Full text data of UGT2B28
UGT2B28
[Confidence: low (only semi-automatic identification from reviews)]
UDP-glucuronosyltransferase 2B28; UDPGT 2B28; 2.4.1.17; Flags: Precursor
UDP-glucuronosyltransferase 2B28; UDPGT 2B28; 2.4.1.17; Flags: Precursor
UniProt
Q9BY64
ID UDB28_HUMAN Reviewed; 529 AA.
AC Q9BY64; B5BUM0; Q9BY62; Q9BY63;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=UDP-glucuronosyltransferase 2B28;
DE Short=UDPGT 2B28;
DE EC=2.4.1.17;
DE Flags: Precursor;
GN Name=UGT2B28;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11300766; DOI=10.1021/bi002607y;
RA Levesque E., Turgeon D., Carrier J.-S., Montminy V., Beaulieu M.,
RA Belanger A.;
RT "Isolation and characterization of the UGT2B28 cDNA encoding a novel
RT human steroid conjugating UDP-glucuronosyltransferase.";
RL Biochemistry 40:3869-3881(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP HIS-365; ARG-447 AND ASP-458.
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
CC -!- FUNCTION: UDPGTs are of major importance in the conjugation and
CC subsequent elimination of potentially toxic xenobiotics and
CC endogenous compounds. This isozyme has glucuronidating capacity
CC with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-
CC diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems
CC to be active.
CC -!- CATALYTIC ACTIVITY: UDP-glucuronate + acceptor = UDP + acceptor
CC beta-D-glucuronoside.
CC -!- SUBCELLULAR LOCATION: Microsome membrane; Single-pass membrane
CC protein. Endoplasmic reticulum membrane; Single-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=I;
CC IsoId=Q9BY64-1; Sequence=Displayed;
CC Name=2; Synonyms=II;
CC IsoId=Q9BY64-2; Sequence=VSP_006710, VSP_006711;
CC -!- TISSUE SPECIFICITY: Expressed in the liver, breast and kidney.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK31809.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF177272; AAK31807.1; -; mRNA.
DR EMBL; AF177273; AAK31808.1; -; mRNA.
DR EMBL; AF177274; AAK31809.1; ALT_SEQ; mRNA.
DR EMBL; AB451456; BAG70270.1; -; mRNA.
DR RefSeq; NP_001193933.1; NM_001207004.1.
DR RefSeq; NP_444267.1; NM_053039.1.
DR RefSeq; XP_005265754.1; XM_005265697.1.
DR UniGene; Hs.653154; -.
DR ProteinModelPortal; Q9BY64; -.
DR SMR; Q9BY64; 285-446.
DR STRING; 9606.ENSP00000334276; -.
DR ChEMBL; CHEMBL6189; -.
DR DrugBank; DB01544; Flunitrazepam.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR PhosphoSite; Q9BY64; -.
DR DMDM; 20140759; -.
DR PaxDb; Q9BY64; -.
DR PRIDE; Q9BY64; -.
DR Ensembl; ENST00000335568; ENSP00000334276; ENSG00000135226.
DR Ensembl; ENST00000511240; ENSP00000427399; ENSG00000135226.
DR GeneID; 54490; -.
DR KEGG; hsa:54490; -.
DR UCSC; uc003hej.3; human.
DR CTD; 54490; -.
DR GeneCards; GC04P070194; -.
DR H-InvDB; HIX0031374; -.
DR HGNC; HGNC:13479; UGT2B28.
DR HPA; HPA045108; -.
DR MIM; 606497; gene.
DR neXtProt; NX_Q9BY64; -.
DR PharmGKB; PA37779; -.
DR eggNOG; COG1819; -.
DR HOGENOM; HOG000220831; -.
DR HOVERGEN; HBG004033; -.
DR InParanoid; Q9BY64; -.
DR KO; K00699; -.
DR OMA; KRWSDIQ; -.
DR OrthoDB; EOG7GBFWS; -.
DR PhylomeDB; Q9BY64; -.
DR Reactome; REACT_111217; Metabolism.
DR GenomeRNAi; 54490; -.
DR NextBio; 56811; -.
DR PRO; PR:Q9BY64; -.
DR Bgee; Q9BY64; -.
DR CleanEx; HS_UGT2B28; -.
DR Genevestigator; Q9BY64; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
DR InterPro; IPR002213; UDP_glucos_trans.
DR PANTHER; PTHR11926; PTHR11926; 1.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Membrane; Microsome; Polymorphism;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 24 Potential.
FT CHAIN 25 529 UDP-glucuronosyltransferase 2B28.
FT /FTId=PRO_0000036046.
FT TRANSMEM 495 517 Helical; (Potential).
FT CARBOHYD 315 315 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 335 335 V -> I (in isoform 2).
FT /FTId=VSP_006710.
FT VAR_SEQ 336 529 Missing (in isoform 2).
FT /FTId=VSP_006711.
FT VARIANT 365 365 L -> H (in dbSNP:rs4235127).
FT /FTId=VAR_059847.
FT VARIANT 447 447 I -> R (in dbSNP:rs6843900).
FT /FTId=VAR_060661.
FT VARIANT 458 458 H -> D (in dbSNP:rs6828191).
FT /FTId=VAR_060662.
FT CONFLICT 173 173 C -> R (in Ref. 2; BAG70270).
SQ SEQUENCE 529 AA; 60906 MW; 8C75277E964690C1 CRC64;
MALKWTSVLL LIHLGCYFSS GSCGKVLVWT GEYSHWMNMK TILKELVQRG HEVTVLASSA
SILFDPNDAF TLKLEVYPTS LTKTEFENII MQQVKRWSDI QKDSFWLYFS QEQEILWEFH
DIFRNFCKDV VSNKKVMKKL QESRFDIIFA DAFFPCGELL AALLNIPFVY SLCFTPGYTI
ERHSGGLIFP PSYIPVVMSK LSDQMTFMER VKNMIYVLYF DFWFQMCDMK KWDQFYSEVL
GRPTTLFETM GKADIWLMRN SWSFQFPHPF LPNIDFVGGL HCKPAKPLPK EMEEFVQSSG
ENGVVVFSLG SVISNMTAER ANVIATALAK IPQKVLWRFD GNKPDALGLN TRLYKWIPQN
DLLGLPKTRA FITHGGANGI YEAIYHGIPM VGIPLFWDQP DNIAHMKAKG AAVRLDFHTM
SSTDLLNALK TVINDPSYKE NVMKLSIIQH DQPVKPLHRA VFWIEFVMCH KGAKHLRVAA
RDLTWFQYHS LDVIGFLLAC VATVIFVVTK FCLFCFWKFA RKGKKGKRD
//
ID UDB28_HUMAN Reviewed; 529 AA.
AC Q9BY64; B5BUM0; Q9BY62; Q9BY63;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUN-2001, sequence version 1.
DT 22-JAN-2014, entry version 111.
DE RecName: Full=UDP-glucuronosyltransferase 2B28;
DE Short=UDPGT 2B28;
DE EC=2.4.1.17;
DE Flags: Precursor;
GN Name=UGT2B28;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC
RP ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11300766; DOI=10.1021/bi002607y;
RA Levesque E., Turgeon D., Carrier J.-S., Montminy V., Beaulieu M.,
RA Belanger A.;
RT "Isolation and characterization of the UGT2B28 cDNA encoding a novel
RT human steroid conjugating UDP-glucuronosyltransferase.";
RL Biochemistry 40:3869-3881(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP HIS-365; ARG-447 AND ASP-458.
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA Isogai T., Imai J., Watanabe S., Nomura N.;
RT "Human protein factory for converting the transcriptome into an in
RT vitro-expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
CC -!- FUNCTION: UDPGTs are of major importance in the conjugation and
CC subsequent elimination of potentially toxic xenobiotics and
CC endogenous compounds. This isozyme has glucuronidating capacity
CC with steroid substrates such as 5-beta-androstane 3-alpha,17-beta-
CC diol, estradiol, ADT, eugenol and bile acids. Only isoform 1 seems
CC to be active.
CC -!- CATALYTIC ACTIVITY: UDP-glucuronate + acceptor = UDP + acceptor
CC beta-D-glucuronoside.
CC -!- SUBCELLULAR LOCATION: Microsome membrane; Single-pass membrane
CC protein. Endoplasmic reticulum membrane; Single-pass membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=I;
CC IsoId=Q9BY64-1; Sequence=Displayed;
CC Name=2; Synonyms=II;
CC IsoId=Q9BY64-2; Sequence=VSP_006710, VSP_006711;
CC -!- TISSUE SPECIFICITY: Expressed in the liver, breast and kidney.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK31809.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF177272; AAK31807.1; -; mRNA.
DR EMBL; AF177273; AAK31808.1; -; mRNA.
DR EMBL; AF177274; AAK31809.1; ALT_SEQ; mRNA.
DR EMBL; AB451456; BAG70270.1; -; mRNA.
DR RefSeq; NP_001193933.1; NM_001207004.1.
DR RefSeq; NP_444267.1; NM_053039.1.
DR RefSeq; XP_005265754.1; XM_005265697.1.
DR UniGene; Hs.653154; -.
DR ProteinModelPortal; Q9BY64; -.
DR SMR; Q9BY64; 285-446.
DR STRING; 9606.ENSP00000334276; -.
DR ChEMBL; CHEMBL6189; -.
DR DrugBank; DB01544; Flunitrazepam.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR PhosphoSite; Q9BY64; -.
DR DMDM; 20140759; -.
DR PaxDb; Q9BY64; -.
DR PRIDE; Q9BY64; -.
DR Ensembl; ENST00000335568; ENSP00000334276; ENSG00000135226.
DR Ensembl; ENST00000511240; ENSP00000427399; ENSG00000135226.
DR GeneID; 54490; -.
DR KEGG; hsa:54490; -.
DR UCSC; uc003hej.3; human.
DR CTD; 54490; -.
DR GeneCards; GC04P070194; -.
DR H-InvDB; HIX0031374; -.
DR HGNC; HGNC:13479; UGT2B28.
DR HPA; HPA045108; -.
DR MIM; 606497; gene.
DR neXtProt; NX_Q9BY64; -.
DR PharmGKB; PA37779; -.
DR eggNOG; COG1819; -.
DR HOGENOM; HOG000220831; -.
DR HOVERGEN; HBG004033; -.
DR InParanoid; Q9BY64; -.
DR KO; K00699; -.
DR OMA; KRWSDIQ; -.
DR OrthoDB; EOG7GBFWS; -.
DR PhylomeDB; Q9BY64; -.
DR Reactome; REACT_111217; Metabolism.
DR GenomeRNAi; 54490; -.
DR NextBio; 56811; -.
DR PRO; PR:Q9BY64; -.
DR Bgee; Q9BY64; -.
DR CleanEx; HS_UGT2B28; -.
DR Genevestigator; Q9BY64; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
DR InterPro; IPR002213; UDP_glucos_trans.
DR PANTHER; PTHR11926; PTHR11926; 1.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Glycosyltransferase; Membrane; Microsome; Polymorphism;
KW Reference proteome; Signal; Transferase; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 24 Potential.
FT CHAIN 25 529 UDP-glucuronosyltransferase 2B28.
FT /FTId=PRO_0000036046.
FT TRANSMEM 495 517 Helical; (Potential).
FT CARBOHYD 315 315 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 335 335 V -> I (in isoform 2).
FT /FTId=VSP_006710.
FT VAR_SEQ 336 529 Missing (in isoform 2).
FT /FTId=VSP_006711.
FT VARIANT 365 365 L -> H (in dbSNP:rs4235127).
FT /FTId=VAR_059847.
FT VARIANT 447 447 I -> R (in dbSNP:rs6843900).
FT /FTId=VAR_060661.
FT VARIANT 458 458 H -> D (in dbSNP:rs6828191).
FT /FTId=VAR_060662.
FT CONFLICT 173 173 C -> R (in Ref. 2; BAG70270).
SQ SEQUENCE 529 AA; 60906 MW; 8C75277E964690C1 CRC64;
MALKWTSVLL LIHLGCYFSS GSCGKVLVWT GEYSHWMNMK TILKELVQRG HEVTVLASSA
SILFDPNDAF TLKLEVYPTS LTKTEFENII MQQVKRWSDI QKDSFWLYFS QEQEILWEFH
DIFRNFCKDV VSNKKVMKKL QESRFDIIFA DAFFPCGELL AALLNIPFVY SLCFTPGYTI
ERHSGGLIFP PSYIPVVMSK LSDQMTFMER VKNMIYVLYF DFWFQMCDMK KWDQFYSEVL
GRPTTLFETM GKADIWLMRN SWSFQFPHPF LPNIDFVGGL HCKPAKPLPK EMEEFVQSSG
ENGVVVFSLG SVISNMTAER ANVIATALAK IPQKVLWRFD GNKPDALGLN TRLYKWIPQN
DLLGLPKTRA FITHGGANGI YEAIYHGIPM VGIPLFWDQP DNIAHMKAKG AAVRLDFHTM
SSTDLLNALK TVINDPSYKE NVMKLSIIQH DQPVKPLHRA VFWIEFVMCH KGAKHLRVAA
RDLTWFQYHS LDVIGFLLAC VATVIFVVTK FCLFCFWKFA RKGKKGKRD
//
MIM
606497
*RECORD*
*FIELD* NO
606497
*FIELD* TI
*606497 URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASE 2 FAMILY, MEMBER B28; UGT2B28
*FIELD* TX
read moreFor background information on the UDP glycosyltransferase (UGT) gene
family, see UGT1A1 (191740). UGT2B glycosyltransferases catalyze the
transfer of glucuronic acid to a large number of endogenous compounds,
particularly steroids, to facilitate their elimination from target
cells.
CLONING
By screening a prostate carcinoma cDNA library with a pool of UGT2B4
(600067), UGT2B7 (600068), and UGT2B15 (600069) probes, followed by
RT-PCR analysis, Levesque et al. (2001) isolated cDNAs encoding 3
isoforms of UGT2B28, which they designated UGT2B28 types I, II, and III.
Sequence analysis predicted that the 529-amino acid type I protein,
which is 89% and 95% identical to UGTB10 (600070) and UGT2B11 (603064),
respectively, contains an endoplasmic reticulum (ER)-targeting signal, a
membrane-anchoring region, and substrate- and cofactor-binding domains.
The 335-amino acid type II isoform lacks the UDPGA-binding domain and
the transmembrane region. The 412-amino acid type III isoform retains
the transmembrane region at its C-terminal end but lacks the
substrate-binding domain. All 3 types possess only 1 N-linked
glycosylation site. Western blot analysis showed expression of 52-, 35-,
and 42-kD proteins, corresponding to the type I, II, and III UGT2B28
proteins, respectively. Northern blot analysis revealed UGT2B28 type I,
II, and III transcripts of 1.6, 1.4, and 1.3 kb, respectively, expressed
in a kidney cell line. RT-PCR analysis detected all 3 forms in liver and
mammary gland. Type III was also expressed in several other tissues and
breast cancer cell lines. Functional analysis indicated glucuronidating
capacity with steroid substrates for UGT2B28 type I, but not for the
type II or III forms. Immunofluorescence analysis demonstrated
expression of all 3 types in the perinuclear structure and in the ER,
where they colocalized with protein disulfide isomerase (P4HB; 176790).
GENE STRUCTURE
By screening a PAC genomic library, Levesque et al. (2001) determined
that the UGT2B28 gene contains at least 5 exons.
MAPPING
By screening a PAC genomic library, Levesque et al. (2001) determined
that the UGT2B28 gene maps to chromosome 4, where the other UGT2B genes
are clustered.
POPULATION GENETICS
Using DNA from 100 healthy unrelated Caucasian volunteers, Menard et al.
(2009) characterized the common UGT2B17 (601903) and UGT2B28 deletions
and observed that copy number variation (CNV) of UGT2B17 and UGT2B28
occur in Caucasians at 27% and 13.5%, respectively, with 43% carrying 2
copies of both genes and 57% harboring at least 1 deletion. CNVs of both
UGT2B17 and UGT2B28, with the cooccurrence of the D85Y polymorphism
(dbSNP rs1902023) in the UGT2B15 gene (600069), generate 7 distinct
haplotypes. The authors concluded that analyzing CNV of UGT2B17 without
evaluating UGT2B28 and the D85Y variant in UGT2B15 may over- or
underestimate the phenotypic impact of each gene.
*FIELD* RF
1. Levesque, E.; Turgeon, D.; Carrier, J.-S.; Montminy, V.; Beaulieu,
M.; Belanger, A.: Isolation and characterization of the UGT2B28 cDNA
encoding a novel human steroid conjugating UDP-glucuronosyltransferase. Biochemistry 40:
3869-3881, 2001.
2. Menard, V.; Eap, O.; Harvey, M.; Guillemette, C.; Levesque, E.
: Copy-number variations (CNVs) of the human sex steroid metabolizing
genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional
polymorphism. Hum. Mutat. 30: 1310-1319, 2009.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/17/2009
*FIELD* CD
Paul J. Converse: 11/26/2001
*FIELD* ED
wwang: 11/23/2009
terry: 11/17/2009
mgross: 11/26/2001
*RECORD*
*FIELD* NO
606497
*FIELD* TI
*606497 URIDINE DIPHOSPHATE GLYCOSYLTRANSFERASE 2 FAMILY, MEMBER B28; UGT2B28
*FIELD* TX
read moreFor background information on the UDP glycosyltransferase (UGT) gene
family, see UGT1A1 (191740). UGT2B glycosyltransferases catalyze the
transfer of glucuronic acid to a large number of endogenous compounds,
particularly steroids, to facilitate their elimination from target
cells.
CLONING
By screening a prostate carcinoma cDNA library with a pool of UGT2B4
(600067), UGT2B7 (600068), and UGT2B15 (600069) probes, followed by
RT-PCR analysis, Levesque et al. (2001) isolated cDNAs encoding 3
isoforms of UGT2B28, which they designated UGT2B28 types I, II, and III.
Sequence analysis predicted that the 529-amino acid type I protein,
which is 89% and 95% identical to UGTB10 (600070) and UGT2B11 (603064),
respectively, contains an endoplasmic reticulum (ER)-targeting signal, a
membrane-anchoring region, and substrate- and cofactor-binding domains.
The 335-amino acid type II isoform lacks the UDPGA-binding domain and
the transmembrane region. The 412-amino acid type III isoform retains
the transmembrane region at its C-terminal end but lacks the
substrate-binding domain. All 3 types possess only 1 N-linked
glycosylation site. Western blot analysis showed expression of 52-, 35-,
and 42-kD proteins, corresponding to the type I, II, and III UGT2B28
proteins, respectively. Northern blot analysis revealed UGT2B28 type I,
II, and III transcripts of 1.6, 1.4, and 1.3 kb, respectively, expressed
in a kidney cell line. RT-PCR analysis detected all 3 forms in liver and
mammary gland. Type III was also expressed in several other tissues and
breast cancer cell lines. Functional analysis indicated glucuronidating
capacity with steroid substrates for UGT2B28 type I, but not for the
type II or III forms. Immunofluorescence analysis demonstrated
expression of all 3 types in the perinuclear structure and in the ER,
where they colocalized with protein disulfide isomerase (P4HB; 176790).
GENE STRUCTURE
By screening a PAC genomic library, Levesque et al. (2001) determined
that the UGT2B28 gene contains at least 5 exons.
MAPPING
By screening a PAC genomic library, Levesque et al. (2001) determined
that the UGT2B28 gene maps to chromosome 4, where the other UGT2B genes
are clustered.
POPULATION GENETICS
Using DNA from 100 healthy unrelated Caucasian volunteers, Menard et al.
(2009) characterized the common UGT2B17 (601903) and UGT2B28 deletions
and observed that copy number variation (CNV) of UGT2B17 and UGT2B28
occur in Caucasians at 27% and 13.5%, respectively, with 43% carrying 2
copies of both genes and 57% harboring at least 1 deletion. CNVs of both
UGT2B17 and UGT2B28, with the cooccurrence of the D85Y polymorphism
(dbSNP rs1902023) in the UGT2B15 gene (600069), generate 7 distinct
haplotypes. The authors concluded that analyzing CNV of UGT2B17 without
evaluating UGT2B28 and the D85Y variant in UGT2B15 may over- or
underestimate the phenotypic impact of each gene.
*FIELD* RF
1. Levesque, E.; Turgeon, D.; Carrier, J.-S.; Montminy, V.; Beaulieu,
M.; Belanger, A.: Isolation and characterization of the UGT2B28 cDNA
encoding a novel human steroid conjugating UDP-glucuronosyltransferase. Biochemistry 40:
3869-3881, 2001.
2. Menard, V.; Eap, O.; Harvey, M.; Guillemette, C.; Levesque, E.
: Copy-number variations (CNVs) of the human sex steroid metabolizing
genes UGT2B17 and UGT2B28 and their associations with a UGT2B15 functional
polymorphism. Hum. Mutat. 30: 1310-1319, 2009.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/17/2009
*FIELD* CD
Paul J. Converse: 11/26/2001
*FIELD* ED
wwang: 11/23/2009
terry: 11/17/2009
mgross: 11/26/2001