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Protein

UDP-glucuronosyltransferase 1-4

Gene

UGT1A4

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. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 (By similarity).By similarity

Catalytic activityi

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

GO - Molecular functioni

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

GO - Biological processi

  • bilirubin conjugation Source: Reactome
  • cellular glucuronidation Source: UniProtKB
  • flavonoid biosynthetic process Source: GO_Central
  • flavonoid glucuronidation Source: GO_Central
  • heme catabolic process Source: Reactome
  • negative regulation of cellular glucuronidation Source: BHF-UCL
  • negative regulation of fatty acid metabolic process Source: BHF-UCL
  • negative regulation of glucuronosyltransferase activity Source: BHF-UCL
  • xenobiotic glucuronidation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:HS11970-MONOMER.
ZFISH:HS11970-MONOMER.
BRENDAi2.4.1.17. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
R-HSA-189483. Heme degradation.
SABIO-RKP22310.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-4 (EC:2.4.1.17)
Short name:
UDPGT 1-4
Short name:
UGT1*4
Short name:
UGT1-04
Short name:
UGT1.4
Alternative name(s):
Bilirubin-specific UDPGT isozyme 2
Short name:
hUG-BR2
UDP-glucuronosyltransferase 1-D
Short name:
UGT-1D
Short name:
UGT1D
UDP-glucuronosyltransferase 1A4
Gene namesi
Name:UGT1A4
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:12536. UGT1A4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei492 – 508HelicalSequence analysisAdd BLAST17

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: BHF-UCL
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Involvement in diseasei

Gilbert syndrome (GILBS)1 Publication
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
Crigler-Najjar syndrome 1 (CN1)1 Publication
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_007711376S → F in CN1. 1 PublicationCorresponds to variant rs72551353dbSNPEnsembl.1
Crigler-Najjar syndrome 2 (CN2)2 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_009506132L → P in CN2. 1 PublicationCorresponds to variant rs72551337dbSNPEnsembl.1
Natural variantiVAR_007710332Q → R in CN2. 1 PublicationCorresponds to variant rs72551348dbSNPEnsembl.1
Natural variantiVAR_009507487Y → D in CN2. 1 PublicationCorresponds to variant rs34993780dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi54657.
MalaCardsiUGT1A4.
MIMi143500. phenotype.
218800. phenotype.
606785. phenotype.
OpenTargetsiENSG00000244474.
PharmGKBiPA37179.

Chemistry databases

ChEMBLiCHEMBL3619.
DrugBankiDB06216. Asenapine.
DB00363. Clozapine.
DB04953. Ezogabine.
DB00555. Lamotrigine.
DB00683. Midazolam.
DB00910. Paricalcitol.
DB00675. Tamoxifen.
DB00831. Trifluoperazine.
DB00313. Valproic Acid.

Polymorphism and mutation databases

BioMutaiUGT1A4.
DMDMi136731.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 28Sequence analysisAdd BLAST28
ChainiPRO_000003600329 – 534UDP-glucuronosyltransferase 1-4Add BLAST506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi119N-linked (GlcNAc...)Sequence analysis1
Glycosylationi142N-linked (GlcNAc...)1 Publication1
Glycosylationi296N-linked (GlcNAc...)Sequence analysis1
Glycosylationi348N-linked (GlcNAc...)1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP22310.
PeptideAtlasiP22310.
PRIDEiP22310.

PTM databases

iPTMnetiP22310.
PhosphoSitePlusiP22310.

Expressioni

Tissue specificityi

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

Inductioni

By phenobarbital.

Gene expression databases

BgeeiENSG00000244474.
GenevisibleiP22310. HS.

Organism-specific databases

HPAiCAB033048.

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, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10.1 Publication

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi120086. 1 interactor.
IntActiP22310. 9 interactors.
STRINGi9606.ENSP00000362508.

Chemistry databases

BindingDBiP22310.

Structurei

3D structure databases

ProteinModelPortaliP22310.
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.
InParanoidiP22310.
KOiK00699.
OMAiICHTFSA.
OrthoDBiEOG091G06JC.
PhylomeDBiP22310.
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: P22310-1) [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
MARGLQVPLP RLATGLLLLL SVQPWAESGK VLVVPTDGSP WLSMREALRE
60 70 80 90 100
LHARGHQAVV LTPEVNMHIK EEKFFTLTAY AVPWTQKEFD RVTLGYTQGF
110 120 130 140 150
FETEHLLKRY SRSMAIMNNV SLALHRCCVE LLHNEALIRH LNATSFDVVL
160 170 180 190 200
TDPVNLCGAV LAKYLSIPAV FFWRYIPCDL DFKGTQCPNP SSYIPKLLTT
210 220 230 240 250
NSDHMTFLQR VKNMLYPLAL SYICHTFSAP YASLASELFQ REVSVVDLVS
260 270 280 290 300
YASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANGKPLSQE 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):60,025
Last modified:August 1, 1991 - v1
Checksum:iAB745D46F57538BE
GO
Isoform 2 (identifier: P22310-2) [UniParc]FASTAAdd to basket
Also known as: i2, UGT1A4s

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

Show »
Length:445
Mass (Da):49,802
Checksum:iBB72EF2CDE4C0482
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05984411R → W.Corresponds to variant rs3892221dbSNPEnsembl.1
Natural variantiVAR_02468424P → T.1 PublicationCorresponds to variant rs6755571dbSNPEnsembl.1
Natural variantiVAR_05858448L → V.2 PublicationsCorresponds to variant rs2011425dbSNPEnsembl.1
Natural variantiVAR_06187068H → Y.Corresponds to variant rs45621441dbSNPEnsembl.1
Natural variantiVAR_009506132L → P in CN2. 1 PublicationCorresponds to variant rs72551337dbSNPEnsembl.1
Natural variantiVAR_052454176I → F.Corresponds to variant rs45540231dbSNPEnsembl.1
Natural variantiVAR_007710332Q → R in CN2. 1 PublicationCorresponds to variant rs72551348dbSNPEnsembl.1
Natural variantiVAR_007711376S → F in CN1. 1 PublicationCorresponds to variant rs72551353dbSNPEnsembl.1
Natural variantiVAR_009507487Y → D in CN2. 1 PublicationCorresponds to variant rs34993780dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053960436 – 534SYKEN…KSKTH → RKKQQSGRQM in isoform 2. 2 PublicationsAdd BLAST99

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84128 Genomic DNA. Translation: AAA61249.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
M57951 mRNA. Translation: AAA63196.1.
AF297093 Genomic DNA. Translation: AAG30422.1.
AY435139 mRNA. Translation: AAR95640.1.
AK313623 mRNA. Translation: BAG36384.1.
DQ364249 mRNA. Translation: ABC96773.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71061.1.
BC139784 mRNA. Translation: AAI39785.1.
CCDSiCCDS33405.1. [P22310-1]
RefSeqiNP_009051.1. NM_007120.2. [P22310-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000373409; ENSP00000362508; ENSG00000244474. [P22310-1]
ENST00000450233; ENSP00000408608; ENSG00000244474. [P22310-2]
GeneIDi54657.
KEGGihsa:54657.
UCSCiuc002vux.4. human. [P22310-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84128 Genomic DNA. Translation: AAA61249.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
M57951 mRNA. Translation: AAA63196.1.
AF297093 Genomic DNA. Translation: AAG30422.1.
AY435139 mRNA. Translation: AAR95640.1.
AK313623 mRNA. Translation: BAG36384.1.
DQ364249 mRNA. Translation: ABC96773.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71061.1.
BC139784 mRNA. Translation: AAI39785.1.
CCDSiCCDS33405.1. [P22310-1]
RefSeqiNP_009051.1. NM_007120.2. [P22310-1]
UniGeneiHs.554822.

3D structure databases

ProteinModelPortaliP22310.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120086. 1 interactor.
IntActiP22310. 9 interactors.
STRINGi9606.ENSP00000362508.

Chemistry databases

BindingDBiP22310.
ChEMBLiCHEMBL3619.
DrugBankiDB06216. Asenapine.
DB00363. Clozapine.
DB04953. Ezogabine.
DB00555. Lamotrigine.
DB00683. Midazolam.
DB00910. Paricalcitol.
DB00675. Tamoxifen.
DB00831. Trifluoperazine.
DB00313. Valproic Acid.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

PTM databases

iPTMnetiP22310.
PhosphoSitePlusiP22310.

Polymorphism and mutation databases

BioMutaiUGT1A4.
DMDMi136731.

Proteomic databases

PaxDbiP22310.
PeptideAtlasiP22310.
PRIDEiP22310.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373409; ENSP00000362508; ENSG00000244474. [P22310-1]
ENST00000450233; ENSP00000408608; ENSG00000244474. [P22310-2]
GeneIDi54657.
KEGGihsa:54657.
UCSCiuc002vux.4. human. [P22310-1]

Organism-specific databases

CTDi54657.
DisGeNETi54657.
GeneCardsiUGT1A4.
HGNCiHGNC:12536. UGT1A4.
HPAiCAB033048.
MalaCardsiUGT1A4.
MIMi143500. phenotype.
191740. gene.
218800. phenotype.
606429. gene.
606785. phenotype.
neXtProtiNX_P22310.
OpenTargetsiENSG00000244474.
PharmGKBiPA37179.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1192. Eukaryota.
COG1819. LUCA.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiP22310.
KOiK00699.
OMAiICHTFSA.
OrthoDBiEOG091G06JC.
PhylomeDBiP22310.
TreeFamiTF315472.

Enzyme and pathway databases

BioCyciMetaCyc:HS11970-MONOMER.
ZFISH:HS11970-MONOMER.
BRENDAi2.4.1.17. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
R-HSA-189483. Heme degradation.
SABIO-RKP22310.

Miscellaneous databases

GeneWikiiUGT1A4.
GenomeRNAii54657.
PROiP22310.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000244474.
GenevisibleiP22310. 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 nameiUD14_HUMAN
AccessioniPrimary (citable) accession number: P22310
Secondary accession number(s): B2R937, B8K288, Q5DT00
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: November 30, 2016
This is version 172 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.