Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Denver, Tokyo, and Salt Lake City investigators recently published different complimentary deoxyribonucleic acid (cDNA) sequences for human liver xanthine dehydrogenase/xanthine oxidase (XD/XO). The gene encoding the Denver cDNA was subsequently linked to juvenile familial amyotrophic lateral sclerosis (JFALS) at chromosome 2q33 and has been proposed as the ALS2 locus. The present investigation was undertaken to elucidate the differences between the three cDNA sequences, and we provide evidence that the Denver cDNA encodes aldehyde oxidase (AO): first, the Denver cDNA sequence diverged significantly from the Tokyo and Salt Lake City cDNA sequences which were very similar; second, the deduced protein sequence from the Denver cDNA was very similar to the amino acid sequence of purified rabbit liver AO protein; third, the deduced Denver protein sequence was 76% identical to the encoded 101 amino acid long peptides from partial cDNAs for rabbit and rat AO and 81.7% identical to 300 amino acids from an incomplete cDNA encoding bovine AO; fourth, the Denver gene was expressed in liver, kidney, lung, pancreas, prostate, testes, and ovary while the Tokyo XD gene was expressed predominantly in liver and small intestine; fifth, the Denver gene was previously mapped to chromosome 2q33 which is syntenic to the mouse AO locus on chromosome 1. Our results have revealed dramatic similarities in protein and DNA sequence in the human molybdenum hydroxylases, have uncovered unanticipated complexity in the human molybdenum hydroxylase genes, and advance the potential for AO derived oxygen radicals in JFALS and other human diseases.
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PMID:Identification of the candidate ALS2 gene at chromosome 2q33 as a human aldehyde oxidase gene. 2740 28

Aldehyde oxidase (AOX) is a member of the xanthine oxidase (XO) family of molybdenum hydroxylase, iron-sulfur flavoproteins and is involved in the metabolism of a wide range of native and xenobiotic compounds. The potentially toxic reduced oxygen intermediates (ROI), hydrogen peroxide (H2O2) and superoxide anion (O2(.-)), are generated when reduced AOX becomes oxidized by molecular oxygen, raising the possibility for involvement of AOX in pathophysiology. Indeed, ROI generation by AOX has been directly implicated in hepatic ethanol toxicity. A cDNA encoding human AOX has been cloned, sequenced, and identified as AOX1. AOX1 was proposed as a candidate for an autosomal recessive form of amyotrophic lateral sclerosis (ALS2) because a YAC carrying AOX1 was mapped to the ALS2 locus and was expressed in microglial cells of the spinal cord. As a source of H2O2, AOX could mediate motor neuron degeneration. To provide a basis for further analysis of AOX1 in pathophysiology, and to examine the relationship of the human AOX1 gene to the gene for human xanthine dehydrogenase (XDH), we have studied the chromosomal locus encoding AOX1 in humans. In the present communication, we have analyzed P1 artificial chromosomes containing AOX1. Our refined chromosomal mapping by FISH locates AOX1 very centromere proximal in the 2q33 region at 2q32.3-2q33.1. We present the first complete structural map of an AOX gene and provide direct evidence that human XDH and AOX1 are related by a gene duplication event. In addition, 1500 bp of upstream DNA containing the putative AOX1 promoter were sequenced and expressed. In contrast to the amino acid coding regions, AOX1 and XDH promoter sequences exhibit marked divergence that reflects the differential activation of these closely related genes. Evidence is presented that AOX may be polygenic in humans as it is in plants, Dipterans, and mice.
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PMID:Molecular cloning, refined chromosomal mapping and structural analysis of the human gene encoding aldehyde oxidase (AOX1), a candidate for the ALS2 gene. 2740 59