ID   UD19_HUMAN              Reviewed;         530 AA.
AC   O60656; B8K285; P36509; Q9HAX0;
DT   11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   13-FEB-2019, entry version 165.
DE   RecName: Full=UDP-glucuronosyltransferase 1-9;
DE            Short=UDPGT 1-9;
DE            Short=UGT1*9;
DE            Short=UGT1-09;
DE            Short=UGT1.9;
DE            EC=2.4.1.17;
DE   AltName: Full=UDP-glucuronosyltransferase 1-I;
DE            Short=UGT-1I;
DE            Short=UGT1I;
DE   AltName: Full=UDP-glucuronosyltransferase 1A9;
DE   AltName: Full=lugP4;
DE   Flags: Precursor;
GN   Name=UGT1A9; Synonyms=GNT1, UGT1;
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].
RC   TISSUE=Liver;
RX   PubMed=1910331; DOI=10.1042/bj2780465;
RA   Wooster R., Sutherland L., Ebner T., Clarke D., da Cruz e Silva O.,
RA   Burchell B.;
RT   "Cloning and stable expression of a new member of the human liver
RT   phenol/bilirubin: UDP-glucuronosyltransferase cDNA family.";
RL   Biochem. J. 278:465-469(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Ciotti M., Potter C., Owens I.S.;
RT   "Human phenol metabolizing UDP-glucuronosyltransferase.";
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11434514; DOI=10.1097/00008571-200106000-00011;
RA   Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K.,
RA   Kubota S., Carvalho S., Pennington M.W., Owens I.S., Popescu N.C.;
RT   "Thirteen UDP-glucuronosyltransferase genes are encoded at the human
RT   UGT1 gene complex locus.";
RL   Pharmacogenetics 11:357-368(2001).
RN   [4]
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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-285.
RA   Owens I.S., Gong Q., Cho J.W., Potter C., Gholami N.;
RT   "Human phenol UDP-glucuronosyltransferase (UGT1A9) gene isozyme exon
RT   1.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RA   Guillemette C., Levesque E., Girard H., Bernard O.;
RL   Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=18004212; DOI=10.1097/FPC.0b013e3282f1f118;
RA   Girard H., Levesque E., Bellemare J., Journault K., Caillier B.,
RA   Guillemette C.;
RT   "Genetic diversity at the UGT1 locus is amplified by a novel 3'
RT   alternative splicing mechanism leading to nine additional UGT1A
RT   proteins that act as regulators of glucuronidation activity.";
RL   Pharmacogenet. Genomics 17:1077-1089(2007).
RN   [9]
RP   FUNCTION.
RX   PubMed=19545173; DOI=10.1021/mp8002557;
RA   Tang L., Singh R., Liu Z., Hu M.;
RT   "Structure and concentration changes affect characterization of UGT
RT   isoform-specific metabolism of isoflavones.";
RL   Mol. Pharm. 6:1466-1482(2009).
RN   [10]
RP   CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), AND SUBUNIT.
RX   PubMed=20610558; DOI=10.1124/dmd.110.034835;
RA   Bellemare J., Rouleau M., Girard H., Harvey M., Guillemette C.;
RT   "Alternatively spliced products of the UGT1A gene interact with the
RT   enzymatically active proteins to inhibit glucuronosyltransferase
RT   activity in vitro.";
RL   Drug Metab. Dispos. 38:1785-1789(2010).
RN   [11]
RP   GLYCOSYLATION AT ASN-71; ASN-292 AND ASN-344.
RX   PubMed=19951703; DOI=10.1016/j.bcp.2009.11.020;
RA   Nakajima M., Koga T., Sakai H., Yamanaka H., Fujiwara R., Yokoi T.;
RT   "N-Glycosylation plays a role in protein folding of human UGT1A9.";
RL   Biochem. Pharmacol. 79:1165-1172(2010).
RN   [12]
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [13]
RP   VARIANT [LARGE SCALE ANALYSIS] ILE-442.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
RN   [14]
RP   VARIANT THR-33.
RX   PubMed=19204906; DOI=10.1002/humu.20946;
RA   Menard V., Girard H., Harvey M., Perusse L., Guillemette C.;
RT   "Analysis of inherited genetic variations at the UGT1 locus in the
RT   French-Canadian population.";
RL   Hum. Mutat. 30:677-687(2009).
CC   -!- FUNCTION: UDPGT is of major importance in the conjugation and
CC       subsequent elimination of potentially toxic xenobiotics and
CC       endogenous compounds. This isoform has specificity for phenols.
CC       Isoform 2 lacks transferase activity but acts as a negative
CC       regulator of isoform 1. {ECO:0000269|PubMed:19545173}.
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:18004212,
CC         ECO:0000269|PubMed:20610558};
CC   -!- SUBUNIT: Isoform 1 interacts with isoform 2/i2 suggesting that
CC       oligomerization is involved in negative regulation of transferase
CC       activity by isoform 2. Isoform 1 also interacts with respective i2
CC       isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and
CC       UGT1A10. {ECO:0000269|PubMed:20610558}.
CC   -!- SUBCELLULAR LOCATION: Microsome. Endoplasmic reticulum membrane
CC       {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=i1;
CC         IsoId=O60656-1; Sequence=Displayed;
CC       Name=2; Synonyms=i2, UGT1A9s;
CC         IsoId=O60656-2; Sequence=VSP_053965;
CC   -!- TISSUE SPECIFICITY: Liver. Isoform 1 and isoform 2 are expressed
CC       in liver, kidney, colon, esophagus and small intestine.
CC       {ECO:0000269|PubMed:18004212}.
CC   -!- MISCELLANEOUS: The gene is part of the UGT1A complex locus which
CC       displays alternative use of promoters, first exons and terminal
CC       exons. The locus is defined by 13 first exons, which are
CC       alternatively spliced to 3 other common exons and 2 alternative
CC       terminal exons 5. From the 27 possible mRNA isoforms, 9 produce
CC       functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7,
CC       1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative
CC       exon 5 (5b) as terminal exon is leading to 9 additional
CC       alternatively spliced products termed isoforms i2 and which lack
CC       transferase activity.
CC   -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB19791.2; Type=Frameshift; Positions=59, 82; Evidence={ECO:0000305};
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DR   EMBL; S55985; AAB19791.2; ALT_FRAME; mRNA.
DR   EMBL; AF056188; AAC31425.1; -; mRNA.
DR   EMBL; AF297093; AAG30418.1; -; Genomic_DNA.
DR   EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC019072; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC058844; AAH58844.1; -; mRNA.
DR   EMBL; AF297091; AAG29816.1; -; Genomic_DNA.
DR   EMBL; DQ364246; ABC96770.1; -; mRNA.
DR   CCDS; CCDS2505.1; -. [O60656-1]
DR   PIR; S17512; S17512.
DR   RefSeq; NP_066307.1; NM_021027.2. [O60656-1]
DR   UniGene; Hs.554822; -.
DR   ProteinModelPortal; O60656; -.
DR   BioGrid; 120073; 7.
DR   IntAct; O60656; 7.
DR   STRING; 9606.ENSP00000346768; -.
DR   BindingDB; O60656; -.
DR   ChEMBL; CHEMBL1743319; -.
DR   DrugBank; DB00316; Acetaminophen.
DR   DrugBank; DB06403; Ambrisentan.
DR   DrugBank; DB00921; Buprenorphine.
DR   DrugBank; DB08907; Canagliflozin.
DR   DrugBank; DB06695; Dabigatran etexilate.
DR   DrugBank; DB06292; Dapagliflozin.
DR   DrugBank; DB00494; Entacapone.
DR   DrugBank; DB00749; Etodolac.
DR   DrugBank; DB04953; Ezogabine.
DR   DrugBank; DB00712; Flurbiprofen.
DR   DrugBank; DB06741; Gavestinel.
DR   DrugBank; DB00502; Haloperidol.
DR   DrugBank; DB00062; Human Serum Albumin.
DR   DrugBank; DB00327; Hydromorphone.
DR   DrugBank; DB01050; Ibuprofen.
DR   DrugBank; DB00328; Indomethacin.
DR   DrugBank; DB00762; Irinotecan.
DR   DrugBank; DB06738; Ketobemidone.
DR   DrugBank; DB01283; Lumiracoxib.
DR   DrugBank; DB00688; Mycophenolate mofetil.
DR   DrugBank; DB01024; Mycophenolic acid.
DR   DrugBank; DB00731; Nateglinide.
DR   DrugBank; DB04552; Niflumic Acid.
DR   DrugBank; DB00842; Oxazepam.
DR   DrugBank; DB04824; Phenolphthalein.
DR   DrugBank; DB00818; Propofol.
DR   DrugBank; DB08896; Regorafenib.
DR   DrugBank; DB00398; Sorafenib.
DR   DrugBank; DB01015; Sulfamethoxazole.
DR   DrugBank; DB06204; Tapentadol.
DR   DrugBank; DB00197; Troglitazone.
DR   DrugBank; DB00580; Valdecoxib.
DR   DrugBank; DB00313; Valproic Acid.
DR   DrugBank; DB00744; Zileuton.
DR   SwissLipids; SLP:000001713; -. [O60656-1]
DR   CAZy; GT1; Glycosyltransferase Family 1.
DR   GlyConnect; 1881; -.
DR   iPTMnet; O60656; -.
DR   PhosphoSitePlus; O60656; -.
DR   BioMuta; UGT1A9; -.
DR   jPOST; O60656; -.
DR   PaxDb; O60656; -.
DR   PeptideAtlas; O60656; -.
DR   PRIDE; O60656; -.
DR   ProteomicsDB; 49498; -.
DR   DNASU; 54600; -.
DR   Ensembl; ENST00000354728; ENSP00000346768; ENSG00000241119. [O60656-1]
DR   GeneID; 54600; -.
DR   KEGG; hsa:54600; -.
DR   CTD; 54600; -.
DR   DisGeNET; 54600; -.
DR   EuPathDB; HostDB:ENSG00000241119.1; -.
DR   GeneCards; UGT1A9; -.
DR   HGNC; HGNC:12541; UGT1A9.
DR   MIM; 191740; gene.
DR   MIM; 606434; gene.
DR   neXtProt; NX_O60656; -.
DR   OpenTargets; ENSG00000241119; -.
DR   PharmGKB; PA419; -.
DR   eggNOG; KOG1192; Eukaryota.
DR   eggNOG; COG1819; LUCA.
DR   GeneTree; ENSGT00940000163976; -.
DR   HOGENOM; HOG000220832; -.
DR   HOVERGEN; HBG004033; -.
DR   InParanoid; O60656; -.
DR   KO; K00699; -.
DR   OMA; LMGSYND; -.
DR   OrthoDB; 508327at2759; -.
DR   PhylomeDB; O60656; -.
DR   TreeFam; TF315472; -.
DR   BRENDA; 2.4.1.17; 2681.
DR   Reactome; R-HSA-156588; Glucuronidation.
DR   Reactome; R-HSA-1989781; PPARA activates gene expression.
DR   SABIO-RK; O60656; -.
DR   SIGNOR; O60656; -.
DR   GeneWiki; UGT1A9; -.
DR   GenomeRNAi; 54600; -.
DR   PRO; PR:O60656; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000241119; Expressed in 25 organ(s), highest expression level in adult mammalian kidney.
DR   Genevisible; O60656; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR   GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR   GO; GO:0004857; F:enzyme inhibitor activity; IGI:BHF-UCL.
DR   GO; GO:0015020; F:glucuronosyltransferase activity; IDA:UniProtKB.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0001972; F:retinoic acid binding; IDA:BHF-UCL.
DR   GO; GO:0008194; F:UDP-glycosyltransferase activity; IBA:GO_Central.
DR   GO; GO:0052695; P:cellular glucuronidation; IDA:UniProtKB.
DR   GO; GO:0051552; P:flavone metabolic process; IDA:BHF-UCL.
DR   GO; GO:0052696; P:flavonoid glucuronidation; IDA:BHF-UCL.
DR   GO; GO:2001030; P:negative regulation of cellular glucuronidation; IDA:UniProtKB.
DR   GO; GO:0045922; P:negative regulation of fatty acid metabolic process; IDA:BHF-UCL.
DR   GO; GO:1904224; P:negative regulation of glucuronosyltransferase activity; IDA:BHF-UCL.
DR   GO; GO:0019216; P:regulation of lipid metabolic process; TAS:Reactome.
DR   GO; GO:0042573; P:retinoic acid metabolic process; IC:BHF-UCL.
DR   GO; GO:0052697; P:xenobiotic glucuronidation; IDA:BHF-UCL.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
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   Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW   Glycoprotein; Glycosyltransferase; Membrane; Microsome; Polymorphism;
KW   Reference proteome; Signal; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     25       {ECO:0000255}.
FT   CHAIN        26    530       UDP-glucuronosyltransferase 1-9.
FT                                /FTId=PRO_0000036008.
FT   TRANSMEM    488    504       Helical. {ECO:0000255}.
FT   MOD_RES      99     99       N6-succinyllysine.
FT                                {ECO:0000250|UniProtKB:Q62452}.
FT   CARBOHYD     71     71       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:19951703}.
FT   CARBOHYD    292    292       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:19951703}.
FT   CARBOHYD    344    344       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:19951703}.
FT   VAR_SEQ     432    530       SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLR
FT                                PAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRK
FT                                CLGKKGRVKKAHKSKTH -> RKKQQSGRQM (in
FT                                isoform 2). {ECO:0000305}.
FT                                /FTId=VSP_053965.
FT   VARIANT      33     33       M -> T (in dbSNP:rs72551330).
FT                                {ECO:0000269|PubMed:19204906}.
FT                                /FTId=VAR_058587.
FT   VARIANT     442    442       S -> I (in a breast cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_036035.
FT   CONFLICT     29     29       L -> V (in Ref. 1; AAB19791).
FT                                {ECO:0000305}.
FT   CONFLICT    200    200       A -> D (in Ref. 1; AAB19791).
FT                                {ECO:0000305}.
FT   CONFLICT    279    282       QGKP -> ERKA (in Ref. 1; AAB19791).
FT                                {ECO:0000305}.
SQ   SEQUENCE   530 AA;  59941 MW;  C417B9E86B403078 CRC64;
     MACTGWTSPL PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MRSVVEKLIL RGHEVVVVMP
     EVSWQLGRSL NCTVKTYSTS YTLEDLDREF KAFAHAQWKA QVRSIYSLLM GSYNDIFDLF
     FSNCRSLFKD KKLVEYLKES SFDAVFLDPF DNCGLIVAKY FSLPSVVFAR GILCHYLEEG
     AQCPAPLSYV PRILLGFSDA MTFKERVRNH IMHLEEHLLC HRFFKNALEI ASEILQTPVT
     EYDLYSHTSI WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY INASGEHGIV
     VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK WLPQNDLLGH
     PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR METKGAGVTL NVLEMTSEDL
     ENALKAVIND KSYKENIMRL SSLHKDRPVE PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW
     YQYHSLDVIG FLLAVVLTVA FITFKCCAYG YRKCLGKKGR VKKAHKSKTH
//