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P35503 (UD13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. 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 1-3

Short name=UDPGT 1-3
Short name=UGT1*3
Short name=UGT1-03
Short name=UGT1.3
EC=2.4.1.17
Alternative name(s):
UDP-glucuronosyltransferase 1-C
Short name=UGT-1C
Short name=UGT1C
UDP-glucuronosyltransferase 1A3
Gene names
Name:UGT1A3
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length534 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. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. Ref.5

Catalytic activity

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

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, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10. Ref.6

Subcellular location

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

Tissue specificity

Isoform 1 and isoform 2 are expressed in liver, kidney, colon and small intestine. Isoform 1 but not isoform 2 is expressed in esophagus. Ref.7

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35503-1)

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: P35503-3)

Also known as: i2; UGT1A3s;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 534506UDP-glucuronosyltransferase 1-3
PRO_0000036002

Regions

Transmembrane492 – 50817Helical; Potential

Amino acid modifications

Glycosylation1191N-linked (GlcNAc...) Potential
Glycosylation1421N-linked (GlcNAc...) Ref.8
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence436 – 53499SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053959
Natural variant61Q → R.
Corresponds to variant rs28898617 [ dbSNP | Ensembl ].
VAR_052445
Natural variant111W → R. Ref.9
Corresponds to variant rs3821242 [ dbSNP | Ensembl ].
VAR_052446
Natural variant451R → W.
Corresponds to variant rs45625338 [ dbSNP | Ensembl ].
VAR_052447
Natural variant471V → A. Ref.9
Corresponds to variant rs6431625 [ dbSNP | Ensembl ].
VAR_052448
Natural variant491R → W.
Corresponds to variant rs45595237 [ dbSNP | Ensembl ].
VAR_052449
Natural variant781T → I.
Corresponds to variant rs28898618 [ dbSNP | Ensembl ].
VAR_052450
Natural variant1141M → I.
Corresponds to variant rs28898619 [ dbSNP | Ensembl ].
VAR_052451
Natural variant1441T → I.
Corresponds to variant rs13406898 [ dbSNP | Ensembl ].
VAR_052452
Natural variant1581A → V. Ref.9
Corresponds to variant rs61764030 [ dbSNP | Ensembl ].
VAR_058583
Natural variant2701M → V. Ref.9
Corresponds to variant rs45449995 [ dbSNP | Ensembl ].
VAR_052453

Sequences

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

Last modified June 1, 1994. Version 1.
Checksum: 9C5833652A4D9B3D

FASTA53460,338
        10         20         30         40         50         60 
MATGLQVPLP WLATGLLLLL SVQPWAESGK VLVVPIDGSH WLSMREVLRE LHARGHQAVV 

        70         80         90        100        110        120 
LTPEVNMHIK EENFFTLTTY AISWTQDEFD RHVLGHTQLY FETEHFLKKF FRSMAMLNNM 

       130        140        150        160        170        180 
SLVYHRSCVE LLHNEALIRH LNATSFDVVL TDPVNLCAAV LAKYLSIPTV FFLRNIPCDL 

       190        200        210        220        230        240 
DFKGTQCPNP SSYIPRLLTT NSDHMTFMQR VKNMLYPLAL SYICHAFSAP YASLASELFQ 

       250        260        270        280        290        300 
REVSVVDILS HASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANRKPLSQE FEAYINASGE 

       310        320        330        340        350        360 
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT ILVKWLPQND 

       370        380        390        400        410        420 
LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD NAKRMETKGA GVTLNVLEMT 

       430        440        450        460        470        480 
SEDLENALKA VINDKSYKEN IMRLSSLHKD RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH 

       490        500        510        520        530 
DLTWYQYHSL DVIGFLLAVV LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH 

« Hide

Isoform 2 (i2) (UGT1A3s) [UniParc].

Checksum: C30BB9928D337B4F
Show »

FASTA44550,115

References

« Hide 'large scale' references
[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. 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].
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRD42586.
RefSeqNP_061966.1. NM_019093.2.
UniGeneHs.554822.

3D structure databases

ProteinModelPortalP35503.
SMRP35503. Positions 285-445.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000418532.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteP35503.

Proteomic databases

PaxDbP35503.
PRIDEP35503.

Protocols and materials databases

DNASU54659.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000482026; ENSP00000418532; ENSG00000243135. [P35503-1]
GeneID54659.
KEGGhsa:54659.
UCSCuc002vuy.3. human. [P35503-1]

Organism-specific databases

CTD54659.
GeneCardsGC02P234637.
HGNCHGNC:12535. UGT1A3.
MIM191740. gene.
606428. gene.
neXtProtNX_P35503.
PharmGKBPA37178.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1819.
HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMAFFRSMAM.
OrthoDBEOG7GBFWS.
PhylomeDBP35503.
TreeFamTF315472.

Enzyme and pathway databases

BioCycMetaCyc:UGT1A3-MONOMER.
BRENDA2.4.1.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP35503.

Gene expression databases

BgeeP35503.
GenevestigatorP35503.

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

GeneWikiUGT1A3.
GenomeRNAi54659.
NextBio57192.
PROP35503.
SOURCESearch...

Entry information

Entry nameUD13_HUMAN
AccessionPrimary (citable) accession number: P35503
Secondary accession number(s): B8K287
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 16, 2014
This is version 126 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