Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human alcohol dehydrogenase 5 gene (ADH5) differs from all other human alcohol dehydrogenase genes in its ubiquitous expression, although there are tissue-specific differences in the level of expression. To understand the expression of ADH5, we characterized the structure and function of its 5' region by DNase I foot-printing and transient transfection assays. The region from base pair (bp) -34 to +61, flanking the major transcription start site, had strong promoter activity in three different cell lines: HeLa, H4IIE-C3, and CV-1, and could explain the ubiquitous expression. Two Sp1 sites within that region are footprinted by nuclear extracts from all tissues and cells tested. There are sites further upstream that show cell- and tissue-specific differences in both their patterns of occupancy and their effects on promoter activity. The region between bp -34 and -64 strongly increases promoter activity in H4IIE-C3 cells, weakly activates in CV-1 cells, but has no effect in HeLa cells. The region between bp -127 and -163 is a positive element in both HeLa cells and CV-1 cells, but is a negative regulatory element in H4IIE-C3 cells. These differences in part explain the levels of expression of ADH5 in various tissues. Two regions (bp -64 to -127 and bp -163 to -365) contain negative regulatory elements that reduce promoter activity in all three cells. The 5'-nontranslated region of ADH5 contains two upstream ATGs. Insertion of 12 bp within the putative coding region of these upstream ATGs led to a 1.6-2.3-fold increase in activity. This suggests that the 5'-nontranslated region has regulatory significance.
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PMID:Cell-specific function of cis-acting elements in the regulation of human alcohol dehydrogenase 5 gene expression and effect of the 5'-nontranslated region. 772 11

Alcohol dehydrogenase 5 (ADH5) is a member of the mammalian alcohol dehydrogenase family of yet undefined functions. ADH5 was first identified at the DNA level in human and deer mouse. A rat alcohol dehydrogenase structure of similar type has been isolated at the cDNA level using human ADH5 as a screening probe, where the rat cDNA structure displayed several atypical properties. mRNA for rat ADH5 was found in multiple tissues, especially in the kidney. In vitro translation experiments indicated that rat ADH5 is expressed as efficiently as ADH1 and furthermore, rat ADH5 was readily expressed in COS cells fused to Green Fluorescent Protein. However, no soluble ADH5 protein could be heterologously expressed in Escherichia coli cells with expression systems successfully used for other mammalian ADHs, including fused to glutathione-S-transferase. Molecular modelling of the enzyme indicated that the protein does not fold in a productive way, which can be the explanation why no stable and active ADH5 has been isolated. These results indicate that ADH5, while readily expressed at the mRNA level, does not behave similarly to other mammalian ADHs investigated. The results, in vitro and in silico, suggest an unstable ADH5 structure, which can explain for why no active and stable protein can be isolated. Further possibilities are conceivable: the ADH5 protein may have to interact with a stabiliser, or the gene is actually a pseudogene.
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PMID:Analysis of mammalian alcohol dehydrogenase 5 (ADH5): characterisation of rat ADH5 with comparisons to the corresponding human variant. 2315 88