Abstract
To search for a mammalian homologue of ATX1, a human liver cDNA library was screened and a cDNA clone was isolated, which encodes a protein with 47% amino acid identity to Atx1p including conservation of the MTCXGC copper-binding domain. RNA blot analysis using this cDNA identified an abundant 0.5-kilobase mRNA in all human tissues and cell lines examined. Southern blot analysis using this same clone indicated that the corresponding gene exists as a single copy in the haploid genome, and chromosomal localization by fluorescence in situ hybridization detected this locus at the interface between bands 5q32 and 5q33. Yeast strains lacking copper/zinc superoxide dismutase (SOD1) are sensitive to redox cycling agents and dioxygen and are auxotrophic for lysine when grown in air, and expression of this human ATX1 homologue (HAH1) in these strains restored growth on lysine-deficient media. Yeast strains lacking ATX1 are deficient in high affinity iron uptake and expression of HAH1 in these strains permits growth on iron-depleted media and results in restoration of copper incorporation into newly synthesized Fet3p. These results identify HAH1 as a novel ubiquitously expressed protein, which may play an essential role in antioxidant defense and copper homeostasis in humans.
Highlights
The biological activation of dioxygen by copper is essential for the survival of all living organisms [1]
The sequence data reported in this study suggest that HAH1 is a human homologue of the S. cerevisiae copper-binding protein Atx1p
The considerable amino acid identity between these two proteins, including conservation of the MTCXGC copperbinding motif, as well as the occurrence of homologous sequences as open reading frames in the DNA of other diverse eukaryotic organisms, supports this concept and suggests a remarkable evolutionary conservation of the structure of this protein moiety similar to what has been observed for other proteins involved in copper homeostasis [2]
Summary
The biological activation of dioxygen by copper is essential for the survival of all living organisms [1]. To search for a mammalian homologue of ATX1, a human liver cDNA library was screened and a cDNA clone was isolated, which encodes a protein with 47% amino acid identity to Atx1p including conservation of the MTCXGC copper-binding domain.
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