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P35503

- UD13_HUMAN

UniProt

P35503 - UD13_HUMAN

Protein

UDP-glucuronosyltransferase 1-3

Gene

UGT1A3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Jun 1994)
      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. 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.

    GO - Molecular functioni

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

    GO - Biological processi

    1. cellular glucuronidation Source: UniProt
    2. flavonoid glucuronidation Source: BHF-UCL
    3. metabolic process Source: ProtInc
    4. retinoic acid metabolic process Source: BHF-UCL
    5. xenobiotic glucuronidation Source: BHF-UCL

    Keywords - Molecular functioni

    Glycosyltransferase, Transferase

    Enzyme and pathway databases

    BioCyciMetaCyc:UGT1A3-MONOMER.
    BRENDAi2.4.1.17. 2681.
    ReactomeiREACT_6784. Glucuronidation.
    SABIO-RKP35503.

    Protein family/group databases

    CAZyiGT1. Glycosyltransferase Family 1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    UDP-glucuronosyltransferase 1-3 (EC:2.4.1.17)
    Short name:
    UDPGT 1-3
    Short name:
    UGT1*3
    Short name:
    UGT1-03
    Short name:
    UGT1.3
    Alternative name(s):
    UDP-glucuronosyltransferase 1-C
    Short name:
    UGT-1C
    Short name:
    UGT1C
    UDP-glucuronosyltransferase 1A3
    Gene namesi
    Name:UGT1A3
    Synonyms:GNT1, UGT1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:12535. UGT1A3.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum Source: UniProt
    2. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA37178.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2828Sequence AnalysisAdd
    BLAST
    Chaini29 – 534506UDP-glucuronosyltransferase 1-3PRO_0000036002Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi119 – 1191N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi142 – 1421N-linked (GlcNAc...)1 Publication
    Glycosylationi296 – 2961N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi348 – 3481N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiP35503.
    PRIDEiP35503.

    PTM databases

    PhosphoSiteiP35503.

    Expressioni

    Tissue specificityi

    Isoform 1 and isoform 2 are expressed in liver, kidney, colon and small intestine. Isoform 1 but not isoform 2 is expressed in esophagus.1 Publication

    Gene expression databases

    BgeeiP35503.
    GenevestigatoriP35503.

    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, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10.1 Publication

    Protein-protein interaction databases

    IntActiP35503. 7 interactions.
    STRINGi9606.ENSP00000418532.

    Structurei

    3D structure databases

    ProteinModelPortaliP35503.
    SMRiP35503. Positions 285-445.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei492 – 50817HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the UDP-glycosyltransferase family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1819.
    HOGENOMiHOG000220832.
    HOVERGENiHBG004033.
    KOiK00699.
    OMAiFFRSMAM.
    OrthoDBiEOG7GBFWS.
    PhylomeDBiP35503.
    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: P35503-1) [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

    MATGLQVPLP WLATGLLLLL SVQPWAESGK VLVVPIDGSH WLSMREVLRE    50
    LHARGHQAVV LTPEVNMHIK EENFFTLTTY AISWTQDEFD RHVLGHTQLY 100
    FETEHFLKKF FRSMAMLNNM SLVYHRSCVE LLHNEALIRH LNATSFDVVL 150
    TDPVNLCAAV LAKYLSIPTV FFLRNIPCDL DFKGTQCPNP SSYIPRLLTT 200
    NSDHMTFMQR VKNMLYPLAL SYICHAFSAP YASLASELFQ REVSVVDILS 250
    HASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANRKPLSQE FEAYINASGE 300
    HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT 350
    ILVKWLPQND LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD 400
    NAKRMETKGA GVTLNVLEMT SEDLENALKA VINDKSYKEN IMRLSSLHKD 450
    RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH DLTWYQYHSL DVIGFLLAVV 500
    LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH 534
    Length:534
    Mass (Da):60,338
    Last modified:June 1, 1994 - v1
    Checksum:i9C5833652A4D9B3D
    GO
    Isoform 2 (identifier: P35503-3) [UniParc]FASTAAdd to Basket

    Also known as: i2, UGT1A3s

    The sequence of this isoform differs from the canonical sequence as follows:
         436-534: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

    Show »
    Length:445
    Mass (Da):50,115
    Checksum:iC30BB9928D337B4F
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti6 – 61Q → R.
    Corresponds to variant rs28898617 [ dbSNP | Ensembl ].
    VAR_052445
    Natural varianti11 – 111W → R.1 Publication
    Corresponds to variant rs3821242 [ dbSNP | Ensembl ].
    VAR_052446
    Natural varianti45 – 451R → W.
    Corresponds to variant rs45625338 [ dbSNP | Ensembl ].
    VAR_052447
    Natural varianti47 – 471V → A.1 Publication
    Corresponds to variant rs6431625 [ dbSNP | Ensembl ].
    VAR_052448
    Natural varianti49 – 491R → W.
    Corresponds to variant rs45595237 [ dbSNP | Ensembl ].
    VAR_052449
    Natural varianti78 – 781T → I.
    Corresponds to variant rs28898618 [ dbSNP | Ensembl ].
    VAR_052450
    Natural varianti114 – 1141M → I.
    Corresponds to variant rs28898619 [ dbSNP | Ensembl ].
    VAR_052451
    Natural varianti144 – 1441T → I.
    Corresponds to variant rs13406898 [ dbSNP | Ensembl ].
    VAR_052452
    Natural varianti158 – 1581A → V.1 Publication
    Corresponds to variant rs61764030 [ dbSNP | Ensembl ].
    VAR_058583
    Natural varianti270 – 2701M → V.1 Publication
    Corresponds to variant rs45449995 [ dbSNP | Ensembl ].
    VAR_052453

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei436 – 53499SYKEN…KSKTH → RKKQQSGRQM in isoform 2. CuratedVSP_053959Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84127 Genomic DNA. Translation: AAA92020.1.
    M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
    AF297093 Genomic DNA. Translation: AAG30423.1.
    AC006985 Genomic DNA. No translation available.
    AC114812 Genomic DNA. No translation available.
    DQ364248 mRNA. Translation: ABC96772.1.
    CCDSiCCDS2509.1. [P35503-1]
    PIRiD42586.
    RefSeqiNP_061966.1. NM_019093.2. [P35503-1]
    UniGeneiHs.554822.

    Genome annotation databases

    EnsembliENST00000482026; ENSP00000418532; ENSG00000243135. [P35503-1]
    ENST00000609767; ENSP00000476805; ENSG00000243135. [P35503-1]
    GeneIDi54659.
    KEGGihsa:54659.
    UCSCiuc002vuy.3. human. [P35503-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M84127 Genomic DNA. Translation: AAA92020.1 .
    M84124 , M84122 , M84123 Genomic DNA. Translation: AAA61247.1 . Sequence problems.
    AF297093 Genomic DNA. Translation: AAG30423.1 .
    AC006985 Genomic DNA. No translation available.
    AC114812 Genomic DNA. No translation available.
    DQ364248 mRNA. Translation: ABC96772.1 .
    CCDSi CCDS2509.1. [P35503-1 ]
    PIRi D42586.
    RefSeqi NP_061966.1. NM_019093.2. [P35503-1 ]
    UniGenei Hs.554822.

    3D structure databases

    ProteinModelPortali P35503.
    SMRi P35503. Positions 285-445.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P35503. 7 interactions.
    STRINGi 9606.ENSP00000418532.

    Protein family/group databases

    CAZyi GT1. Glycosyltransferase Family 1.

    PTM databases

    PhosphoSitei P35503.

    Proteomic databases

    PaxDbi P35503.
    PRIDEi P35503.

    Protocols and materials databases

    DNASUi 54659.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000482026 ; ENSP00000418532 ; ENSG00000243135 . [P35503-1 ]
    ENST00000609767 ; ENSP00000476805 ; ENSG00000243135 . [P35503-1 ]
    GeneIDi 54659.
    KEGGi hsa:54659.
    UCSCi uc002vuy.3. human. [P35503-1 ]

    Organism-specific databases

    CTDi 54659.
    GeneCardsi GC02P234637.
    HGNCi HGNC:12535. UGT1A3.
    MIMi 191740. gene.
    606428. gene.
    neXtProti NX_P35503.
    PharmGKBi PA37178.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1819.
    HOGENOMi HOG000220832.
    HOVERGENi HBG004033.
    KOi K00699.
    OMAi FFRSMAM.
    OrthoDBi EOG7GBFWS.
    PhylomeDBi P35503.
    TreeFami TF315472.

    Enzyme and pathway databases

    BioCyci MetaCyc:UGT1A3-MONOMER.
    BRENDAi 2.4.1.17. 2681.
    Reactomei REACT_6784. Glucuronidation.
    SABIO-RK P35503.

    Miscellaneous databases

    GeneWikii UGT1A3.
    GenomeRNAii 54659.
    NextBioi 35481511.
    PROi P35503.
    SOURCEi Search...

    Gene expression databases

    Bgeei P35503.
    Genevestigatori P35503.

    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. "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini."
      Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T., Owens I.S.
      J. Biol. Chem. 267:3257-3261(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "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].
    3. "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].
    4. Guillemette C., Levesque E., Girard H., Bernard O.
      Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    5. "The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan."
      Alonen A., Finel M., Kostiainen R.
      Biochem. Pharmacol. 76:763-772(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "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: SUBUNIT.
    7. "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: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
    8. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142.
      Tissue: Liver.
    9. "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: VARIANTS ARG-11; ALA-47; VAL-158 AND VAL-270.

    Entry informationi

    Entry nameiUD13_HUMAN
    AccessioniPrimary (citable) accession number: P35503
    Secondary accession number(s): B8K287
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: June 1, 1994
    Last modified: October 1, 2014
    This is version 131 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