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O60656 (UD19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
UDP-glucuronosyltransferase 1-9

Short name=UDPGT 1-9
Short name=UGT1*9
Short name=UGT1-09
Short name=UGT1.9
EC=2.4.1.17
Alternative name(s):
UDP-glucuronosyltransferase 1-I
Short name=UGT-1I
Short name=UGT1I
UDP-glucuronosyltransferase 1A9
lugP4
Gene names
Name:UGT1A9
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length530 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform hasspecificity for phenols. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. Ref.8 Ref.9 Ref.10

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. Ref.8 Ref.10

Subunit structure

Isoform 1 interacts with isoform 2/i2suggesting 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. Ref.10

Subcellular location

Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential.

Tissue specificity

Liver. Isoform 1 and isoform 2 are expressed in liver, kidney, colon, esophagus and small intestine. Ref.8

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.

Sequence similarities

Belongs to the UDP-glycosyltransferase family.

Sequence caution

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

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionGlycosyltransferase
Transferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid metabolic process

Traceable author statement. Source: Reactome

drug metabolic process

Inferred from direct assay Ref.10. Source: BHF-UCL

flavone metabolic process

Inferred from direct assay PubMed 18052087. Source: BHF-UCL

flavonoid glucuronidation

Inferred from direct assay PubMed 20056724. Source: BHF-UCL

metabolic process

Traceable author statement Ref.1. Source: ProtInc

negative regulation of catalytic activity

Inferred from direct assay Ref.10. Source: GOC

negative regulation of cellular glucuronidation

Inferred from direct assay Ref.8Ref.10. Source: UniProtKB

negative regulation of fatty acid metabolic process

Inferred from direct assay Ref.10. Source: BHF-UCL

retinoic acid metabolic process

Inferred by curator PubMed 20308471. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

xenobiotic glucuronidation

Inferred from direct assay PubMed 20056724. Source: BHF-UCL

xenobiotic metabolic process

Inferred from direct assay Ref.1. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionenzyme binding

Inferred from direct assay Ref.10. Source: BHF-UCL

enzyme inhibitor activity

Inferred from direct assay Ref.10. Source: BHF-UCL

glucuronosyltransferase activity

Inferred from direct assay PubMed 18052087PubMed 20056724PubMed 20308471. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction. Source: BHF-UCL

retinoic acid binding

Inferred from direct assay PubMed 20308471. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O60656-1)

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.
Isoform 2 (identifier: O60656-2)

Also known as: i2; UGT1A9s;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 530505UDP-glucuronosyltransferase 1-9
PRO_0000036008

Regions

Transmembrane488 – 50417Helical; Potential

Amino acid modifications

Modified residue991N6-succinyllysine By similarity
Glycosylation711N-linked (GlcNAc...) Ref.11
Glycosylation2921N-linked (GlcNAc...) Ref.11
Glycosylation3441N-linked (GlcNAc...) Ref.11

Natural variations

Alternative sequence432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053965
Natural variant331M → T. Ref.13
Corresponds to variant rs72551330 [ dbSNP | Ensembl ].
VAR_058587
Natural variant4421S → I in a breast cancer sample; somatic mutation. Ref.12
VAR_036035

Experimental info

Sequence conflict291L → V in AAB19791. Ref.1
Sequence conflict2001A → D in AAB19791. Ref.1
Sequence conflict279 – 2824QGKP → ERKA in AAB19791. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (i1) [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: C417B9E86B403078

FASTA53059,941
        10         20         30         40         50         60 
MACTGWTSPL PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MRSVVEKLIL RGHEVVVVMP 

        70         80         90        100        110        120 
EVSWQLGRSL NCTVKTYSTS YTLEDLDREF KAFAHAQWKA QVRSIYSLLM GSYNDIFDLF 

       130        140        150        160        170        180 
FSNCRSLFKD KKLVEYLKES SFDAVFLDPF DNCGLIVAKY FSLPSVVFAR GILCHYLEEG 

       190        200        210        220        230        240 
AQCPAPLSYV PRILLGFSDA MTFKERVRNH IMHLEEHLLC HRFFKNALEI ASEILQTPVT 

       250        260        270        280        290        300 
EYDLYSHTSI WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY INASGEHGIV 

       310        320        330        340        350        360 
VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK WLPQNDLLGH 

       370        380        390        400        410        420 
PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR METKGAGVTL NVLEMTSEDL 

       430        440        450        460        470        480 
ENALKAVIND KSYKENIMRL SSLHKDRPVE PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW 

       490        500        510        520        530 
YQYHSLDVIG FLLAVVLTVA FITFKCCAYG YRKCLGKKGR VKKAHKSKTH 

« Hide

Isoform 2 (i2) (UGT1A9s) [UniParc].

Checksum: 2A0722CDA3A85E9E
Show »

FASTA44149,718

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS2505.1. [O60656-1]
PIRS17512.
RefSeqNP_066307.1. NM_021027.2. [O60656-1]
UniGeneHs.554822.

3D structure databases

ProteinModelPortalO60656.
SMRO60656. Positions 222-446.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000346768.

Chemistry

BindingDBO60656.
ChEMBLCHEMBL1743319.
DrugBankDB00494. Entacapone.
DB00749. Etodolac.
DB00328. Indomethacin.
DB00762. Irinotecan.
DB01024. Mycophenolic acid.
DB00219. Oxyphenonium.
DB00818. Propofol.
DB00398. Sorafenib.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteO60656.

Proteomic databases

PRIDEO60656.

Protocols and materials databases

DNASU54600.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354728; ENSP00000346768; ENSG00000241119. [O60656-1]
GeneID54600.
KEGGhsa:54600.
UCSCuc002vus.3. human. [O60656-1]

Organism-specific databases

CTD54600.
GeneCardsGC02P234580.
HGNCHGNC:12541. UGT1A9.
MIM191740. gene.
606434. gene.
neXtProtNX_O60656.
PharmGKBPA419.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMALISHTSI.
OrthoDBEOG7GBFWS.
PhylomeDBO60656.
TreeFamTF315472.

Enzyme and pathway databases

BRENDA2.4.1.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKO60656.

Gene expression databases

BgeeO60656.
GenevestigatorO60656.

Family and domain databases

InterProIPR002213. UDP_glucos_trans.
[Graphical view]
PANTHERPTHR11926. PTHR11926. 1 hit.
PfamPF00201. UDPGT. 1 hit.
[Graphical view]
PROSITEPS00375. UDPGT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUGT1A9.
GenomeRNAi54600.
NextBio35481510.
PROO60656.
SOURCESearch...

Entry information

Entry nameUD19_HUMAN
AccessionPrimary (citable) accession number: O60656
Secondary accession number(s): B8K285, P36509, Q9HAX0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM