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O60656

- UD19_HUMAN

UniProt

O60656 - UD19_HUMAN

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Protein

UDP-glucuronosyltransferase 1-9

Gene
UGT1A9, GNT1, UGT1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 1.3 Publications

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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei488 – 50417Helical; Reviewed predictionAdd
BLAST

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
Complete GO annotation...

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 – 2525 Reviewed predictionAdd
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-succinyllysine By 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.

Family & Domainsi

Sequence similaritiesi

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.

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. VSP_053965Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti29 – 291L → V in AAB19791. 1 Publication
Sequence conflicti200 – 2001A → D in AAB19791. 1 Publication
Sequence conflicti279 – 2824QGKP → ERKA in AAB19791. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 125 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

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