ABCMdb

ABCA3 p.Thr1114Ala

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Publications

PMID: 18676873 [PubMed] Matsumura Y et al: "Aberrant catalytic cycle and impaired lipid transport into intracellular vesicles in ABCA3 mutants associated with nonfatal pediatric interstitial lung disease."

No. Sentence Comment

175 L702 CHARACTERIZATION OF ABCA3 MUTANTS ASSOCIATED WITH pILD AJP-Lung Cell Mol Physiol • VOL 295 • OCTOBER 2008 • www.ajplung.org intermediate during ATP hydrolysis was decreased to 37% of that of wild-type protein, as also was the case in E292V mutant protein (Fig. 4B, lanes 5-8, and C). Login to comment
178 Recently, we identified a novel compound heterozygous mutation (maternal T1114A and paternal W1148X) from a Japanese boy with respiratory distress from age 18 mo (37). Login to comment
179 The T1114A mutation decreased vanadate-induced nucleotide trapping by ABCA3 protein similarly to the T1114M mutation. Login to comment
182 In vanadate-induced nucleotide trapping by T1114S mutant protein, production of a photoaffinity-labeled intermediate during ATP hydrolysis was found to be similar to that of wild-type protein, whereas that of T1114M and T1114A mutant protein was 56 and 47% of wild-type protein, respectively (Fig. 5B, lanes 5-10, and C). Login to comment
183 These results indicate that loss of the hydroxyl group of the 1114th amino acid is responsible for the impaired ATP hydrolysis with production of a photoaffinity-labeled intermediate in both the T1114M and T1114A mutant proteins. Login to comment
195 The amino acids residues that are conserved in 6 transporters and in 4 or 5 transporters are indicated by asterisks and dots, respectively. B: 20,000-g membrane fraction prepared from HEK-293 cells stably expressing the WT ABCA3-GFP (lanes 3 and 4), T1114M (lanes 5 and 6), T1114A (lanes 7 and 8), T1114S (lanes 9 and 10), or untransfected HEK-293 cells (lanes 1 and 2) was incubated with 10 ␮M 8-azido-[␣-32 P]ATP in the absence or presence of 0.4 mM Vi and 3 mM MgCl2 for 10 min at 37°C. Login to comment
232 Accordingly, E292V, E690K, and T1114M are type II mutations. Login to comment
235 Although an exception has been identified in a Japanese patient with a type I/type II ABCA3 mutation (W1148X/T1114A) (37), the moderately preserved lipid transport function of the E292V mutant protein may underlie the generally milder phenotype of pILD patients. Login to comment
252 Genotype-phenotype correlation for ABCA3 mutation ABCA3 Mutation Age of Symptoms Phenotype Ref. W1142X W1142X Neonate FSD 27 L101P L101P Neonate FSD 27 L1553P L1553P Neonate FSD 27 Ins1518 L1580P Neonate FSD 27 L982P G1221S Neonate FSD 27 E292V T1114M Neonate pILD 4 E292V E690K 5 or 7 yr pILD 4 W1148X T1114A 12 mo pILD 37 Type I and type II ATP binding cassette A3 (ABCA3) mutations are shown in italics and roman, respectively. Login to comment
174 Recently, we identified a novel compound heterozygous mutation (maternal T1114A and paternal W1148X) from a Japanese boy with respiratory distress from age 18 mo (37). Login to comment
191 The amino acids residues that are conserved in 6 transporters and in 4 or 5 transporters are indicated by asterisks and dots, respectively. B: 20,000-g membrane fraction prepared from HEK-293 cells stably expressing the WT ABCA3-GFP (lanes 3 and 4), T1114M (lanes 5 and 6), T1114A (lanes 7 and 8), T1114S (lanes 9 and 10), or untransfected HEK-293 cells (lanes 1 and 2) was incubated with 10 òe;M 8-azido-[ॷ-32 P]ATP in the absence or presence of 0.4 mM Vi and 3 mM MgCl2 for 10 min at 37&#b0;C. Login to comment
249 Genotype-phenotype correlation for ABCA3 mutation ABCA3 Mutation Age of Symptoms Phenotype Ref. W1142X W1142X Neonate FSD 27 L101P L101P Neonate FSD 27 L1553P L1553P Neonate FSD 27 Ins1518 L1580P Neonate FSD 27 L982P G1221S Neonate FSD 27 E292V T1114M Neonate pILD 4 E292V E690K 5 or 7 yr pILD 4 W1148X T1114A 12 mo pILD 37 Type I and type II ATP binding cassette A3 (ABCA3) mutations are shown in italics and roman, respectively. Login to comment

PMID: 17618459 [PubMed] Yokota T et al: "Heterozygous ABCA3 mutation associated with non-fatal evolution of respiratory distress."

No. Sentence Comment

4 Analysis of the ATP-binding cassette transporter A3 (ABCA3; OMIM 601615) gene showed a compound heterozygous mutation from paternal W1148X and maternal T1114A. Login to comment
27 Direct sequence analysis of ABCA3 in the patient revealed a compound heterozygous mutation, W1148X on the paternal allele and T1114A on the maternal allele. Login to comment
28 In vitro study showed that the T1114A mutant had moderately preserved ATP-hydrolysis activity (51% of wild type) with normal intracellular localization, while the W1148X mutant had impaired intracellular localization. Login to comment
29 W1148X is a type I, loss-of-function mutation (abnormal intracellular localization) and T1114A is a type II mutation (normal intracellular localization with decreased ATP-hydrolysis activity) [2]. Login to comment
41 In this case, the moderately preserved ATP-hydrolysis activity of the T1114A mutant may underlie the milder symptoms and later onset of respiratory failure than in fatal newborn surfactant deficiency. Login to comment
42 Because ATP-hydrolysis activity of ABCA3 protein is regulated by lipids [3], exogenous surfactant lipid itself might rescue the activity of the T1114A mutant protein. Login to comment