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O60656

- UD19_HUMAN

UniProt

O60656 - UD19_HUMAN

Protein

UDP-glucuronosyltransferase 1-9

Gene

UGT1A9

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.1 Publication

    Catalytic activityi

    UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.2 Publications

    GO - Molecular functioni

    1. enzyme binding Source: BHF-UCL
    2. enzyme inhibitor activity Source: BHF-UCL
    3. glucuronosyltransferase activity Source: BHF-UCL
    4. protein heterodimerization activity Source: UniProt
    5. protein homodimerization activity Source: UniProt
    6. retinoic acid binding Source: BHF-UCL

    GO - Biological processi

    1. cellular glucuronidation Source: UniProt
    2. cellular lipid metabolic process Source: Reactome
    3. drug metabolic process Source: BHF-UCL
    4. flavone metabolic process Source: BHF-UCL
    5. flavonoid glucuronidation Source: BHF-UCL
    6. metabolic process Source: ProtInc
    7. negative regulation of catalytic activity Source: GOC
    8. negative regulation of cellular glucuronidation Source: UniProtKB
    9. negative regulation of fatty acid metabolic process Source: BHF-UCL
    10. retinoic acid metabolic process Source: BHF-UCL
    11. small molecule metabolic process Source: Reactome
    12. xenobiotic glucuronidation Source: BHF-UCL
    13. xenobiotic metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Glycosyltransferase, Transferase

    Enzyme and pathway databases

    BRENDAi2.4.1.17. 2681.
    ReactomeiREACT_116145. PPARA activates gene expression.
    REACT_6784. Glucuronidation.
    SABIO-RKO60656.

    Protein family/group databases

    CAZyiGT1. Glycosyltransferase Family 1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    UDP-glucuronosyltransferase 1-9 (EC:2.4.1.17)
    Short name:
    UDPGT 1-9
    Short name:
    UGT1*9
    Short name:
    UGT1-09
    Short name:
    UGT1.9
    Alternative name(s):
    UDP-glucuronosyltransferase 1-I
    Short name:
    UGT-1I
    Short name:
    UGT1I
    UDP-glucuronosyltransferase 1A9
    lugP4
    Gene namesi
    Name:UGT1A9
    Synonyms:GNT1, UGT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:12541. UGT1A9.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProt
    2. endoplasmic reticulum membrane Source: Reactome
    3. extracellular vesicular exosome Source: UniProt
    4. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA419.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2525Sequence AnalysisAdd
    BLAST
    Chaini26 – 530505UDP-glucuronosyltransferase 1-9PRO_0000036008Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi71 – 711N-linked (GlcNAc...)1 Publication
    Modified residuei99 – 991N6-succinyllysineBy similarity
    Glycosylationi292 – 2921N-linked (GlcNAc...)1 Publication
    Glycosylationi344 – 3441N-linked (GlcNAc...)1 Publication

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PRIDEiO60656.

    PTM databases

    PhosphoSiteiO60656.

    Expressioni

    Tissue specificityi

    Liver. Isoform 1 and isoform 2 are expressed in liver, kidney, colon, esophagus and small intestine.1 Publication

    Gene expression databases

    BgeeiO60656.
    GenevestigatoriO60656.

    Interactioni

    Subunit structurei

    Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10.1 Publication

    Protein-protein interaction databases

    IntActiO60656. 7 interactions.
    STRINGi9606.ENSP00000346768.

    Structurei

    3D structure databases

    ProteinModelPortaliO60656.
    SMRiO60656. Positions 222-446.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei488 – 50417HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the UDP-glycosyltransferase family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOGENOMiHOG000220832.
    HOVERGENiHBG004033.
    KOiK00699.
    OMAiLISHTSI.
    OrthoDBiEOG7GBFWS.
    PhylomeDBiO60656.
    TreeFamiTF315472.

    Family and domain databases

    InterProiIPR002213. UDP_glucos_trans.
    [Graphical view]
    PANTHERiPTHR11926. PTHR11926. 1 hit.
    PfamiPF00201. UDPGT. 1 hit.
    [Graphical view]
    PROSITEiPS00375. UDPGT. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O60656-1) [UniParc]FASTAAdd to Basket

    Also known as: i1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MACTGWTSPL PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MRSVVEKLIL    50
    RGHEVVVVMP EVSWQLGRSL NCTVKTYSTS YTLEDLDREF KAFAHAQWKA 100
    QVRSIYSLLM GSYNDIFDLF FSNCRSLFKD KKLVEYLKES SFDAVFLDPF 150
    DNCGLIVAKY FSLPSVVFAR GILCHYLEEG AQCPAPLSYV PRILLGFSDA 200
    MTFKERVRNH IMHLEEHLLC HRFFKNALEI ASEILQTPVT EYDLYSHTSI 250
    WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY INASGEHGIV 300
    VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK 350
    WLPQNDLLGH PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR 400
    METKGAGVTL NVLEMTSEDL ENALKAVIND KSYKENIMRL SSLHKDRPVE 450
    PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW YQYHSLDVIG FLLAVVLTVA 500
    FITFKCCAYG YRKCLGKKGR VKKAHKSKTH 530
    Length:530
    Mass (Da):59,941
    Last modified:August 1, 1998 - v1
    Checksum:iC417B9E86B403078
    GO
    Isoform 2 (identifier: O60656-2) [UniParc]FASTAAdd to Basket

    Also known as: i2, UGT1A9s

    The sequence of this isoform differs from the canonical sequence as follows:
         432-530: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

    Show »
    Length:441
    Mass (Da):49,718
    Checksum:i2A0722CDA3A85E9E
    GO

    Sequence cautioni

    The sequence AAB19791.2 differs from that shown. Reason: Frameshift at positions 59 and 82.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti29 – 291L → V in AAB19791. (PubMed:1910331)Curated
    Sequence conflicti200 – 2001A → D in AAB19791. (PubMed:1910331)Curated
    Sequence conflicti279 – 2824QGKP → ERKA in AAB19791. (PubMed:1910331)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti33 – 331M → T.1 Publication
    Corresponds to variant rs72551330 [ dbSNP | Ensembl ].
    VAR_058587
    Natural varianti442 – 4421S → I in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036035

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2. CuratedVSP_053965Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S55985 mRNA. Translation: AAB19791.2. Frameshift.
    AF056188 mRNA. Translation: AAC31425.1.
    AF297093 Genomic DNA. Translation: AAG30418.1.
    AC006985 Genomic DNA. No translation available.
    AC019072 Genomic DNA. No translation available.
    BC058844 mRNA. Translation: AAH58844.1.
    AF297091 Genomic DNA. Translation: AAG29816.1.
    DQ364246 mRNA. Translation: ABC96770.1.
    CCDSiCCDS2505.1. [O60656-1]
    PIRiS17512.
    RefSeqiNP_066307.1. NM_021027.2. [O60656-1]
    UniGeneiHs.554822.

    Genome annotation databases

    EnsembliENST00000354728; ENSP00000346768; ENSG00000241119. [O60656-1]
    GeneIDi54600.
    KEGGihsa:54600.
    UCSCiuc002vus.3. human. [O60656-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S55985 mRNA. Translation: AAB19791.2 . Frameshift.
    AF056188 mRNA. Translation: AAC31425.1 .
    AF297093 Genomic DNA. Translation: AAG30418.1 .
    AC006985 Genomic DNA. No translation available.
    AC019072 Genomic DNA. No translation available.
    BC058844 mRNA. Translation: AAH58844.1 .
    AF297091 Genomic DNA. Translation: AAG29816.1 .
    DQ364246 mRNA. Translation: ABC96770.1 .
    CCDSi CCDS2505.1. [O60656-1 ]
    PIRi S17512.
    RefSeqi NP_066307.1. NM_021027.2. [O60656-1 ]
    UniGenei Hs.554822.

    3D structure databases

    ProteinModelPortali O60656.
    SMRi O60656. Positions 222-446.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi O60656. 7 interactions.
    STRINGi 9606.ENSP00000346768.

    Chemistry

    BindingDBi O60656.
    ChEMBLi CHEMBL1743319.
    DrugBanki DB00494. Entacapone.
    DB00749. Etodolac.
    DB00328. Indomethacin.
    DB00762. Irinotecan.
    DB01024. Mycophenolic acid.
    DB00219. Oxyphenonium.
    DB00818. Propofol.
    DB00398. Sorafenib.

    Protein family/group databases

    CAZyi GT1. Glycosyltransferase Family 1.

    PTM databases

    PhosphoSitei O60656.

    Proteomic databases

    PRIDEi O60656.

    Protocols and materials databases

    DNASUi 54600.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000354728 ; ENSP00000346768 ; ENSG00000241119 . [O60656-1 ]
    GeneIDi 54600.
    KEGGi hsa:54600.
    UCSCi uc002vus.3. human. [O60656-1 ]

    Organism-specific databases

    CTDi 54600.
    GeneCardsi GC02P234580.
    HGNCi HGNC:12541. UGT1A9.
    MIMi 191740. gene.
    606434. gene.
    neXtProti NX_O60656.
    PharmGKBi PA419.
    GenAtlasi Search...

    Phylogenomic databases

    HOGENOMi HOG000220832.
    HOVERGENi HBG004033.
    KOi K00699.
    OMAi LISHTSI.
    OrthoDBi EOG7GBFWS.
    PhylomeDBi O60656.
    TreeFami TF315472.

    Enzyme and pathway databases

    BRENDAi 2.4.1.17. 2681.
    Reactomei REACT_116145. PPARA activates gene expression.
    REACT_6784. Glucuronidation.
    SABIO-RK O60656.

    Miscellaneous databases

    GeneWikii UGT1A9.
    GenomeRNAii 54600.
    NextBioi 35481510.
    PROi O60656.
    SOURCEi Search...

    Gene expression databases

    Bgeei O60656.
    Genevestigatori O60656.

    Family and domain databases

    InterProi IPR002213. UDP_glucos_trans.
    [Graphical view ]
    PANTHERi PTHR11926. PTHR11926. 1 hit.
    Pfami PF00201. UDPGT. 1 hit.
    [Graphical view ]
    PROSITEi PS00375. UDPGT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family."
      Wooster R., Sutherland L., Ebner T., Clarke D., da Cruz e Silva O., Burchell B.
      Biochem. J. 278:465-469(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    2. "Human phenol metabolizing UDP-glucuronosyltransferase."
      Ciotti M., Potter C., Owens I.S.
      Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Liver.
    3. "Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1 gene complex locus."
      Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K., Kubota S., Carvalho S., Pennington M.W., Owens I.S., Popescu N.C.
      Pharmacogenetics 11:357-368(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Kidney.
    6. "Human phenol UDP-glucuronosyltransferase (UGT1A9) gene isozyme exon 1."
      Owens I.S., Gong Q., Cho J.W., Potter C., Gholami N.
      Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-285.
    7. Guillemette C., Levesque E., Girard H., Bernard O.
      Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
    8. "Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity."
      Girard H., Levesque E., Bellemare J., Journault K., Caillier B., Guillemette C.
      Pharmacogenet. Genomics 17:1077-1089(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    9. "Structure and concentration changes affect characterization of UGT isoform-specific metabolism of isoflavones."
      Tang L., Singh R., Liu Z., Hu M.
      Mol. Pharm. 6:1466-1482(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro."
      Bellemare J., Rouleau M., Girard H., Harvey M., Guillemette C.
      Drug Metab. Dispos. 38:1785-1789(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), SUBUNIT.
    11. "N-Glycosylation plays a role in protein folding of human UGT1A9."
      Nakajima M., Koga T., Sakai H., Yamanaka H., Fujiwara R., Yokoi T.
      Biochem. Pharmacol. 79:1165-1172(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-71; ASN-292 AND ASN-344.
    12. Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-442.
    13. "Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population."
      Menard V., Girard H., Harvey M., Perusse L., Guillemette C.
      Hum. Mutat. 30:677-687(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT THR-33.

    Entry informationi

    Entry nameiUD19_HUMAN
    AccessioniPrimary (citable) accession number: O60656
    Secondary accession number(s): B8K285, P36509, Q9HAX0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 11, 2003
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 126 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    The gene is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3