MGP Database

MGP005308

UniProt Annotations

Entry Information
Gene NameUDP glucuronosyltransferase 1 family, polypeptide A6
Protein Entry
UniProt IDQ5DT01
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=i1; IsoId=P19224-1; Sequence=Displayed; Name=2; IsoId=P19224-2; Sequence=VSP_045779; Note=No experimental confirmation available.; Name=3; Synonyms=i2, UGT1A6s; IsoId=P19224-3; Sequence=VSP_053962;
Catalytic ActivityUDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.
FunctionUDPGT 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). {ECO:0000250}.
MiscellaneousThe 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.
PolymorphismPolymorphisms 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.
Sequence CautionSequence=BM924331; Type=Erroneous termination; Positions=420; Note=Translated as Glu.; Evidence={ECO:0000305}; Sequence=BM924331; Type=Frameshift; Positions=451, 463; Evidence={ECO:0000305}; Sequence=BM924331; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
SimilarityBelongs to the UDP-glycosyltransferase family. {ECO:0000305}.
Subcellular LocationMicrosome. Endoplasmic reticulum membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
SubunitIsoform 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. {ECO:0000269|PubMed:20610558}.
Tissue SpecificityExpressed 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. {ECO:0000269|PubMed:1339448, ECO:0000269|PubMed:18004212}.
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