Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.

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Gong QH, Cho JW, Huang T, Potter C, Gholami N, Basu NK, Kubota S, Carvalho S, Pennington MW, Owens IS, Popescu NC

Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.

Pharmacogenetics. 2001 Jun;11(4):357-68.

PubMed ID
11434514 [ View in PubMed
]
Abstract

The original novel UGT1 complex locus previously shown to encode six different UDP-glucuronosyltransferase (transferase) genes has been extended and demonstrated to specify a total of 13 isoforms. The genes are designated UGT1A1 through UGT1A13p with four pseudo ones. UGT1A2p and UGT1A11p through UGT1A13p have either nucleotide deletions or flawed TATA boxes and are therefore pseudo. In the 5' region of the locus, the 13 unique exons 1 are arranged in a tandem array with each having its own proximal TATA box element and, in turn, are linked to four common exons to allow for the independent transcriptional initiation to generate overlapping primary transcripts. Only the lead exon in the nine viable primary transcripts is predicted to undergo splicing to the four common exons generating mRNAs with identical 3' ends and transferase isozymes with an identical carboxyl terminus. The unique amino terminus specifies acceptor-substrate selection, and the common carboxyl terminus apparently specifies the interaction with the common donor substrate, UDP-glucuronic acid. In the extended region, the viable TATA boxes are either A(A)TgA(AA)T or AT14AT; in the original locus the element for UGT1A1 is A(TA)7A and TAATT/CAA(A) for all of the other genes. UGT1A1 specifies the critically important bilirubin transferase isoform. The relationships of the exons 1 to each other are as follows: UGT1A2p through UGT1A5 comprises a cluster A that is 87-92% identical, and UGT1A7 through UGT1A13p comprises a cluster B that is 67-91% identical. For the two not included in a cluster, UGT1A1 is more identical to cluster A at 60-63%, whereas UGT1A6 is identical by between 48% and 56% to all other unique exons. The locus was expanded from 95 kb to 218 kb. Extensive probing of clones beyond 218 kb with coding nucleotides for a highly conserved amino acid sequence present in all transferases was unable to detect other exons 1. The mRNAs are differentially expressed in hepatic and extrahepatic tissues. This locus is indeed novel, indicating the least usage of exon sequences in specifying different transferase isozymes that have an expansive substrate range.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
UDP-glucuronosyltransferase 1A9O60656Details
UDP-glucuronosyltransferase 1A1P22309Details
UDP-glucuronosyltransferase 1A4P22310Details
UDP-glucuronosyltransferase 1A3P35503Details
UDP-glucuronosyltransferase 1A10Q9HAW8Details
UDP-glucuronosyltransferase 1A8Q9HAW9Details
UDP-glucuronosyltransferase 1-6P19224Details
UDP-glucuronosyltransferase 1A7Q9HAW7Details