNIAHMVAK GAAVEVNFRT
     MSKSDLLNAL EEVIDNPFYK KNAMWLSTIH HDQPTKPLDR AVFWIEFVMR HKGAKHLRSL
     GHNLPWYQYH SLDVIGFLLS CVAVTVVLAL KCFLFVYRFF VKKEKKTKNE
//