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MGP005313

UniProt Annotations

Entry Information
Gene NameUDP glucuronosyltransferase 1 family, polypeptide A4
Protein EntryUD14_HUMAN
UniProt IDP22310
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=i1; IsoId=P22310-1; Sequence=Displayed; Name=2; Synonyms=i2, UGT1A4s; IsoId=P22310-2; Sequence=VSP_053960;
Catalytic ActivityUDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.
DiseaseCrigler-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. {ECO:0000269|PubMed:1634050}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseCrigler-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. {ECO:0000269|PubMed:8276413, ECO:0000269|PubMed:8280139}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseGilbert 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.
FunctionUDPGT 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). {ECO:0000250}.
InductionBy phenobarbital.
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.
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 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. {ECO:0000269|PubMed:20610558}.
Tissue SpecificityIsoform 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. {ECO:0000269|PubMed:1339448, ECO:0000269|PubMed:18004212}.
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