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P35503

- UD13_HUMAN

UniProt

P35503 - UD13_HUMAN

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Protein

UDP-glucuronosyltransferase 1-3

Gene

UGT1A3

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. 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
Complete GO annotation...

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

Topology

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

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProt
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

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.
ExpressionAtlasiP35503. baseline.
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...

Family & Domainsi

Sequence similaritiesi

Belongs to the UDP-glycosyltransferase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1819.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiP35503.
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

        10         20         30         40         50
MATGLQVPLP WLATGLLLLL SVQPWAESGK VLVVPIDGSH WLSMREVLRE
60 70 80 90 100
LHARGHQAVV LTPEVNMHIK EENFFTLTTY AISWTQDEFD RHVLGHTQLY
110 120 130 140 150
FETEHFLKKF FRSMAMLNNM SLVYHRSCVE LLHNEALIRH LNATSFDVVL
160 170 180 190 200
TDPVNLCAAV LAKYLSIPTV FFLRNIPCDL DFKGTQCPNP SSYIPRLLTT
210 220 230 240 250
NSDHMTFMQR VKNMLYPLAL SYICHAFSAP YASLASELFQ REVSVVDILS
260 270 280 290 300
HASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANRKPLSQE FEAYINASGE
310 320 330 340 350
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT
360 370 380 390 400
ILVKWLPQND LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD
410 420 430 440 450
NAKRMETKGA GVTLNVLEMT SEDLENALKA VINDKSYKEN IMRLSSLHKD
460 470 480 490 500
RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH DLTWYQYHSL DVIGFLLAVV
510 520 530
LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH
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:
EMBLi
GenBanki
DDBJi
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. [P35503-3]
GeneIDi54659.
KEGGihsa:54659.
UCSCiuc002vuy.3. human. [P35503-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Chemistry

DrugBanki DB01076. Atorvastatin.
DB00796. Candesartan.
DB00434. Cyproheptadine.
DB06210. Eltrombopag.
DB00749. Etodolac.
DB00973. Ezetimibe.
DB04953. Ezogabine.
DB01544. Flunitrazepam.
DB00712. Flurbiprofen.
DB01095. Fluvastatin.
DB01050. Ibuprofen.
DB01029. Irbesartan.
DB00555. Lamotrigine.
DB00678. Losartan.
DB00227. Lovastatin.
DB01252. Mitiglinide.
DB00295. Morphine.
DB08860. Pitavastatin.
DB00641. Simvastatin.
DB00313. Valproic Acid.

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 . [P35503-3 ]
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.
GeneTreei ENSGT00760000118949.
HOGENOMi HOG000220832.
HOVERGENi HBG004033.
InParanoidi P35503.
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.
ExpressionAtlasi P35503. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 132 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