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Protein

UDP-glucuronosyltransferase 1-6

Gene

UGT1A6

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 has specificity for phenols. Isoform 3 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

  • cellular glucuronidation Source: UniProtKB
  • flavonoid biosynthetic process Source: GO_Central
  • flavonoid glucuronidation Source: GO_Central
  • 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
  • xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
SABIO-RKP19224.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-6 (EC:2.4.1.17)
Short name:
UDPGT 1-6
Short name:
UGT1*6
Short name:
UGT1-06
Short name:
UGT1.6
Alternative name(s):
Phenol-metabolizing UDP-glucuronosyltransferase
UDP-glucuronosyltransferase 1-F
Short name:
UGT-1F
Short name:
UGT1F
UDP-glucuronosyltransferase 1A6
Gene namesi
Name:UGT1A6
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:12538. UGT1A6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei490 – 506HelicalSequence analysisAdd BLAST17

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi54578.
OpenTargetsiENSG00000167165.
PharmGKBiPA37181.

Chemistry databases

ChEMBLiCHEMBL1743316.
DrugBankiDB00316. Acetaminophen.
DB08826. Deferiprone.
DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00818. Propofol.
DB00313. Valproic Acid.

Polymorphism and mutation databases

BioMutaiUGT1A6.
DMDMi29840832.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003600527 – 532UDP-glucuronosyltransferase 1-6Add BLAST506

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi294N-linked (GlcNAc...)Sequence analysis1
Glycosylationi346N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP19224.
PeptideAtlasiP19224.
PRIDEiP19224.

PTM databases

iPTMnetiP19224.
PhosphoSitePlusiP19224.

Expressioni

Tissue specificityi

Expressed in skin. Isoforms 1 and 3 are expressed in kidney and liver. Isoform 1 but not isoform 2 is expressed in colon, esophagus and small intestine.2 Publications

Gene expression databases

BgeeiENSG00000167165.
ExpressionAtlasiP19224. baseline and differential.
GenevisibleiP19224. HS.

Organism-specific databases

HPAiCAB009819.
HPA054065.

Interactioni

Subunit structurei

Isoform 1 interacts with isoform 3/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 3. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, 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

IntActiP19224. 7 interactors.
STRINGi9606.ENSP00000303174.

Chemistry databases

BindingDBiP19224.

Structurei

3D structure databases

ProteinModelPortaliP19224.
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.
InParanoidiP19224.
KOiK00699.
OMAiMIVIDMY.
OrthoDBiEOG091G06JC.
PhylomeDBiP19224.
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 (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19224-1) [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
MACLLRSFQR ISAGVFFLAL WGMVVGDKLL VVPQDGSHWL SMKDIVEVLS
60 70 80 90 100
DRGHEIVVVV PEVNLLLKES KYYTRKIYPV PYDQEELKNR YQSFGNNHFA
110 120 130 140 150
ERSFLTAPQT EYRNNMIVIG LYFINCQSLL QDRDTLNFFK ESKFDALFTD
160 170 180 190 200
PALPCGVILA EYLGLPSVYL FRGFPCSLEH TFSRSPDPVS YIPRCYTKFS
210 220 230 240 250
DHMTFSQRVA NFLVNLLEPY LFYCLFSKYE ELASAVLKRD VDIITLYQKV
260 270 280 290 300
SVWLLRYDFV LEYPRPVMPN MVFIGGINCK KRKDLSQEFE AYINASGEHG
310 320 330 340 350
IVVFSLGSMV SEIPEKKAMA IADALGKIPQ TVLWRYTGTR PSNLANNTIL
360 370 380 390 400
VKWLPQNDLL GHPMTRAFIT HAGSHGVYES ICNGVPMVMM PLFGDQMDNA
410 420 430 440 450
KRMETKGAGV TLNVLEMTSE DLENALKAVI NDKSYKENIM RLSSLHKDRP
460 470 480 490 500
VEPLDLAVFW VEFVMRHKGA PHLRPAAHDL TWYQYHSLDV IGFLLAVVLT
510 520 530
VAFITFKCCA YGYRKCLGKK GRVKKAHKSK TH
Length:532
Mass (Da):60,751
Last modified:April 11, 2003 - v2
Checksum:i4A9EA6A88CBC3136
GO
Isoform 2 (identifier: P19224-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-267: Missing.

Note: No experimental confirmation available.
Show »
Length:265
Mass (Da):29,647
Checksum:iC0DEE8F8EC498CFD
GO
Isoform 3 (identifier: P19224-3) [UniParc]FASTAAdd to basket
Also known as: i2, UGT1A6s

The sequence of this isoform differs from the canonical sequence as follows:
     434-532: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

Show »
Length:443
Mass (Da):50,528
Checksum:iD49A8F5D16A09EDD
GO

Sequence cautioni

The sequence BM924331 differs from that shown. Probable cloning artifact.Curated
The sequence BM924331 differs from that shown. Reason: Frameshift at positions 451 and 463.Curated
The sequence BM924331 differs from that shown. Reason: Erroneous termination at position 420. Translated as Glu.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti231E → K in AAA61251 (PubMed:1339448).Curated1
Sequence conflicti247 – 249YQK → SE in AAA61251 (PubMed:1339448).Curated3
Sequence conflicti328I → N in AAA61251 (PubMed:1339448).Curated1
Sequence conflicti419S → F in BM924331 (PubMed:15489334).Curated1
Sequence conflicti446H → S in BM924331 (PubMed:15489334).Curated1
Sequence conflicti468K → Q in BM924331 (PubMed:15489334).Curated1
Sequence conflicti476 – 477AA → GS in BM924331 (PubMed:15489334).Curated2
Sequence conflicti514R → P in AAA61251 (PubMed:1339448).Curated1

Polymorphismi

Polymorphisms in the UGT1A6 gene define four common haplotypes: UGT1A6*1, UGT1A6*2, UGT1A6*3 and UGT1A6*4. Liver tissue samples that were homozygous for UGT1A6*2 exhibited a high rate of glucuronidation relative to tissues with other genotypes. Biochemical kinetic studies indicate that the UGT1A6*2 allozyme, expressed homozygously, had almost two-fold greater activity toward p-nitrophenol than UGT1A6*1 and when expressed heterozygously (UGT1A6*1/*2) it is associated with low enzyme activity. Common genetic variation in UGT1A6 confers functionally significant differences in biochemical phenotype. This genetic variation might impact clinical efficacy or toxicity of drugs metabolized by UGT1A6.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0246857S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. 1 PublicationCorresponds to variant rs6759892dbSNPEnsembl.1
Natural variantiVAR_02662870S → Y.1 PublicationCorresponds to variant rs1042708dbSNPEnsembl.1
Natural variantiVAR_014784181T → A in allele UGT1A6*2. 4 PublicationsCorresponds to variant rs2070959dbSNPEnsembl.1
Natural variantiVAR_015559184R → S in allele UGT1A6*2 and allele UGT1A6*4. 4 PublicationsCorresponds to variant rs1105879dbSNPEnsembl.1
Natural variantiVAR_026629510A → P.1 PublicationCorresponds to variant rs1042709dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0457791 – 267Missing in isoform 2. 1 PublicationAdd BLAST267
Alternative sequenceiVSP_053962434 – 532SYKEN…KSKTH → RKKQQSGRQM in isoform 3. 1 PublicationAdd BLAST99

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84130 Genomic DNA. Translation: AAC41717.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
J04093 mRNA. Translation: AAA61251.1.
AF297093 Genomic DNA. Translation: AAG30420.1.
DQ364250 mRNA. Translation: ABC96774.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
BM924331 mRNA. No translation available.
AF014112 Genomic DNA. Translation: AAB87411.1.
CCDSiCCDS2507.1. [P19224-1]
CCDS2508.1. [P19224-2]
PIRiA31340.
RefSeqiNP_001063.2. NM_001072.3. [P19224-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000305139; ENSP00000303174; ENSG00000167165. [P19224-1]
ENST00000373424; ENSP00000362523; ENSG00000167165. [P19224-2]
GeneIDi54578.
KEGGihsa:54578.
UCSCiuc002vuu.4. human. [P19224-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84130 Genomic DNA. Translation: AAC41717.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
J04093 mRNA. Translation: AAA61251.1.
AF297093 Genomic DNA. Translation: AAG30420.1.
DQ364250 mRNA. Translation: ABC96774.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
BM924331 mRNA. No translation available.
AF014112 Genomic DNA. Translation: AAB87411.1.
CCDSiCCDS2507.1. [P19224-1]
CCDS2508.1. [P19224-2]
PIRiA31340.
RefSeqiNP_001063.2. NM_001072.3. [P19224-1]
UniGeneiHs.554822.

3D structure databases

ProteinModelPortaliP19224.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP19224. 7 interactors.
STRINGi9606.ENSP00000303174.

Chemistry databases

BindingDBiP19224.
ChEMBLiCHEMBL1743316.
DrugBankiDB00316. Acetaminophen.
DB08826. Deferiprone.
DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.
DB00818. Propofol.
DB00313. Valproic Acid.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

PTM databases

iPTMnetiP19224.
PhosphoSitePlusiP19224.

Polymorphism and mutation databases

BioMutaiUGT1A6.
DMDMi29840832.

Proteomic databases

PaxDbiP19224.
PeptideAtlasiP19224.
PRIDEiP19224.

Protocols and materials databases

DNASUi54578.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305139; ENSP00000303174; ENSG00000167165. [P19224-1]
ENST00000373424; ENSP00000362523; ENSG00000167165. [P19224-2]
GeneIDi54578.
KEGGihsa:54578.
UCSCiuc002vuu.4. human. [P19224-1]

Organism-specific databases

CTDi54578.
DisGeNETi54578.
GeneCardsiUGT1A6.
HGNCiHGNC:12538. UGT1A6.
HPAiCAB009819.
HPA054065.
MIMi191740. gene.
606431. gene.
neXtProtiNX_P19224.
OpenTargetsiENSG00000167165.
PharmGKBiPA37181.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1192. Eukaryota.
COG1819. LUCA.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiP19224.
KOiK00699.
OMAiMIVIDMY.
OrthoDBiEOG091G06JC.
PhylomeDBiP19224.
TreeFamiTF315472.

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
ReactomeiR-HSA-156588. Glucuronidation.
SABIO-RKP19224.

Miscellaneous databases

GeneWikiiUGT1A6.
GenomeRNAii54578.
PROiP19224.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167165.
ExpressionAtlasiP19224. baseline and differential.
GenevisibleiP19224. 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 nameiUD16_HUMAN
AccessioniPrimary (citable) accession number: P19224
Secondary accession number(s): A6NKK6, B8K289, Q96TE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 11, 2003
Last modified: November 2, 2016
This is version 161 of the entry and version 2 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.