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Protein

UDP-glucuronosyltransferase 1-1

Gene

UGT1A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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 glucuronidates bilirubin 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 1.3 Publications

Catalytic activityi

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.2 Publications

Kineticsi

  1. KM=0.26 µM for bilirubin1 Publication
  1. Vmax=1080 pmol/min/mg enzyme with bilirubin as substrate1 Publication

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • enzyme inhibitor activity Source: BHF-UCL
  • glucuronosyltransferase activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • retinoic acid binding Source: BHF-UCL
  • steroid binding Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: Ensembl
  • animal organ regeneration Source: Ensembl
  • bilirubin conjugation Source: Reactome
  • biphenyl catabolic process Source: Ensembl
  • cellular glucuronidation Source: UniProtKB
  • cellular response to estradiol stimulus Source: Ensembl
  • cellular response to ethanol Source: Ensembl
  • cellular response to glucocorticoid stimulus Source: Ensembl
  • digestion Source: ProtInc
  • drug metabolic process Source: BHF-UCL
  • estrogen metabolic process Source: ProtInc
  • flavone metabolic process Source: BHF-UCL
  • flavonoid biosynthetic process Source: GO_Central
  • flavonoid glucuronidation Source: BHF-UCL
  • heme catabolic process Source: Reactome
  • heterocycle metabolic process Source: BHF-UCL
  • liver development Source: Ensembl
  • negative regulation of cellular glucuronidation Source: UniProtKB
  • negative regulation of fatty acid metabolic process Source: BHF-UCL
  • negative regulation of glucuronosyltransferase activity Source: BHF-UCL
  • negative regulation of steroid metabolic process Source: BHF-UCL
  • response to drug Source: Ensembl
  • response to lipopolysaccharide Source: Ensembl
  • response to nutrient Source: Ensembl
  • response to starvation Source: Ensembl
  • retinoic acid metabolic process Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • xenobiotic glucuronidation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
2.4.1.95. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
R-HSA-189483. Heme degradation.
SABIO-RKP22309.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-1 (EC:2.4.1.17)
Short name:
UDPGT 1-1
Short name:
UGT1*1
Short name:
UGT1-01
Short name:
UGT1.1
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 namesi
Name:UGT1A1
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:12530. UGT1A1.

Subcellular locationi

Isoform 1 :
Isoform 2 :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei491 – 507HelicalSequence analysisAdd BLAST17

GO - Cellular componenti

  • cytochrome complex Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum chaperone complex Source: Ensembl
  • endoplasmic reticulum membrane Source: BHF-UCL
  • integral component of plasma membrane Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Gilbert syndrome (GILBS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionOccurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
See also OMIM:143500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00950471G → 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. 7 PublicationsCorresponds to variant rs4148323dbSNPEnsembl.1
Natural variantiVAR_02613683F → L in GILBS; displays less than 10% of wild-type bilirubin glucuronidation activity. 2 PublicationsCorresponds to variant rs56059937dbSNPEnsembl.1
Natural variantiVAR_009505229P → Q in CN2 and GILBS; displays 2-fold decrease in biluribin affinity and 61% of wild-type bilirubin glucuronidation activity. 4 PublicationsCorresponds to variant rs35350960dbSNPEnsembl.1
Natural variantiVAR_026139294I → T in GILBS and CN2; 40-55% normal activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype. 2 PublicationsCorresponds to variant rs72551347dbSNPEnsembl.1
Natural variantiVAR_012283367R → G in GILBS. 2 PublicationsCorresponds to variant rs55750087dbSNPEnsembl.1
Natural variantiVAR_007709486Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. 7 PublicationsCorresponds to variant rs34993780dbSNPEnsembl.1
Transient familial neonatal hyperbilirubinemia (HBLRTFN)1 Publication
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.
Disease descriptionA 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.
See also OMIM:237900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00950471G → 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. 7 PublicationsCorresponds to variant rs4148323dbSNPEnsembl.1
Natural variantiVAR_007709486Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. 7 PublicationsCorresponds to variant rs34993780dbSNPEnsembl.1
Crigler-Najjar syndrome 1 (CN1)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients 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.
See also OMIM:218800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07140236D → N in CN1. 1 Publication1
Natural variantiVAR_02613539H → D in CN1. 1 PublicationCorresponds to variant rs72551339dbSNPEnsembl.1
Natural variantiVAR_007695170Missing in CN1 and CN2; has nearly normal activity at pH 7.6 and is inactive at pH 6.4. 5 Publications1
Natural variantiVAR_007697177C → R in CN1. 2 PublicationsCorresponds to variant rs72551342dbSNPEnsembl.1
Natural variantiVAR_007699276G → R in CN1. 2 PublicationsCorresponds to variant rs72551345dbSNPEnsembl.1
Natural variantiVAR_026138291E → V in CN1. 1 Publication1
Natural variantiVAR_007700292A → V in CN1. 1 Publication1
Natural variantiVAR_007701308G → E in CN1; no enzyme activity. 3 PublicationsCorresponds to variant rs62625011dbSNPEnsembl.1
Natural variantiVAR_026140336R → L in CN1 and CN2. 1 Publication1
Natural variantiVAR_026141336R → Q in CN1. 1 PublicationCorresponds to variant rs750453538dbSNPEnsembl.1
Natural variantiVAR_007703357Q → R in CN1. 3 PublicationsCorresponds to variant rs72551351dbSNPEnsembl.1
Natural variantiVAR_007704368A → T in CN1. 2 PublicationsCorresponds to variant rs72551352dbSNPEnsembl.1
Natural variantiVAR_007705375S → F in CN1; no enzyme activity. 5 PublicationsCorresponds to variant rs72551353dbSNPEnsembl.1
Natural variantiVAR_026144376H → R in CN1 and CN2. 1
Natural variantiVAR_026145377G → V in CN1 and CN2. 1 Publication1
Natural variantiVAR_007706381S → R in CN1. 2 PublicationsCorresponds to variant rs72551354dbSNPEnsembl.1
Natural variantiVAR_026146387P → S in CN1. 2 Publications1
Natural variantiVAR_026147395G → V in CN1; has no residual bilirubin glucuronidation activity. 3 PublicationsCorresponds to variant rs367897068dbSNPEnsembl.1
Natural variantiVAR_007707401A → P in CN1. 2 PublicationsCorresponds to variant rs72551355dbSNPEnsembl.1
Natural variantiVAR_064960402K → T in CN1; has no residual bilirubin glucuronidation activity; N-glycosylation does take place at this new additional site. 1 Publication1
Natural variantiVAR_007708428K → E in CN1. 2 PublicationsCorresponds to variant rs72551356dbSNPEnsembl.1
Natural variantiVAR_026149461W → R in CN1 and CN2. 2 Publications1
Crigler-Najjar syndrome 2 (CN2)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients 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.
See also OMIM:606785
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01941015L → R in CN2; mutant protein rapidly degraded by the proteasome owing to its mislocalization in the cell. 4 PublicationsCorresponds to variant rs111033541dbSNPEnsembl.1
Natural variantiVAR_02613434P → Q in CN2. 1 Publication1
Natural variantiVAR_00950471G → 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. 7 PublicationsCorresponds to variant rs4148323dbSNPEnsembl.1
Natural variantiVAR_007695170Missing in CN1 and CN2; has nearly normal activity at pH 7.6 and is inactive at pH 6.4. 5 Publications1
Natural variantiVAR_064955171Missing in CN2. 1 Publication1
Natural variantiVAR_019411175L → Q in CN2; has low residual bilirubin glucuronidation activity of about 4.6% of that of the wild-type protein. 4 PublicationsCorresponds to variant rs72551341dbSNPEnsembl.1
Natural variantiVAR_064956191S → F in CN2; has low residual bilirubin glucuronidation activity of about 5.3% of that of the wild-type protein. 1 Publication1
Natural variantiVAR_007698209R → W in CN2; has low residual bilirubin glucuronidation activity of about 2.9% of that of the wild-type protein. 5 PublicationsCorresponds to variant rs72551343dbSNPEnsembl.1
Natural variantiVAR_026137225V → G in CN2. 2 PublicationsCorresponds to variant rs35003977dbSNPEnsembl.1
Natural variantiVAR_009505229P → Q in CN2 and GILBS; displays 2-fold decrease in biluribin affinity and 61% of wild-type bilirubin glucuronidation activity. 4 PublicationsCorresponds to variant rs35350960dbSNPEnsembl.1
Natural variantiVAR_071403230Y → C in CN2. 1 PublicationCorresponds to variant rs754922685dbSNPEnsembl.1
Natural variantiVAR_064957279N → Y in CN2. 1 PublicationCorresponds to variant rs397978903dbSNPEnsembl.1
Natural variantiVAR_026139294I → T in GILBS and CN2; 40-55% normal activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype. 2 PublicationsCorresponds to variant rs72551347dbSNPEnsembl.1
Natural variantiVAR_007702331Q → R in CN2; has no residual bilirubin glucuronidation activity. 3 PublicationsCorresponds to variant rs72551348dbSNPEnsembl.1
Natural variantiVAR_026140336R → L in CN1 and CN2. 1 Publication1
Natural variantiVAR_026142336R → W in CN2; has very low residual bilirubin glucuronidation activity of about 0.4% of that of the wild-type protein. 3 PublicationsCorresponds to variant rs139607673dbSNPEnsembl.1
Natural variantiVAR_026143354W → R in CN2. 2 Publications1
Natural variantiVAR_071404367R → C in CN2. 1 PublicationCorresponds to variant rs55750087dbSNPEnsembl.1
Natural variantiVAR_064958370I → V in CN2. 1 PublicationCorresponds to variant rs748989741dbSNPEnsembl.1
Natural variantiVAR_026144376H → R in CN1 and CN2. 1
Natural variantiVAR_026145377G → V in CN1 and CN2. 1 Publication1
Natural variantiVAR_064959387P → H in CN2; has no residual bilirubin glucuronidation activity. 1 Publication1
Natural variantiVAR_019412400N → D in CN2. 1 PublicationCorresponds to variant rs28934877dbSNPEnsembl.1
Natural variantiVAR_026148403R → C in CN2. 1 PublicationCorresponds to variant rs778766461dbSNPEnsembl.1
Natural variantiVAR_064961443L → P in CN2; has no residual bilirubin glucuronidation activity. 2 PublicationsCorresponds to variant rs758411577dbSNPEnsembl.1
Natural variantiVAR_026149461W → R in CN1 and CN2. 2 Publications1
Natural variantiVAR_026150478A → D in CN2. 1 Publication1
Natural variantiVAR_007709486Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. 7 PublicationsCorresponds to variant rs34993780dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi54658.
MalaCardsiUGT1A1.
MIMi143500. phenotype.
218800. phenotype.
237900. phenotype.
601816. phenotype.
606785. phenotype.
OpenTargetsiENSG00000241635.
Orphaneti79234. Crigler-Najjar syndrome type 1.
79235. Crigler-Najjar syndrome type 2.
357. Gilbert syndrome.
240885. Irinotecan toxicity.
240905. Raltegravir toxicity.
2312. Transient familial neonatal hyperbilirubinemia.
PharmGKBiPA37181.
PA420.

Chemistry databases

ChEMBLiCHEMBL1287617.
DrugBankiDB01048. Abacavir.
DB00316. Acetaminophen.
DB00173. Adenine.
DB01076. Atorvastatin.
DB06626. Axitinib.
DB00586. Diclofenac.
DB08930. Dolutegravir.
DB06210. Eltrombopag.
DB00530. Erlotinib.
DB00783. Estradiol.
DB00773. Etoposide.
DB00973. Ezetimibe.
DB04953. Ezogabine.
DB01544. Flunitrazepam.
DB00712. Flurbiprofen.
DB01095. Fluvastatin.
DB01050. Ibuprofen.
DB05039. Indacaterol.
DB00328. Indomethacin.
DB00762. Irinotecan.
DB00678. Losartan.
DB00227. Lovastatin.
DB00295. Morphine.
DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00704. Naltrexone.
DB00788. Naproxen.
DB04868. Nilotinib.
DB06589. Pazopanib.
DB00818. Propofol.
DB06817. Raltegravir.
DB08896. Regorafenib.
DB01045. Rifampicin.
DB00641. Simvastatin.
DB00398. Sorafenib.
DB00870. Suprofen.
DB01420. Testosterone Propionate.

Polymorphism and mutation databases

BioMutaiUGT1A1.
DMDMi136729.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000003600026 – 533UDP-glucuronosyltransferase 1-1Add BLAST508

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi102N-linked (GlcNAc...)1 Publication1
Glycosylationi295N-linked (GlcNAc...)Sequence analysis1
Glycosylationi347N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP22309.
PeptideAtlasiP22309.
PRIDEiP22309.

PTM databases

iPTMnetiP22309.
PhosphoSitePlusiP22309.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiENSG00000241635.
CleanExiHS_UGT1A1.
ExpressionAtlasiP22309. baseline and differential.
GenevisibleiP22309. HS.

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 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.2 Publications

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi120087. 3 interactors.
IntActiP22309. 9 interactors.
STRINGi9606.ENSP00000304845.

Chemistry databases

BindingDBiP22309.

Structurei

3D structure databases

ProteinModelPortaliP22309.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the UDP-glycosyltransferase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1192. Eukaryota.
COG1819. LUCA.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiP22309.
KOiK00699.
OMAiLEESHFD.
OrthoDBiEOG091G06JC.
PhylomeDBiP22309.
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. AlignAdd to basket

Isoform 1 (identifier: P22309-1) [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
MAVESQGGRP LVLGLLLCVL GPVVSHAGKI LLIPVDGSHW LSMLGAIQQL
60 70 80 90 100
QQRGHEIVVL APDASLYIRD GAFYTLKTYP VPFQREDVKE SFVSLGHNVF
110 120 130 140 150
ENDSFLQRVI KTYKKIKKDS AMLLSGCSHL LHNKELMASL AESSFDVMLT
160 170 180 190 200
DPFLPCSPIV AQYLSLPTVF FLHALPCSLE FEATQCPNPF SYVPRPLSSH
210 220 230 240 250
SDHMTFLQRV KNMLIAFSQN FLCDVVYSPY ATLASEFLQR EVTVQDLLSS
260 270 280 290 300
ASVWLFRSDF VKDYPRPIMP NMVFVGGINC LHQNPLSQEF EAYINASGEH
310 320 330 340 350
GIVVFSLGSM VSEIPEKKAM AIADALGKIP QTVLWRYTGT RPSNLANNTI
360 370 380 390 400
LVKWLPQNDL LGHPMTRAFI THAGSHGVYE SICNGVPMVM MPLFGDQMDN
410 420 430 440 450
AKRMETKGAG VTLNVLEMTS EDLENALKAV INDKSYKENI MRLSSLHKDR
460 470 480 490 500
PVEPLDLAVF WVEFVMRHKG APHLRPAAHD LTWYQYHSLD VIGFLLAVVL
510 520 530
TVAFITFKCC AYGYRKCLGK KGRVKKAHKS KTH
Length:533
Mass (Da):59,591
Last modified:August 1, 1991 - v1
Checksum:i19C90231AD0EB547
GO
Isoform 2 (identifier: P22309-2) [UniParc]FASTAAdd to basket
Also known as: i2, UGT1A1s

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

Show »
Length:444
Mass (Da):49,368
Checksum:i71E6711DDEFED403
GO

Sequence cautioni

The sequence AAA61247 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAF03522 differs from that shown. Reason: Erroneous gene model prediction.Curated

Polymorphismi

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01941015L → R in CN2; mutant protein rapidly degraded by the proteasome owing to its mislocalization in the cell. 4 PublicationsCorresponds to variant rs111033541dbSNPEnsembl.1
Natural variantiVAR_02613434P → Q in CN2. 1 Publication1
Natural variantiVAR_07140236D → N in CN1. 1 Publication1
Natural variantiVAR_02613539H → D in CN1. 1 PublicationCorresponds to variant rs72551339dbSNPEnsembl.1
Natural variantiVAR_00950471G → 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. 7 PublicationsCorresponds to variant rs4148323dbSNPEnsembl.1
Natural variantiVAR_02613683F → L in GILBS; displays less than 10% of wild-type bilirubin glucuronidation activity. 2 PublicationsCorresponds to variant rs56059937dbSNPEnsembl.1
Natural variantiVAR_007695170Missing in CN1 and CN2; has nearly normal activity at pH 7.6 and is inactive at pH 6.4. 5 Publications1
Natural variantiVAR_064955171Missing in CN2. 1 Publication1
Natural variantiVAR_019411175L → Q in CN2; has low residual bilirubin glucuronidation activity of about 4.6% of that of the wild-type protein. 4 PublicationsCorresponds to variant rs72551341dbSNPEnsembl.1
Natural variantiVAR_007697177C → R in CN1. 2 PublicationsCorresponds to variant rs72551342dbSNPEnsembl.1
Natural variantiVAR_064956191S → F in CN2; has low residual bilirubin glucuronidation activity of about 5.3% of that of the wild-type protein. 1 Publication1
Natural variantiVAR_007698209R → W in CN2; has low residual bilirubin glucuronidation activity of about 2.9% of that of the wild-type protein. 5 PublicationsCorresponds to variant rs72551343dbSNPEnsembl.1
Natural variantiVAR_026137225V → G in CN2. 2 PublicationsCorresponds to variant rs35003977dbSNPEnsembl.1
Natural variantiVAR_009505229P → Q in CN2 and GILBS; displays 2-fold decrease in biluribin affinity and 61% of wild-type bilirubin glucuronidation activity. 4 PublicationsCorresponds to variant rs35350960dbSNPEnsembl.1
Natural variantiVAR_071403230Y → C in CN2. 1 PublicationCorresponds to variant rs754922685dbSNPEnsembl.1
Natural variantiVAR_007699276G → R in CN1. 2 PublicationsCorresponds to variant rs72551345dbSNPEnsembl.1
Natural variantiVAR_064957279N → Y in CN2. 1 PublicationCorresponds to variant rs397978903dbSNPEnsembl.1
Natural variantiVAR_026138291E → V in CN1. 1 Publication1
Natural variantiVAR_007700292A → V in CN1. 1 Publication1
Natural variantiVAR_026139294I → T in GILBS and CN2; 40-55% normal activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype. 2 PublicationsCorresponds to variant rs72551347dbSNPEnsembl.1
Natural variantiVAR_007701308G → E in CN1; no enzyme activity. 3 PublicationsCorresponds to variant rs62625011dbSNPEnsembl.1
Natural variantiVAR_007702331Q → R in CN2; has no residual bilirubin glucuronidation activity. 3 PublicationsCorresponds to variant rs72551348dbSNPEnsembl.1
Natural variantiVAR_026140336R → L in CN1 and CN2. 1 Publication1
Natural variantiVAR_026141336R → Q in CN1. 1 PublicationCorresponds to variant rs750453538dbSNPEnsembl.1
Natural variantiVAR_026142336R → W in CN2; has very low residual bilirubin glucuronidation activity of about 0.4% of that of the wild-type protein. 3 PublicationsCorresponds to variant rs139607673dbSNPEnsembl.1
Natural variantiVAR_026143354W → R in CN2. 2 Publications1
Natural variantiVAR_007703357Q → R in CN1. 3 PublicationsCorresponds to variant rs72551351dbSNPEnsembl.1
Natural variantiVAR_071404367R → C in CN2. 1 PublicationCorresponds to variant rs55750087dbSNPEnsembl.1
Natural variantiVAR_012283367R → G in GILBS. 2 PublicationsCorresponds to variant rs55750087dbSNPEnsembl.1
Natural variantiVAR_007704368A → T in CN1. 2 PublicationsCorresponds to variant rs72551352dbSNPEnsembl.1
Natural variantiVAR_064958370I → V in CN2. 1 PublicationCorresponds to variant rs748989741dbSNPEnsembl.1
Natural variantiVAR_007705375S → F in CN1; no enzyme activity. 5 PublicationsCorresponds to variant rs72551353dbSNPEnsembl.1
Natural variantiVAR_026144376H → R in CN1 and CN2. 1
Natural variantiVAR_026145377G → V in CN1 and CN2. 1 Publication1
Natural variantiVAR_007706381S → R in CN1. 2 PublicationsCorresponds to variant rs72551354dbSNPEnsembl.1
Natural variantiVAR_064959387P → H in CN2; has no residual bilirubin glucuronidation activity. 1 Publication1
Natural variantiVAR_026146387P → S in CN1. 2 Publications1
Natural variantiVAR_026147395G → V in CN1; has no residual bilirubin glucuronidation activity. 3 PublicationsCorresponds to variant rs367897068dbSNPEnsembl.1
Natural variantiVAR_019412400N → D in CN2. 1 PublicationCorresponds to variant rs28934877dbSNPEnsembl.1
Natural variantiVAR_007707401A → P in CN1. 2 PublicationsCorresponds to variant rs72551355dbSNPEnsembl.1
Natural variantiVAR_064960402K → T in CN1; has no residual bilirubin glucuronidation activity; N-glycosylation does take place at this new additional site. 1 Publication1
Natural variantiVAR_026148403R → C in CN2. 1 PublicationCorresponds to variant rs778766461dbSNPEnsembl.1
Natural variantiVAR_007708428K → E in CN1. 2 PublicationsCorresponds to variant rs72551356dbSNPEnsembl.1
Natural variantiVAR_064961443L → P in CN2; has no residual bilirubin glucuronidation activity. 2 PublicationsCorresponds to variant rs758411577dbSNPEnsembl.1
Natural variantiVAR_026149461W → R in CN1 and CN2. 2 Publications1
Natural variantiVAR_026150478A → D in CN2. 1 Publication1
Natural variantiVAR_007709486Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. 7 PublicationsCorresponds to variant rs34993780dbSNPEnsembl.1
Natural variantiVAR_025355511A → P.Corresponds to variant rs1042709dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053958435 – 533SYKEN…KSKTH → RKKQQSGRQM in isoform 2. 1 PublicationAdd BLAST99

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2510.1. [P22309-1]
PIRiA39092.
RefSeqiNP_000454.1. NM_000463.2. [P22309-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000305208; ENSP00000304845; ENSG00000241635. [P22309-1]
ENST00000360418; ENSP00000353593; ENSG00000241635. [P22309-2]
GeneIDi54658.
KEGGihsa:54658.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Glucuronosyltransferase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2510.1. [P22309-1]
PIRiA39092.
RefSeqiNP_000454.1. NM_000463.2. [P22309-1]
UniGeneiHs.554822.

3D structure databases

ProteinModelPortaliP22309.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120087. 3 interactors.
IntActiP22309. 9 interactors.
STRINGi9606.ENSP00000304845.

Chemistry databases

BindingDBiP22309.
ChEMBLiCHEMBL1287617.
DrugBankiDB01048. Abacavir.
DB00316. Acetaminophen.
DB00173. Adenine.
DB01076. Atorvastatin.
DB06626. Axitinib.
DB00586. Diclofenac.
DB08930. Dolutegravir.
DB06210. Eltrombopag.
DB00530. Erlotinib.
DB00783. Estradiol.
DB00773. Etoposide.
DB00973. Ezetimibe.
DB04953. Ezogabine.
DB01544. Flunitrazepam.
DB00712. Flurbiprofen.
DB01095. Fluvastatin.
DB01050. Ibuprofen.
DB05039. Indacaterol.
DB00328. Indomethacin.
DB00762. Irinotecan.
DB00678. Losartan.
DB00227. Lovastatin.
DB00295. Morphine.
DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00704. Naltrexone.
DB00788. Naproxen.
DB04868. Nilotinib.
DB06589. Pazopanib.
DB00818. Propofol.
DB06817. Raltegravir.
DB08896. Regorafenib.
DB01045. Rifampicin.
DB00641. Simvastatin.
DB00398. Sorafenib.
DB00870. Suprofen.
DB01420. Testosterone Propionate.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

PTM databases

iPTMnetiP22309.
PhosphoSitePlusiP22309.

Polymorphism and mutation databases

BioMutaiUGT1A1.
DMDMi136729.

Proteomic databases

PaxDbiP22309.
PeptideAtlasiP22309.
PRIDEiP22309.

Protocols and materials databases

DNASUi54658.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305208; ENSP00000304845; ENSG00000241635. [P22309-1]
ENST00000360418; ENSP00000353593; ENSG00000241635. [P22309-2]
GeneIDi54658.
KEGGihsa:54658.

Organism-specific databases

CTDi54658.
DisGeNETi54658.
GeneCardsiUGT1A1.
HGNCiHGNC:12530. UGT1A1.
MalaCardsiUGT1A1.
MIMi143500. phenotype.
191740. gene.
218800. phenotype.
237900. phenotype.
601816. phenotype.
606785. phenotype.
neXtProtiNX_P22309.
OpenTargetsiENSG00000241635.
Orphaneti79234. Crigler-Najjar syndrome type 1.
79235. Crigler-Najjar syndrome type 2.
357. Gilbert syndrome.
240885. Irinotecan toxicity.
240905. Raltegravir toxicity.
2312. Transient familial neonatal hyperbilirubinemia.
PharmGKBiPA37181.
PA420.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1192. Eukaryota.
COG1819. LUCA.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiP22309.
KOiK00699.
OMAiLEESHFD.
OrthoDBiEOG091G06JC.
PhylomeDBiP22309.
TreeFamiTF315472.

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
2.4.1.95. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
R-HSA-189483. Heme degradation.
SABIO-RKP22309.

Miscellaneous databases

GenomeRNAii54658.
PROiP22309.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000241635.
CleanExiHS_UGT1A1.
ExpressionAtlasiP22309. baseline and differential.
GenevisibleiP22309. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiUD11_HUMAN
AccessioniPrimary (citable) accession number: P22309
Secondary accession number(s): A6NJC3, B8K286
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 30, 2016
This is version 185 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.