ABCMdb

ABCA1 p.Lys2031Cys

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Publications

PMID: 23221702 [PubMed] Tomioka M et al: "The effects of neurological disorder-related codon variations of ABCA13 on the function of the ABC protein."

No. Sentence Comment

16 Two SNPs of ABCA13, T4031A and R4843C, were inserted into the corresponding amino acid residues of ABCA1, T1088A and K2031C. Login to comment
66 Hence we established HEK293 cells that stably expressed ABCA1 containing ABCA13 SNPs, ABCA1-T1088A, ABCA1- K2031C, and ABCA1-K2031R (as control). Login to comment
70 However, the K2031C SNP did not significantly affect cholesterol efflux as compared to the wild type or K2031R (Fig. 2A). Login to comment
71 ApoA-I binding of HEK/ABCA1-SNP mutants at the plasma membrane We have reported that the first step in high-density lipoprotein (HDL) formation is apoA-I binding to the extracellular domains of ABCA1.13) Hence we examined to determine whether the loss in the cholesterol efflux ability of T1088A was due to a change in apoA-I binding. Login to comment
73 W509S retained the ability to interact with apoA-I, while MM abolished that ability, as found previously.10) Furthermore, apoA-I binding was severely reduced (by 76%) by the T1088A SNP, while K2031C showed only a mild reduction (44%) (Fig. 2B). Login to comment
74 These results suggest that HEK/ABCA1-T1088A has low apoA-I-binding activity. Login to comment
79 For K2031C and wild-type K2031R, most of the protein was resistant to EndoH, but 50% or more of ABCA1-T1088 was sensitive to EndoH (Fig. 4), suggesting that the T1088A mutation caused improper folding of the protein. Login to comment
100 No SNPs have been reported at these positions in ABCA1, although more than 100 coding variants have been identified in ABCA1.15) Using PolyPhen-2, T1088A and K2031C were both predicted to impair the function of ABCA1, with scores of 1.000 and 0.999, respectively,16,17) but the effects of T1088A and K2031C replacement were quite different. Login to comment
101 T1088A severely impaired the subcellular localization and the functions of ABCA1, specifically apoA-I binding and cholesterol efflux, but K2031C showed only a mild effect on apoA-I binding, and no effect on cholesterol efflux. Login to comment
102 Based on the structure of mouse mdr1a,18) T1088A can be mapped at the interface between two NBDs and K2031 at the domain protruding to the outside (Fig. 6). Login to comment
106 On the other hand, K2031C did not affect the subcellular localization or cholesterol efflux of ABCA1. Login to comment
107 The R4843C replacement in the protruded domain of NBD2 in ABCA13 might have an effect Fig. 5. Login to comment
67 Hence we established HEK293 cells that stably expressed ABCA1 containing ABCA13 SNPs, ABCA1-T1088A, ABCA1- K2031C, and ABCA1-K2031R (as control). Login to comment
80 For K2031C and wild-type K2031R, most of the protein was resistant to EndoH, but 50% or more of ABCA1-T1088 was sensitive to EndoH (Fig. 4), suggesting that the T1088A mutation caused improper folding of the protein. Login to comment