ABCMdb

PMID: 11050011

Bekri S, Kispal G, Lange H, Fitzsimons E, Tolmie J, Lill R, Bishop DF
Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation.
Blood. 2000 Nov 1;96(9):3256-64., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCB7 p.Glu433Lys 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. Login to comment 6 ABCB7 p.Glu433Lys 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. Login to comment 8 ABCB7 p.Glu433Lys In contrast, the expression of mutated ABC7 (E433K) or Atm1p (D398K) proteins in èc;atm1 cells led to a low efficiency of cytosolic Fe/S protein maturation. Login to comment 9 ABCB7 p.Glu433Lys In contrast, the expression of mutated ABC7 (E433K) or Atm1p (D398K) proteins in ⌬atm1 cells led to a low efficiency of cytosolic Fe/S protein maturation. Login to comment 160 ABCB7 p.Glu433Lys The mutation resulted in a substitution of lysine for the wild-type glutamate at amino acid 433 (E433K) of the ABC7 protein and abolished a BsmAI restriction site (Figure 1D). Login to comment 164 ABCB7 p.Glu433Lys The mutation resulted in a substitution of lysine for the wild-type glutamate at amino acid 433 (E433K) of the ABC7 protein and abolished a BsmAI restriction site (Figure 1D). Login to comment 165 ABCB7 p.Glu433Lys In addition, we performed similar studies with Atm1p into which the mutation corresponding to the human ABC7 mutant (E433K) was introduced (Atm1p D398K). Login to comment 166 ABCB7 p.Glu433Lys Wild-type Atm1p and, to a slightly lesser extent, ABC7 complemented the growth defect of èc;atm1 cells and the defect leading to mitochondrial iron accumulation.12 Similarly, both the Atm1p D398K and the ABC7 E433K mutant proteins restored growth of èc;atm1 cells to a similar extent as the corresponding wild-type proteins (data not shown). Login to comment 169 ABCB7 p.Glu433Lys In addition, we performed similar studies with Atm1p into which the mutation corresponding to the human ABC7 mutant (E433K) was introduced (Atm1p D398K). Login to comment 170 ABCB7 p.Glu433Lys Wild-type Atm1p and, to a slightly lesser extent, ABC7 complemented the growth defect of ⌬atm1 cells and the defect leading to mitochondrial iron accumulation.12 Similarly, both the Atm1p D398K and the ABC7 E433K mutant proteins restored growth of ⌬atm1 cells to a similar extent as the corresponding wild-type proteins (data not shown). Login to comment 173 ABCB7 p.Glu433Lys Finally, we investigated the consequences of the XLSA/A mutation E433K in ABC7 and the corresponding mutation in Atm1p (D398K) for the function of these proteins in cytosolic Fe/S protein maturation. Login to comment 177 ABCB7 p.Glu433Lys Finally, we investigated the consequences of the XLSA/A mutation E433K in ABC7 and the corresponding mutation in Atm1p (D398K) for the function of these proteins in cytosolic Fe/S protein maturation. Login to comment 202 ABCB7 p.Ile400Met These results represent the second mutation in the human ABC7 gene and therefore confirm and extend the previous identification of an ABC7 mutation (1208T3G) that substituted a methionine for an isoleucine at codon 400 in exon 9 as the cause of XLSA/A. Login to comment 206 ABCB7 p.Glu433Lys ABCB7 p.Ile400Met These results represent the second mutation in the human ABC7 gene and therefore confirm and extend the previous identification of an ABC7 mutation (1208T3G) that substituted a methionine for an isoleucine at codon 400 in exon 9 as the cause of XLSA/A. Login to comment 210 ABCB7 p.Glu433Lys The E433K mutation in ABC7 identified in this XLSA/A family impaired the function of the protein in cytosolic Fe/S protein assembly. Login to comment