Document Detail


Thirteen UDPglucuronosyltransferase genes are encoded at the human UGT1 gene complex locus.
MedLine Citation:
PMID:  11434514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Q H Gong; J W Cho; T Huang; C Potter; N Gholami; N K Basu; S Kubota; S Carvalho; M W Pennington; I S Owens; N C Popescu
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Pharmacogenetics     Volume:  11     ISSN:  0960-314X     ISO Abbreviation:  Pharmacogenetics     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-07-03     Completed Date:  2001-12-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9211735     Medline TA:  Pharmacogenetics     Country:  England    
Other Details:
Languages:  eng     Pagination:  357-68     Citation Subset:  IM    
Affiliation:
Heritable Disorders Branch, National Institute of Child Health and Hunan Development, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Chromosomes, Artificial, Bacterial
Cloning, Molecular
Cosmids
DNA Primers / genetics
Exons
Gene Library
Glucuronosyltransferase / genetics*
Humans
Isoenzymes / genetics
Liver / enzymology
Molecular Sequence Data
Multigene Family*
Pseudogenes
RNA Caps / genetics
RNA Splicing
RNA, Messenger / genetics
Sequence Deletion
Sequence Homology, Nucleic Acid
TATA Box
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Isoenzymes; 0/RNA Caps; 0/RNA, Messenger; EC 2.4.1.17/Glucuronosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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