Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation.
The human protein ABC7 belongs to the adenosine triphosphate-binding cassette transporter superfamily, and its yeast orthologue, Atm1p, plays a central role in the maturation of cytosolic iron-sulfur (Fe/S) cluster-containing proteins. Previously, a missense mutation in the human ABC7 gene was shown to be the defect in members of a family affected with X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A). Here, the promoter region and the intron/exon structure of the human ABC7 gene were characterized, and the function of wild-type and mutant ABC7 in cytosolic Fe/S protein maturation was analyzed. The gene contains 16 exons, all with intron/exon boundaries following the AG/GT rule. A single missense mutation was found in exon 10 of the ABC7 gene in 2 affected brothers with XLSA/A. The mutation was a G-to-A transition at nucleotide 1305 of the full-length cDNA, resulting in a charge inversion caused by the substitution of lysine for glutamate at residue 433 C-terminal to the putative sixth transmembrane domain of ABC7. Expression of normal ABC7 almost fully complemented the defect in the maturation of cytosolic Fe/S proteins in a yeast strain in which the ATM1 gene had been deleted (Deltaatm1 cells). Thus, ABC7 is a functional orthologue of Atm1p. In contrast, the expression of mutated ABC7 (E433K) or Atm1p (D398K) proteins in Deltaatm1 cells led to a low efficiency of cytosolic Fe/S protein maturation. These data demonstrate that both the molecular defect in XLSA/A and the impaired maturation of a cytosolic Fe/S protein result from an ABC7 mutation in the reported family.[1]References
- Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Bekri, S., Kispal, G., Lange, H., Fitzsimons, E., Tolmie, J., Lill, R., Bishop, D.F. Blood (2000) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
