UD2A1_HUMAN
ID UD2A1_HUMAN Reviewed; 527 AA.
AC P0DTE4; B4E2F4; D3GER1; D3GER2; E9PDM7; J3KNA3; Q9Y4X1;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=UDP-glucuronosyltransferase 2A1 {ECO:0000303|PubMed:18719240};
DE Short=UDPGT 2A1;
DE Short=UGT2A1;
DE EC=2.4.1.17 {ECO:0000269|PubMed:10359671, ECO:0000269|PubMed:18719240, ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:19858781, ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:23756265};
DE Flags: Precursor;
GN Name=UGT2A1 {ECO:0000312|HGNC:HGNC:12542};
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] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Olfactory bulb;
RX PubMed=10359671; DOI=10.1042/bj3400837;
RA Jedlitschky G.A., Cassidy A.J., Sales M., Pratt N., Burchell B.;
RT "Cloning and characterization of a novel human olfactory UDP-
RT glucuronosyltransferase.";
RL Biochem. J. 340:837-843(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ILE-391.
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE
RP SPECIFICITY.
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 FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Nasal mucosa;
RX PubMed=19858781; DOI=10.1097/fpc.0b013e3283330767;
RA Sneitz N., Court M.H., Zhang X., Laajanen K., Yee K.K., Dalton P., Ding X.,
RA Finel M.;
RT "Human UDP-glucuronosyltransferase UGT2A2: cDNA construction, expression,
RT and functional characterization in comparison with UGT2A1 and UGT2A3.";
RL Pharmacogenet. Genomics 19:923-934(2009).
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, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23756265; DOI=10.1124/dmd.113.052613;
RA Perreault M., Gauthier-Landry L., Trottier J., Verreault M., Caron P.,
RA Finel M., Barbier O.;
RT "The Human UDP-glucuronosyltransferase UGT2A1 and UGT2A2 enzymes are highly
RT active in bile acid glucuronidation.";
RL Drug Metab. Dispos. 41:1616-1620(2013).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [9]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=26220143; DOI=10.1016/j.jsbmb.2015.07.013;
RA Kallionpaeae R.A., Jaervinen E., Finel M.;
RT "Glucuronidation of estrone and 16alpha-hydroxyestrone by human UGT
RT enzymes: The key roles of UGT1A10 and UGT2B7.";
RL J. Steroid Biochem. Mol. Biol. 154:104-111(2015).
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:10359671, PubMed:19858781, PubMed:18719240,
CC PubMed:19022937, PubMed:23756265, PubMed:23288867). Essential for the
CC elimination and detoxification of drugs, xenobiotics and endogenous
CC compounds (PubMed:10359671, PubMed:19858781, PubMed:23756265).
CC Catalyzes the glucuronidation of endogenous steroid hormones such as
CC androgens (testosterone and epitestosterone) and estrogens (estradiol
CC and epiestriol) (PubMed:18719240, PubMed:19858781, PubMed:19022937,
CC PubMed:23288867). Contributes to bile acid (BA) detoxification by
CC catalyzing the glucuronidation of BA substrates, which are natural
CC detergents for dietary lipids absorption (PubMed:23756265). Shows a
CC high affinity to aliphatic odorants such as citronellol as well as
CC olfactory tissue specificity, and therefore may be involved in
CC olfaction (PubMed:10359671). Shows a potential role in detoxification
CC of toxic waste compounds in the amniotic fluid before birth, and air-
CC born chemical after birth (PubMed:19858781).
CC {ECO:0000269|PubMed:10359671, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:19858781,
CC ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:23756265}.
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:10359671, ECO:0000269|PubMed:18719240,
CC ECO:0000269|PubMed:19022937, ECO:0000269|PubMed:19858781,
CC ECO:0000269|PubMed:23288867, ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:10359671, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:19022937, ECO:0000305|PubMed:19858781,
CC ECO:0000305|PubMed:23288867, ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16beta,17beta-estriol + UDP-alpha-D-glucuronate =
CC 16beta,17beta-estriol 16-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52880, ChEBI:CHEBI:15378, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:87620, ChEBI:CHEBI:136886;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52881;
CC Evidence={ECO:0000305|PubMed:23288867};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16alpha,17alpha-estriol + UDP-alpha-D-glucuronate =
CC 16alpha,17alpha-estriol 16-O-(beta-D-glucuronate) + H(+) + UDP;
CC Xref=Rhea:RHEA:52920, ChEBI:CHEBI:15378, ChEBI:CHEBI:42156,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136884;
CC Evidence={ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52921;
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:18719240, ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52873;
CC Evidence={ECO:0000305|PubMed:18719240, ECO:0000305|PubMed:23288867};
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:18719240, ECO:0000269|PubMed:19858781,
CC ECO:0000269|PubMed:23288867};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52869;
CC Evidence={ECO:0000269|PubMed:23288867, ECO:0000305|PubMed:18719240,
CC ECO:0000305|PubMed:19858781};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol
CC 3-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52460,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16469, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136641;
CC Evidence={ECO:0000269|PubMed:18719240};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52461;
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=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 -!- CATALYTIC ACTIVITY:
CC Reaction=epitestosterone + UDP-alpha-D-glucuronate = epitestosterone
CC 17-O-(beta-D-glucuronate) + H(+) + UDP; Xref=Rhea:RHEA:52568,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:42534, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136673;
CC Evidence={ECO:0000269|PubMed:19022937};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52569;
CC Evidence={ECO:0000305|PubMed:19022937};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + UDP-alpha-D-glucuronate = H(+) + lithocholoyl-
CC 3-O-(beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:53028,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29744, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:136965;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53029;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lithocholate + UDP-alpha-D-glucuronate = lithocholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52952, ChEBI:CHEBI:29744,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136902;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52953;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxycholate + UDP-alpha-D-glucuronate = deoxycholoyl-24-O-
CC (beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52948, ChEBI:CHEBI:23614,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:136901;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52949;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyodeoxycholate + UDP-alpha-D-glucuronate = hyodeoxycholoyl-
CC 24-O-(beta-D-glucuronate) + UDP; Xref=Rhea:RHEA:52956,
CC ChEBI:CHEBI:58052, ChEBI:CHEBI:58223, ChEBI:CHEBI:58875,
CC ChEBI:CHEBI:136903; Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52957;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hyocholate + UDP-alpha-D-glucuronate = hyocholoyl-24-O-(beta-
CC D-glucuronate) + UDP; Xref=Rhea:RHEA:52960, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:133661, ChEBI:CHEBI:136904;
CC Evidence={ECO:0000269|PubMed:23756265};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52961;
CC Evidence={ECO:0000305|PubMed:23756265};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=99 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=174 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 3) {ECO:0000269|PubMed:18719240};
CC KM=36 uM for 17alpha-estradiol/epiestradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=73 uM for 17beta-estradiol/estradiol (when assaying
CC glucuronidation at position 17) {ECO:0000269|PubMed:18719240};
CC KM=57 uM for estrone (when assaying glucuronidation at position 3)
CC {ECO:0000269|PubMed:26220143};
CC KM=160 uM for 16alpha-hydroxyestrone (when assaying glucuronidation
CC at position 16) {ECO:0000269|PubMed:26220143};
CC KM=38.7 uM for testosterone (when assaying glucuronidation at
CC position 17) {ECO:0000269|PubMed:19022937};
CC KM=11.6 uM for epitestosterone (when assaying glucuronidation at
CC position 17) {ECO:0000269|PubMed:19022937};
CC KM=251 uM for UDP-glucuronate (with 3-hydroxybiphenyl as substrate)
CC {ECO:0000269|PubMed:10359671};
CC KM=274 uM for UDP-glucuronate (with S-(-)-b-citronellol as substrate)
CC {ECO:0000269|PubMed:10359671};
CC KM=56.2 uM for testosterone {ECO:0000269|PubMed:10359671};
CC KM=75.4 uM for 3-hydroxybiphenyl {ECO:0000269|PubMed:10359671};
CC KM=59.5 uM for umbelliferone {ECO:0000269|PubMed:10359671};
CC KM=51.6 uM for S-(-)-b-citronellol {ECO:0000269|PubMed:10359671};
CC KM=170.1 uM for borneol {ECO:0000269|PubMed:10359671};
CC KM=39.5 uM for UDP-glucuronate (with 4-methyl-umbelliferone as
CC substrate) {ECO:0000269|PubMed:19858781};
CC KM=303 uM for 4-nitrophenol {ECO:0000269|PubMed:19858781};
CC KM=32.3 uM for 4-methyl-umbelliferone {ECO:0000269|PubMed:19858781};
CC KM=0.6 uM for 4-phenylphenol {ECO:0000269|PubMed:19858781};
CC KM=619 uM for 4-phenylphenol {ECO:0000269|PubMed:19858781};
CC KM=2344 uM for cholate (when assaying glucuronidation at position 24)
CC {ECO:0000269|PubMed:23756265};
CC KM=1744 uM for chenodeoxycholate (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:23756265};
CC KM=1397 uM for chenodeoxycholate (when assaying glucuronidation at
CC position 24) {ECO:0000269|PubMed:23756265};
CC KM=102.2 uM for lithocholate (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:23756265};
CC KM=102.3 uM for lithocholate (when assaying glucuronidation at
CC position 24) {ECO:0000269|PubMed:23756265};
CC KM=2405.6 uM for deoxycholate (when assaying glucuronidation at
CC position 3) {ECO:0000269|PubMed:23756265};
CC KM=917.9 uM for deoxycholate (when assaying glucuronidation at
CC position 24) {ECO:0000269|PubMed:23756265};
CC KM=237.4 uM for hyodeoxycholate (when assaying glucuronidation at
CC position 6) {ECO:0000269|PubMed:23756265};
CC KM=178.5 uM for hyodeoxycholate (when assaying glucuronidation at
CC position 24) {ECO:0000269|PubMed:23756265};
CC KM=210.7 uM for hyocholate (when assaying glucuronidation at position
CC 24) {ECO:0000269|PubMed:23756265};
CC Vmax=693 pmol/min/mg enzyme for the formation of 17alpha-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=128 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=78.3 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=265 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:18719240};
CC Vmax=57.1 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=4.6 pmol/min/mg enzyme for the formation of 17beta-estradiol 3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=485 pmol/min/mg enzyme for the formation of 17alpha-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=16.4 pmol/min/mg enzyme for the formation of 17beta-estradiol
CC 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=263 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 16-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=174 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 16-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=15.8 pmol/min/mg enzyme for the formation of 16alpha,17beta-
CC estriol 16-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=1.5 pmol/min/mg enzyme for the formation of 16beta,17beta-
CC estriol 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=3.9 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 3-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=5.9 pmol/min/mg enzyme for the formation of 16alpha,17alpha-
CC estriol 17-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23288867};
CC Vmax=51 pmol/min/mg enzyme for the formation of estrone 3-O-(beta-D-
CC glucuronate) {ECO:0000269|PubMed:26220143};
CC Vmax=210 pmol/min/mg enzyme for the formation of 16alpha-
CC hydroxyestrone 16-O-(beta-D-glucuronate)
CC {ECO:0000269|PubMed:26220143};
CC Vmax=427 pmol/min/mg enzyme for the formation of testosterone 17-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:19022937};
CC Vmax=271 pmol/min/mg enzyme for the formation of epitestosterone 17-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:19022937};
CC Vmax=250 pmol/min/mg enzyme with testosterone as substrate
CC {ECO:0000269|PubMed:10359671};
CC Vmax=2600 pmol/min/mg enzyme with 3-hydroxybiphenyl as substrate
CC {ECO:0000269|PubMed:10359671};
CC Vmax=610 pmol/min/mg enzyme with umbelliferone as substrate
CC {ECO:0000269|PubMed:10359671};
CC Vmax=1980 pmol/min/mg enzyme with S-(-)-b-citronellol as substrate
CC {ECO:0000269|PubMed:10359671};
CC Vmax=1050 pmol/min/mg enzyme with borneol as substrate
CC {ECO:0000269|PubMed:10359671};
CC Vmax=141 pmol/min/mg enzyme with 4-nitrophenol as substrate
CC {ECO:0000269|PubMed:19858781};
CC Vmax=537 pmol/min/mg enzyme with 4-methyl-umbelliferone as substrate
CC {ECO:0000269|PubMed:19858781};
CC Vmax=116 pmol/min/mg enzyme with 4-phenylphenol as substrate
CC {ECO:0000269|PubMed:19858781};
CC Vmax=325 pmol/min/mg enzyme with 4-phenylphenol as substrate
CC {ECO:0000269|PubMed:19858781};
CC Vmax=83.3 pmol/min/mg enzyme for the formation of choloyl-24-O-(beta-
CC D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=95 pmol/min/mg enzyme for the formation of chenodeoxycholoyl-3-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=536.7 pmol/min/mg enzyme for the formation of chenodeoxycholoyl-
CC 24-O-(beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=685 pmol/min/mg enzyme for the formation of lithocholoyl-3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=305.2 pmol/min/mg enzyme for the formation of lithocholoyl24-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=83.3 pmol/min/mg enzyme for the formation of deoxycholoyl-3-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=235.2 pmol/min/mg enzyme for the formation of deoxycholoyl-24-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=45.1 pmol/min/mg enzyme for the formation of hyodeoxycholate 6-
CC O-(beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=805.1 pmol/min/mg enzyme for the formation of hyocholoyl-24-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC Vmax=495.1 pmol/min/mg enzyme for the formation of hyocholoyl-24-O-
CC (beta-D-glucuronate) {ECO:0000269|PubMed:23756265};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:10359671}; Single-
CC pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000305|PubMed:19858781}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=P0DTE4-5, Q9Y4X1-5;
CC Sequence=Displayed;
CC Name=1;
CC IsoId=P0DTE4-1, Q9Y4X1-1;
CC Sequence=VSP_061419, VSP_061420;
CC Name=2;
CC IsoId=P0DTE4-4, Q9Y4X1-4;
CC Sequence=VSP_061418;
CC -!- TISSUE SPECIFICITY: Olfactory epithelium, brain and fetal lung
CC (PubMed:10359671). Not present in liver (PubMed:10359671).
CC {ECO:0000269|PubMed:10359671}.
CC -!- MISCELLANEOUS: UGT2A1 isoform is part of the UGT2A complex locus which
CC displays alternative use of promoters and exons. The locus is defined
CC by 2 alternative promoters giving rise to 2 fonctionally active
CC polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results
CC in additional isoforms for each protein class.
CC {ECO:0000303|PubMed:19858781}.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AJ006054; CAB41974.1; -; mRNA.
DR EMBL; AK304249; BAG65116.1; -; mRNA.
DR EMBL; AK314209; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC093829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS3529.1; -. [P0DTE4-1]
DR CCDS; CCDS58901.1; -.
DR CCDS; CCDS58902.1; -. [P0DTE4-4]
DR RefSeq; NP_001239203.2; NM_001252274.2.
DR RefSeq; NP_001239204.2; NM_001252275.2.
DR RefSeq; NP_001288168.1; NM_001301239.1.
DR RefSeq; NP_006789.3; NM_006798.4.
DR AlphaFoldDB; P0DTE4; -.
DR ChEMBL; CHEMBL1743321; -.
DR SwissLipids; SLP:000001983; -.
DR GlyGen; P0DTE4; 3 sites.
DR iPTMnet; Q9Y4X1; -.
DR PhosphoSitePlus; P0DTE4; -.
DR MassIVE; P0DTE4; -.
DR PeptideAtlas; P0DTE4; -.
DR Antibodypedia; 49675; 13 antibodies from 8 providers.
DR Antibodypedia; 72053; 7 antibodies from 4 providers.
DR DNASU; 10941; -.
DR Ensembl; ENST00000286604.9; ENSP00000286604.4; ENSG00000173610.13. [P0DTE4-5]
DR Ensembl; ENST00000503640.5; ENSP00000424478.1; ENSG00000173610.13. [P0DTE4-1]
DR Ensembl; ENST00000514019.1; ENSP00000425497.1; ENSG00000173610.13. [P0DTE4-4]
DR GeneID; 10941; -.
DR KEGG; hsa:10941; -.
DR MANE-Select; ENST00000286604.9; ENSP00000286604.4; NM_001252275.3; NP_001239204.2.
DR CTD; 10941; -.
DR GeneCards; UGT2A1; -.
DR HGNC; HGNC:12542; UGT2A1.
DR HPA; ENSG00000173610; Group enriched (choroid plexus, kidney, liver, pituitary gland).
DR HPA; ENSG00000271271; Group enriched (kidney, liver).
DR MIM; 604716; gene.
DR neXtProt; NX_P0DTE4; -.
DR OpenTargets; ENSG00000173610; -.
DR GeneTree; ENSGT00940000161344; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SignaLink; P0DTE4; -.
DR PRO; PR:P0DTE4; -.
DR Proteomes; UP000005640; Chromosome 4.
DR Bgee; ENSG00000173610; Expressed in olfactory segment of nasal mucosa and 43 other tissues.
DR ExpressionAtlas; P0DTE4; baseline and differential.
DR Genevisible; Q9Y4X1; 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:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008206; P:bile acid metabolic process; IDA:UniProtKB.
DR GO; GO:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007606; P:sensory perception of chemical stimulus; IDA:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; IEA:UniProtKB-KW.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR002213; UDP_glucos_trans.
DR InterPro; IPR035595; UDP_glycos_trans_CS.
DR Pfam; PF00201; UDPGT; 2.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lipid metabolism; Membrane; Olfaction;
KW Reference proteome; Sensory transduction; Signal; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..527
FT /note="UDP-glucuronosyltransferase 2A1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036023"
FT TOPO_DOM 21..491
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 492..512
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 513..527
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 239..282
FT /note="GGLLLCCPGWSAVADLGSLQPLLPGFKRFSRLSLHCSWDYRLPA -> DGSH
FT WLNIKIILEELIQRNHNVTVLASSATLFINSNPDSPVNFEVIPVSYKKSNIDSLIEHMI
FT MLWIDHRPTPLTIWAFYKELGKLLDTFFQINIQLCDGVLKNPKLMARLQKGGFDVLVAD
FT PVTICGDLVALKLGIPFMYTLRFSPASTVERHCGKIPAPVSYVPAALSELTDQMTFGER
FT IKNTISYSLQDYIFQSYWGEWNSYYSKIL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_061418"
FT VAR_SEQ 240..283
FT /note="Missing (in isoform 1)"
FT /id="VSP_061419"
FT VAR_SEQ 332
FT /note="K -> KEMEEFIQSSGKNGVVVFSLGSMVKNLTEEKANLIASALAQIPQK
FT (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10359671"
FT /id="VSP_061420"
FT VARIANT 391
FT /note="V -> I (in dbSNP:rs4148304)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_057326"
FT CONFLICT 92
FT /note="L -> S (in Ref. 1; CAB41974)"
FT /evidence="ECO:0000305"
FT CARBOHYD P0DTE4-1:313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT P0DTE4-1:308
FT /note="G -> R (in dbSNP:rs4148301)"
FT /id="VAR_024686"
SQ SEQUENCE 527 AA; 59963 MW; CFC20162D2AEBBB6 CRC64;
MLNNLLLFSL QISLIGTTLG GNVLIWPMEG SHWLNVKIII DELIKKEHNV TVLVASGALF
ITPTSNPSLT FEIYKVPFGK ERIEGVIKDF VLTWLENRPS PSTIWRFYQE MAKVIKDFHM
VSQEICDGVL KNQQLMAKLK KSKFEVLVSD PVFPCGDIVA LKLGIPFMYS LRFSPASTVE
KHCGKVPYPP SYVPAVLSEL TDQMSFTDRI RNFISYHLQD YMFETLWKSW DSYYSKALGG
LLLCCPGWSA VADLGSLQPL LPGFKRFSRL SLHCSWDYRL PAGRPTTLCE TMGKAEIWLI
RTYWDFEFPR PYLPNFEFVG GLHCKPAKPL PKVLWRYKGK KPATLGNNTQ LFDWIPQNDL
LGHPKTKAFI THGGTNGIYE AIYHGVPMVG VPMFADQPDN IAHMKAKGAA VEVNLNTMTS
VDLLSALRTV INEPSYKENA MRLSRIHHDQ PVKPLDRAVF WIEFVMRHKG AKHLRVAAHD
LTWFQYHSLD VIGFLLVCVT TAIFLVIQCC LFSCQKFGKI GKKKKRE
