UDB15_RAT
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 03-AUG-2022, entry version 134.
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}; 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 4-
CC 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 hexafluoro-2-
CC propanol glucuronide {ECO:0000269|PubMed:7574722};
CC Vmax=330 pmol/min/mg enzyme for the formation of hexafluoro-2-
CC 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 GlyGen; P36511; 1 site.
DR iPTMnet; P36511; -.
DR PhosphoSitePlus; P36511; -.
DR PaxDb; P36511; -.
DR PRIDE; P36511; -.
DR UCSC; RGD:620895; rat.
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 PRO; PR:P36511; -.
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:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
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 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 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
