UDB17_HUMAN
ID UDB17_HUMAN Reviewed; 530 AA.
AC O75795;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=UDP-glucuronosyltransferase 2B17 {ECO:0000303|PubMed:18719240};
DE Short=UDPGT 2B17;
DE Short=UGT2B17;
DE EC=2.4.1.17 {ECO:0000269|PubMed:16595710, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:8798464};
DE AltName: Full=C19-steroid-specific UDP-glucuronosyltransferase;
DE Short=C19-steroid-specific UDPGT;
DE Flags: Precursor;
GN Name=UGT2B17 {ECO:0000312|HGNC:HGNC:12547};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Prostate;
RX PubMed=8798464; DOI=10.1074/jbc.271.37.22855;
RA Beaulieu M., Levesque E., Hum D.W., Belanger A.;
RT "Isolation and characterization of a novel cDNA encoding a human UDP-
RT glucuronosyltransferase active on C19 steroids.";
RL J. Biol. Chem. 271:22855-22862(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9364925; DOI=10.1089/dna.1997.16.1143;
RA Beaulieu M., Levesque E., Tchernof A., Beatty B.G., Belanger A., Hum D.W.;
RT "Chromosomal localization, structure, and regulation of the UGT2B17 gene,
RT encoding a C19 steroid metabolizing enzyme.";
RL DNA Cell Biol. 16:1143-1154(1997).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=16595710; DOI=10.1124/dmd.106.009621;
RA Murai T., Samata N., Iwabuchi H., Ikeda T.;
RT "Human UDP-glucuronosyltransferase, UGT1A8, glucuronidates
RT dihydrotestosterone to a monoglucuronide and further to a structurally
RT novel diglucuronide.";
RL Drug Metab. Dispos. 34:1102-1108(2006).
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).
RN [5]
RP INVOLVEMENT IN BONE MINERAL DENSITY VARIANCE.
RX PubMed=18992858; DOI=10.1016/j.ajhg.2008.10.006;
RA Yang T.-L., Chen X.-D., Guo Y., Lei S.-F., Wang J.-T., Zhou Q., Pan F.,
RA Chen Y., Zhang Z.-X., Dong S.-S., Xu X.-H., Yan H., Liu X., Qiu C.,
RA Zhu X.-Z., Chen T., Li M., Zhang H., Zhang L., Drees B.M., Hamilton J.J.,
RA Papasian C.J., Recker R.R., Song X.-P., Cheng J., Deng H.-W.;
RT "Genome-wide copy-number-variation study identified a susceptibility gene,
RT UGT2B17, for osteoporosis.";
RL Am. J. Hum. Genet. 83:663-674(2008).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19022937; DOI=10.1124/dmd.108.024844;
RA Sten T., Bichlmaier I., Kuuranne T., Leinonen A., Yli-Kauhaluoma J.,
RA Finel M.;
RT "UDP-glucuronosyltransferases (UGTs) 2B7 and UGT2B17 display converse
RT specificity in testosterone and epitestosterone glucuronidation, whereas
RT UGT2A1 conjugates both androgens similarly.";
RL Drug Metab. Dispos. 37:417-423(2009).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
RX PubMed=23288867; DOI=10.1124/dmd.112.049072;
RA Sneitz N., Vahermo M., Mosorin J., Laakkonen L., Poirier D., Finel M.;
RT "Regiospecificity and stereospecificity of human UDP-
RT glucuronosyltransferases in the glucuronidation of estriol, 16-epiestriol,
RT 17-epiestriol, and 13-epiestradiol.";
RL Drug Metab. Dispos. 41:582-591(2013).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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:8798464, PubMed:16595710, PubMed:18719240,
CC PubMed:19022937, PubMed:23288867). Catalyzes the glucuronidation of
CC endogenous steroid hormones such as androgens (epitestosterone,
CC androsterone) and estrogens (estradiol, epiestradiol) (PubMed:8798464,
CC PubMed:16595710, PubMed:18719240, PubMed:19022937, PubMed:23288867).
CC {ECO:0000269|PubMed:16595710, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:8798464}.
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:16595710, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:23288867,
CC ECO:0000269|PubMed:8798464};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:16595710, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:19022937, ECO:0000305|PubMed:23288867,
CC ECO:0000305|PubMed:8798464};
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:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000305|PubMed:23288867};
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:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52873;
CC Evidence={ECO:0000305|PubMed:23288867};
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, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52465;
CC Evidence={ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:23288867};
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:0000269|PubMed:16595710};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53001;
CC Evidence={ECO:0000305|PubMed:16595710};
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:0000269|PubMed:19022937};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52457;
CC Evidence={ECO:0000305|PubMed:19022937};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11.4 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=10 uM for testosterone (when assaying glucuronidation at position
CC 17) {ECO:0000269|PubMed:19022937};
CC KM=3.4 uM for testosterone {ECO:0000269|PubMed:8798464};
CC KM=0.7 uM for dihydrotestosterone {ECO:0000269|PubMed:8798464};
CC KM=1 uM for androstane-3alpha,17beta-diol
CC {ECO:0000269|PubMed:8798464};
CC Vmax=327 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=3.8 pmol/min/mg enzyme for the formation of 16alpha,17beta-
CC estriol 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=5.4 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 16-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=5.9 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=38.2 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=59.8 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=32.7 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=1626 pmol/min/mg enzyme for the formation of 5alpha-
CC dihydrotestosterone 17-O-(beta-D-glucuronate)
CC {ECO:0000269|PubMed:16595710};
CC Vmax=1002 pmol/min/mg enzyme for the formation of testosterone 17-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:19022937};
CC Vmax=50 pmol/min/mg enzyme for the formation of testosterone
CC {ECO:0000269|PubMed:8798464};
CC Vmax=51.7 pmol/min/mg enzyme for the formation of dihydrotestosterone
CC {ECO:0000269|PubMed:8798464};
CC Vmax=36.7 pmol/min/mg enzyme for the formation of androstane-
CC 3alpha,17beta-diol glucuronide {ECO:0000269|PubMed:8798464};
CC Note=Some kinetic parameters were assessed using commercial enzymes,
CC which may represent a mix of both active and inactive protein forms,
CC and therefore modify the kinetic values.
CC {ECO:0000305|PubMed:16595710};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:23288867}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in various tissues including the liver,
CC kidney, testis, uterus, placenta, mammary gland, adrenal gland, skin
CC and prostate. {ECO:0000269|PubMed:8798464}.
CC -!- POLYMORPHISM: Copy-number variation of UGT2B17 defines the bone mineral
CC density quantitative trait locus 12 (BMND12) [MIM:612560]. Variance in
CC bone mineral density is a susceptibility factor for osteoporotic
CC fractures. {ECO:0000269|PubMed:18992858}.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; U59209; AAC25491.1; -; mRNA.
DR CCDS; CCDS3523.1; -.
DR RefSeq; NP_001068.1; NM_001077.3.
DR AlphaFoldDB; O75795; -.
DR SMR; O75795; -.
DR BioGRID; 113214; 2.
DR STRING; 9606.ENSP00000320401; -.
DR BindingDB; O75795; -.
DR ChEMBL; CHEMBL4978; -.
DR DrugBank; DB12597; Asciminib.
DR DrugBank; DB15463; Belzutifan.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB01241; Gemfibrozil.
DR DrugBank; DB00678; Losartan.
DR DrugBank; DB00675; Tamoxifen.
DR SwissLipids; SLP:000001696; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyGen; O75795; 3 sites.
DR iPTMnet; O75795; -.
DR PhosphoSitePlus; O75795; -.
DR BioMuta; UGT2B17; -.
DR jPOST; O75795; -.
DR MassIVE; O75795; -.
DR MaxQB; O75795; -.
DR PaxDb; O75795; -.
DR PeptideAtlas; O75795; -.
DR PRIDE; O75795; -.
DR ProteomicsDB; 50199; -.
DR Antibodypedia; 44192; 30 antibodies from 18 providers.
DR DNASU; 7367; -.
DR Ensembl; ENST00000317746.3; ENSP00000320401.2; ENSG00000197888.3.
DR GeneID; 7367; -.
DR KEGG; hsa:7367; -.
DR MANE-Select; ENST00000317746.3; ENSP00000320401.2; NM_001077.4; NP_001068.1.
DR UCSC; uc021xov.2; human.
DR CTD; 7367; -.
DR DisGeNET; 7367; -.
DR GeneCards; UGT2B17; -.
DR HGNC; HGNC:12547; UGT2B17.
DR HPA; ENSG00000197888; Group enriched (intestine, liver).
DR MalaCards; UGT2B17; -.
DR MIM; 601903; gene.
DR MIM; 612560; phenotype.
DR neXtProt; NX_O75795; -.
DR OpenTargets; ENSG00000197888; -.
DR PharmGKB; PA37189; -.
DR VEuPathDB; HostDB:ENSG00000197888; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000163930; -.
DR HOGENOM; CLU_012949_3_2_1; -.
DR InParanoid; O75795; -.
DR OMA; YNIKLCE; -.
DR OrthoDB; 508327at2759; -.
DR PhylomeDB; O75795; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; O75795; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SABIO-RK; O75795; -.
DR SignaLink; O75795; -.
DR BioGRID-ORCS; 7367; 12 hits in 1001 CRISPR screens.
DR GeneWiki; UGT2B17; -.
DR GenomeRNAi; 7367; -.
DR Pharos; O75795; Tbio.
DR PRO; PR:O75795; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O75795; protein.
DR Bgee; ENSG00000197888; Expressed in mucosa of transverse colon and 105 other tissues.
DR Genevisible; O75795; HS.
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:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; TAS:ProtInc.
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; Glycoprotein; Glycosyltransferase; Lipid metabolism;
KW Membrane; Reference proteome; Signal; Steroid metabolism; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..530
FT /note="UDP-glucuronosyltransferase 2B17"
FT /id="PRO_0000036041"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 136
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWQ1"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 530 AA; 61095 MW; 8E59EBC43CF43760 CRC64;
MSLKWMSVFL LMQLSCYFSS GSCGKVLVWP TEYSHWINMK TILEELVQRG HEVIVLTSSA
SILVNASKSS AIKLEVYPTS LTKNDLEDFF MKMFDRWTYS ISKNTFWSYF SQLQELCWEY
SDYNIKLCED AVLNKKLMRK LQESKFDVLL ADAVNPCGEL LAELLNIPFL YSLRFSVGYT
VEKNGGGFLF PPSYVPVVMS ELSDQMIFME RIKNMIYMLY FDFWFQAYDL KKWDQFYSEV
LGRPTTLFET MGKAEMWLIR TYWDFEFPRP FLPNVDFVGG LHCKPAKPLP KEMEEFVQSS
GENGIVVFSL GSMISNMSEE SANMIASALA QIPQKVLWRF DGKKPNTLGS NTRLYKWLPQ
NDLLGHPKTK AFITHGGTNG IYEAIYHGIP MVGIPLFADQ HDNIAHMKAK GAALSVDIRT
MSSRDLLNAL KSVINDPIYK ENIMKLSRIH HDQPVKPLDR AVFWIEFVMR HKGAKHLRVA
AHNLTWIQYH SLDVIAFLLA CVATMIFMIT KCCLFCFRKL AKTGKKKKRD
