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P22309 (UD11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. 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·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
UDP-glucuronosyltransferase 1-1

Short name=UDPGT 1-1
Short name=UGT1*1
Short name=UGT1-01
Short name=UGT1.1
EC=2.4.1.17
Alternative name(s):
Bilirubin-specific UDPGT isozyme 1
Short name=hUG-BR1
UDP-glucuronosyltransferase 1-A
Short name=UGT-1A
Short name=UGT1A
UDP-glucuronosyltransferase 1A1
Gene names
Name:UGT1A1
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length533 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 glucuronidatesbilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. Ref.9 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 UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Ref.8 Ref.15

Subcellular location

Isoform 1: Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential Ref.8.

Isoform 2: Endoplasmic reticulum Ref.8.

Tissue specificity

Isoform 1 and isoform 2 are expressed in liver, colon and small intestine. Isoform 2 but not isoform 1 is expressed in kidney. Isoform 1 and isoform 2 are not expressed in esophagus. Not expressed in skin. Ref.2 Ref.8 Ref.10

Polymorphism

Genetic variation in UGT1A1 defines the bilirubin serum levels quantitative trait locus 1 (BILIQTL1) [MIM:601816]. Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism.

Involvement in disease

Gilbert syndrome (GILBS) [MIM:143500]: Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.27 Ref.28 Ref.32

Transient familial neonatal hyperbilirubinemia (HBLRTFN) [MIM:237900]: A condition characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants.
Note: The disease may be caused by mutations affecting the gene represented in this entry. The defect has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unclear. Defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. Mutations are identical to those detected in patients with Gilbert syndrome, a risk factor of neonatal non-physiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia. Ref.29

Crigler-Najjar syndrome 1 (CN1) [MIM:218800]: Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.16 Ref.19 Ref.20 Ref.21 Ref.22 Ref.28 Ref.34 Ref.35

Crigler-Najjar syndrome 2 (CN2) [MIM:606785]: Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.12 Ref.17 Ref.18 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.31 Ref.33 Ref.34 Ref.35

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.

Biophysicochemical properties

Kinetic parameters:

KM=0.26 µM for bilirubin Ref.9

Vmax=1080 pmol/min/mg enzyme with bilirubin as substrate

Sequence caution

The sequence AAA61247.1 differs from that shown. Reason: Erroneous gene model prediction.

The sequence AAF03522.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionGlycosyltransferase
Transferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processacute-phase response

Inferred from electronic annotation. Source: Ensembl

bilirubin conjugation

Traceable author statement Ref.2. Source: ProtInc

biphenyl catabolic process

Inferred from electronic annotation. Source: Ensembl

cellular glucuronidation

Traceable author statement. Source: Reactome

cellular response to ethanol

Inferred from electronic annotation. Source: Ensembl

cellular response to glucocorticoid stimulus

Inferred from electronic annotation. Source: Ensembl

digestion

Non-traceable author statement Ref.1. Source: ProtInc

drug metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

estrogen metabolic process

Traceable author statement PubMed 8780690. Source: ProtInc

flavone metabolic process

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

flavonoid glucuronidation

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

heme catabolic process

Traceable author statement. Source: Reactome

heterocycle metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

liver development

Inferred from electronic annotation. Source: Ensembl

negative regulation of catalytic activity

Inferred from direct assay PubMed 19996319. Source: GOC

negative regulation of steroid metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

organ regeneration

Inferred from electronic annotation. Source: Ensembl

porphyrin-containing compound metabolic process

Traceable author statement. Source: Reactome

response to drug

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to starvation

Inferred from electronic annotation. Source: Ensembl

retinoic acid metabolic process

Inferred by curator PubMed 20308471. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

xenobiotic glucuronidation

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

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytochrome complex

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionenzyme binding

Inferred from direct assay Ref.15. Source: BHF-UCL

enzyme inhibitor activity

Inferred from direct assay PubMed 19996319. Source: BHF-UCL

glucuronosyltransferase activity

Inferred from direct assay PubMed 18052087PubMed 19996319PubMed 20056724PubMed 20308471. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction Ref.15. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction Ref.15. Source: BHF-UCL

retinoic acid binding

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

steroid binding

Inferred from direct assay PubMed 19996319. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22309-1)

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: P22309-2)

Also known as: i2; UGT1A1s;

The sequence of this isoform differs from the canonical sequence as follows:
     435-533: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 533508UDP-glucuronosyltransferase 1-1
PRO_0000036000

Regions

Transmembrane491 – 50717Helical; Potential

Amino acid modifications

Glycosylation1021N-linked (GlcNAc...) Ref.14
Glycosylation2951N-linked (GlcNAc...) Potential
Glycosylation3471N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence435 – 53399SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053958
Natural variant151L → R in CN2; mutant protein rapidly degraded by the proteasome owing to its mislocalization in the cell. Ref.12 Ref.24 Ref.28 Ref.33
VAR_019410
Natural variant341P → Q in CN2. Ref.34
VAR_026134
Natural variant391H → D in CN1. Ref.28
VAR_026135
Natural variant711G → R in CN2, GILBS and HBLRTFN; has significant residual bilirubin glucuronidation activity of about 25% to 50% of that of the wild-type protein; displays no change in biluribin affinity. Ref.9 Ref.12 Ref.17 Ref.23 Ref.26 Ref.28 Ref.29
Corresponds to variant rs4148323 [ dbSNP | Ensembl ].
VAR_009504
Natural variant831F → L in GILBS; displays less than 10% of wild-type bilirubin glucuronidation activity. Ref.9 Ref.32
Corresponds to variant rs56059937 [ dbSNP | Ensembl ].
VAR_026136
Natural variant1701Missing in CN1 and CN2; has nearly normal activity at pH 7.6 and is inactive at pH 6.4. Ref.19 Ref.22 Ref.28 Ref.34
VAR_007695
Natural variant1711Missing in CN2. Ref.35
VAR_064955
Natural variant1751L → Q in CN2; has low residual bilirubin glucuronidation activity of about 4.6% of that of the wild-type protein. Ref.12 Ref.22 Ref.28 Ref.30
VAR_019411
Natural variant1771C → R in CN1. Ref.22 Ref.28
VAR_007697
Natural variant1911S → F in CN2; has low residual bilirubin glucuronidation activity of about 5.3% of that of the wild-type protein. Ref.12
VAR_064956
Natural variant2091R → W in CN2; has low residual bilirubin glucuronidation activity of about 2.9% of that of the wild-type protein. Ref.12 Ref.22 Ref.26 Ref.28 Ref.34
VAR_007698
Natural variant2251V → G in CN2. Ref.28 Ref.34
Corresponds to variant rs35003977 [ dbSNP | Ensembl ].
VAR_026137
Natural variant2291P → Q in CN2 and GILBS; displays 2-fold decrease in biluribin affinity and 61% of wild-type bilirubin glucuronidation activity. Ref.9 Ref.23 Ref.26 Ref.28
Corresponds to variant rs35350960 [ dbSNP | Ensembl ].
VAR_009505
Natural variant2761G → R in CN1. Ref.22 Ref.28
VAR_007699
Natural variant2791N → Y in CN2. Ref.35
VAR_064957
Natural variant2911E → V in CN1. Ref.28
VAR_026138
Natural variant2921A → V in CN1. Ref.20
VAR_007700
Natural variant2941I → T in GILBS and CN2; 40-55% normal activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype. Ref.25 Ref.28
VAR_026139
Natural variant3081G → E in CN1; no enzyme activity. Ref.20 Ref.21 Ref.28
VAR_007701
Natural variant3311Q → R in CN2; has no residual bilirubin glucuronidation activity. Ref.12 Ref.18 Ref.28
VAR_007702
Natural variant3361R → L in CN1 and CN2. Ref.34
VAR_026140
Natural variant3361R → Q in CN1. Ref.34
VAR_026141
Natural variant3361R → W in CN2; has very low residual bilirubin glucuronidation activity of about 0.4% of that of the wild-type protein. Ref.12 Ref.28 Ref.34
VAR_026142
Natural variant3541W → R in CN2. Ref.34 Ref.35
VAR_026143
Natural variant3571Q → R in CN1. Ref.20 Ref.28 Ref.34
VAR_007703
Natural variant3671R → G in GILBS. Ref.23 Ref.28
Corresponds to variant rs55750087 [ dbSNP | Ensembl ].
VAR_012283
Natural variant3681A → T in CN1. Ref.20 Ref.28
VAR_007704
Natural variant3701I → V in CN2. Ref.35
VAR_064958
Natural variant3751S → F in CN1; no enzyme activity. Ref.16 Ref.21 Ref.22 Ref.28 Ref.34
VAR_007705
Natural variant3761H → R in CN1 and CN2.
VAR_026144
Natural variant3771G → V in CN1 and CN2. Ref.34
VAR_026145
Natural variant3811S → R in CN1. Ref.20 Ref.28
VAR_007706
Natural variant3871P → H in CN2; has no residual bilirubin glucuronidation activity. Ref.12
VAR_064959
Natural variant3871P → S in CN1. Ref.28 Ref.34
VAR_026146
Natural variant3951G → V in CN1; has no residual bilirubin glucuronidation activity. Ref.12 Ref.34 Ref.35
VAR_026147
Natural variant4001N → D in CN2. Ref.31
Corresponds to variant rs28934877 [ dbSNP | Ensembl ].
VAR_019412
Natural variant4011A → P in CN1. Ref.20 Ref.28
VAR_007707
Natural variant4021K → T in CN1; has no residual bilirubin glucuronidation activity; N-glycosylation does take place at this new additional site. Ref.12
VAR_064960
Natural variant4031R → C in CN2. Ref.34
VAR_026148
Natural variant4281K → E in CN1. Ref.20 Ref.28
VAR_007708
Natural variant4431L → P in CN2; has no residual bilirubin glucuronidation activity. Ref.12 Ref.35
VAR_064961
Natural variant4611W → R in CN1 and CN2. Ref.34 Ref.35
VAR_026149
Natural variant4781A → D in CN2. Ref.34
VAR_026150
Natural variant4861Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. Ref.9 Ref.12 Ref.17 Ref.26 Ref.27 Ref.28 Ref.29
VAR_007709
Natural variant5111A → P.
Corresponds to variant rs1042709 [ dbSNP | Ensembl ].
VAR_025355

Sequences

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

Last modified August 1, 1991. Version 1.
Checksum: 19C90231AD0EB547

FASTA53359,591
        10         20         30         40         50         60 
MAVESQGGRP LVLGLLLCVL GPVVSHAGKI LLIPVDGSHW LSMLGAIQQL QQRGHEIVVL 

        70         80         90        100        110        120 
APDASLYIRD GAFYTLKTYP VPFQREDVKE SFVSLGHNVF ENDSFLQRVI KTYKKIKKDS 

       130        140        150        160        170        180 
AMLLSGCSHL LHNKELMASL AESSFDVMLT DPFLPCSPIV AQYLSLPTVF FLHALPCSLE 

       190        200        210        220        230        240 
FEATQCPNPF SYVPRPLSSH SDHMTFLQRV KNMLIAFSQN FLCDVVYSPY ATLASEFLQR 

       250        260        270        280        290        300 
EVTVQDLLSS ASVWLFRSDF VKDYPRPIMP NMVFVGGINC LHQNPLSQEF EAYINASGEH 

       310        320        330        340        350        360 
GIVVFSLGSM VSEIPEKKAM AIADALGKIP QTVLWRYTGT RPSNLANNTI LVKWLPQNDL 

       370        380        390        400        410        420 
LGHPMTRAFI THAGSHGVYE SICNGVPMVM MPLFGDQMDN AKRMETKGAG VTLNVLEMTS 

       430        440        450        460        470        480 
EDLENALKAV INDKSYKENI MRLSSLHKDR PVEPLDLAVF WVEFVMRHKG APHLRPAAHD 

       490        500        510        520        530 
LTWYQYHSLD VIGFLLAVVL TVAFITFKCC AYGYRKCLGK KGRVKKAHKS KTH 

« Hide

Isoform 2 (i2) (UGT1A1s) [UniParc].

Checksum: 71E6711DDEFED403
Show »

FASTA44449,368

References

« Hide 'large scale' references
[1]"Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells."
Ritter J.K., Crawford J.M., Owens I.S.
J. Biol. Chem. 266:1043-1047(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"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], TISSUE SPECIFICITY.
[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]Guillemette C., Levesque E., Girard H., Bernard O.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]"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].
[6]"Analysis of the promoter of human bilirubin UDP-glucuronosyltransferase gene (UGT1*1) in relevance to Gilbert's syndrome."
Ueyama H., Koiwai O., Soeda Y., Sato H., Satoh Y., Ohkubo I., Doida Y.
Hepatol. Res. 9:152-163(1997)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
[7]"A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins."
Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.
Mol. Biol. Cell 13:4456-4469(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPONENT OF A CHAPERONE COMPLEX.
[8]"Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing event at the UGT1A locus."
Levesque E., Girard H., Journault K., Lepine J., Guillemette C.
Hepatology 45:128-138(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
[9]"Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates."
Udomuksorn W., Elliot D.J., Lewis B.C., Mackenzie P.I., Yoovathaworn K., Miners J.O.
Pharmacogenet. Genomics 17:1017-1029(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, SUBSTRATE SPECIFICITY, CHARACTERIZATION OF VARIANTS CN2 ARG-71; LEU-83; GLN-229 AND ASP-486.
[10]"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, CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), TISSUE SPECIFICITY.
[11]"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.
[12]"Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants."
Sneitz N., Bakker C.T., de Knegt R.J., Halley D.J., Finel M., Bosma P.J.
Hum. Mutat. 31:52-59(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBSTRATE SPECIFICITY, VARIANT CN1 THR-402, VARIANTS CN2 ARG-15; ARG-71; PHE-191; TRP-209; TRP-336; HIS-387; PRO-443 AND ASP-486, CHARACTERIZATION OF VARIANT CN1 THR-402, CHARACTERIZATION OF VARIANTS CN2 ARG-71; GLN-175; PHE-191; TRP-209; ARG-331; TRP-336; HIS-387; VAL-395 AND PRO-443.
[13]"Genome-wide association meta-analysis for total serum bilirubin levels."
Johnson A.D., Kavousi M., Smith A.V., Chen M.H., Dehghan A., Aspelund T., Lin J.P., van Duijn C.M., Harris T.B., Cupples L.A., Uitterlinden A.G., Launer L., Hofman A., Rivadeneira F., Stricker B., Yang Q., O'Donnell C.J., Gudnason V., Witteman J.C.
Hum. Mol. Genet. 18:2700-2710(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN BILIQTL1.
[14]"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-102.
Tissue: Liver.
[15]"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.
[16]"Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I."
Bosma P.J., Chowdhury J.R., Huang T.-J., Lahiri P., Elferink R.P.J.O., van Es H.H.G., Lederstein M., Whitington P.F., Jansen P.L.M., Chowdhury N.R.
FASEB J. 6:2859-2863(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN1 PHE-375.
[17]"Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II."
Aono S., Yamada Y., Keino H., Hanada N., Nakagawa T., Sasaoka Y., Yazawa T., Sato H., Koiwai O.
Biochem. Biophys. Res. Commun. 197:1239-1244(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN2 ARG-71 AND ASP-486.
[18]"Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2."
Moghrabi N., Clarke D.J., Boxer M., Burchell B.
Genomics 18:171-173(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 ARG-331.
[19]"A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase."
Ritter J.K., Yeatman M.T., Kaiser C., Gridelli B., Owens I.S.
J. Biol. Chem. 268:23573-23579(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN1 PHE-170 DEL.
[20]"Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases."
Labrune P., Myara A., Hadchouel M., Ronchi F., Bernard O., Trivin F., Roy Chowdhury N., Roy Chowdhury J., Munnich A., Odievre M.
Hum. Genet. 94:693-697(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN1 VAL-292; GLU-308; ARG-357; THR-368; ARG-381; PRO-401 AND GLU-428.
[21]"Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro."
Erps L.T., Ritter J.K., Hersh J.H., Blossom D., Martin N.C., Owens I.S.
J. Clin. Invest. 93:564-570(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN1 GLU-308 AND PHE-375, CHARACTERIZATION OF VARIANTS CN1 GLU-308 AND PHE-375.
[22]"Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase."
Seppen J., Bosma P.J., Goldhoorn B.G., Bakker C.T.M., Roy Chowdhury J., Roy Chowdhury N., Jansen P.L.M., Oude Elferink R.P.J.
J. Clin. Invest. 94:2385-2391(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN1 PHE-170 DEL; ARG-177; ARG-276 AND PHE-375, VARIANTS CN2 GLN-175 AND TRP-209.
[23]"Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome."
Aono S., Adachi Y., Uyama E., Yamada Y., Keino H., Nanno T., Koiwai O., Sato H.
Lancet 345:958-959(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GILBS ARG-71; GLN-229 AND GLY-367.
Tissue: Liver and Peripheral blood leukocyte.
[24]"A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II."
Seppen J., Steenken E., Lindhout D., Bosma P.J., Oude Elferink R.P.J.
FEBS Lett. 390:294-298(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 ARG-15, CHARACTERIZATION OF VARIANT CN2 ARG-15.
[25]"Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease."
Ciotti M., Chen F., Rubaltelli F.F., Owens I.S.
Biochim. Biophys. Acta 1407:40-50(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 THR-294, CHARACTERIZATION OF VARIANT CN2 THR-294.
[26]"Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II."
Yamamoto K., Soeda Y., Kamisako T., Hosaka H., Fukano M., Sato H., Fujiyama Y., Dachi Y., Satoh Y., Bamba T.
J. Hum. Genet. 43:111-114(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN2 ARG-71; TRP-209; GLN-229 AND ASP-486.
[27]"Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene."
Maruo Y., Sato H., Yamano T., Doida Y., Shimada M.
J. Pediatr. 132:1045-1047(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GILBS ASP-486.
[28]"Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype."
Kadakol A., Ghosh S.S., Sappal B.S., Sharma G., Chowdhury J.R., Chowdhury N.R.
Hum. Mutat. 16:297-306(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN1 ASP-39; PHE-170 DEL; ARG-177; ARG-276; VAL-291; GLU-308; TRP-336; ARG-357; THR-368; PHE-375; ARG-381; SER-387; PRO-401 AND GLU-428, VARIANTS CN2 ARG-15; GLN-175; TRP-209; GLY-225 AND ARG-331, VARIANTS GILBS ARG-71; GLN-229; THR-294; GLY-367 AND ASP-486.
[29]"Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate-glucuronosyltransferase gene."
Maruo Y., Nishizawa K., Sato H., Sawa H., Shimada M.
Pediatrics 106:E59-E59(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HBLRTFN ARG-71 AND ASP-486.
[30]"Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus."
Kadakol A., Sappal B.S., Ghosh S.S., Lowenheim M., Chowdhury A., Chowdhury S., Santra A., Arias I.M., Chowdhury J.R., Chowdhury N.R.
J. Med. Genet. 38:244-249(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 GLN-175.
[31]"Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome."
Labrune P., Myara A., Chalas J., Le Bihan B., Capel L., Francoual J.
Hum. Mutat. 20:399-401(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 ASP-400.
[32]"Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome."
Sutomo R., Laosombat V., Sadewa A.H., Yokoyama N., Nakamura H., Matsuo M., Nishio H.
Pediatr. Int. 44:427-432(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GILBS LEU-83.
[33]"Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II."
Ohnishi A., Emi Y.
Biochem. Biophys. Res. Commun. 310:735-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CN2 ARG-15.
[34]"Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation."
Servedio V., d'Apolito M., Maiorano N., Minuti B., Torricelli F., Ronchi F., Zancan L., Perrotta S., Vajro P., Boschetto L., Iolascon A.
Hum. Mutat. 25:325-325(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN1 GLN-336; ARG-357; PHE-375; SER-387 AND VAL-395, VARIANTS CN2 GLN-34; PHE-170 DEL; TRP-209; GLY-225; LEU-336; TRP-336; ARG-354; CYS-403 AND ASP-478, VARIANTS CN1/CN2 VAL-377 AND ARG-461.
[35]"Seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia."
D'Apolito M., Marrone A., Servedio V., Vajro P., De Falco L., Iolascon A.
Haematologica 92:133-134(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN1 PHE-171 DEL, VARIANTS CN2 TYR-279; ARG-354; VAL-370; VAL-395; PRO-443 AND ARG-461.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Glucuronosyltransferase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M57899 mRNA. Translation: AAA63195.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
M84125 Genomic DNA. Translation: AAA61248.1.
DQ364247 mRNA. Translation: ABC96771.1.
AF297093 Genomic DNA. Translation: AAG30424.1.
AC006985 Genomic DNA. Translation: AAF03522.2. Sequence problems.
D87674 Genomic DNA. Translation: BAA25600.1.
PIRA39092.
RefSeqNP_000454.1. NM_000463.2.
UniGeneHs.554822.

3D structure databases

ProteinModelPortalP22309.
SMRP22309. Positions 116-444.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120087. 4 interactions.
IntActP22309. 2 interactions.
STRING9606.ENSP00000304845.

Chemistry

BindingDBP22309.
ChEMBLCHEMBL1287617.
DrugBankDB01048. Abacavir.
DB00173. Adenine.
DB00586. Diclofenac.
DB00783. Estradiol.
DB00973. Ezetimibe.
DB00762. Irinotecan.
DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00818. Propofol.
DB01045. Rifampin.
DB00197. Troglitazone.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteP22309.

Polymorphism databases

DMDM136729.

Proteomic databases

PaxDbP22309.
PeptideAtlasP22309.
PRIDEP22309.

Protocols and materials databases

DNASU54658.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000608383; ENSP00000476741; ENSG00000241635. [P22309-1]
GeneID54658.
KEGGhsa:54658.
UCSCuc002vvb.3. human. [P22309-1]

Organism-specific databases

CTD54658.
GeneCardsGC02P234668.
HGNCHGNC:12530. UGT1A1.
MIM143500. phenotype.
191740. gene.
218800. phenotype.
237900. phenotype.
601816. phenotype.
606785. phenotype.
neXtProtNX_P22309.
Orphanet79234. Crigler-Najjar syndrome type 1.
79235. Crigler-Najjar syndrome type 2.
357. Gilbert syndrome.
240885. Irinotecan toxicity.
240905. Raltegravir toxicity.
240973. Susceptibility to adverse reaction due to irinotecan treatment.
241017. Susceptibility to icterus due to raltegravir treatment.
2312. Transient familial neonatal hyperbilirubinemia.
PharmGKBPA420.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1819.
HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMAESHFRRM.
OrthoDBEOG7GBFWS.
PhylomeDBP22309.
TreeFamTF315472.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKP22309.

Gene expression databases

BgeeP22309.
CleanExHS_UGT1A1.
GenevestigatorP22309.

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

GenomeRNAi54658.
NextBio57188.
PROP22309.
SOURCESearch...

Entry information

Entry nameUD11_HUMAN
AccessionPrimary (citable) accession number: P22309
Secondary accession number(s): A6NJC3, B8K286
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 158 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