ABCMdb

ABCA1 p.Ala937Val

None has been submitted yet.

Publications

PMID: 21697542 [PubMed] Lee JY et al: "ABCA1 increases extracellular ATP to mediate cholesterol efflux to ApoA-I."

No. Sentence Comment

11 Importantly, a dysfunctional ABCA1 mutant (A937V), when expressed similarly as wild-type ABCA1, is unable to raise extracellular ATP concentration, which suggests a casual relationship between functional ABCA1 and elevated extracellular ATP. Login to comment
61 BHK-A937V cells contain an ABCA1 gene insert carrying a single nucleotide A to V mutation. Login to comment
116 RESULTS To determine whether functional ABCA1 influences extracellular ATP levels, we analyzed ATP concentrations in the medium of BHK-ABCA1 cells and compared them with the medium collected from Mock-BHK or BHK-A937V cells. Login to comment
118 Specifically, BHK-ABCA1 cells carry the wild-type (WT) ABCA1 insert, whereas BHK-A937V cells carry an alanine to valine mutant within the first nucleotide-binding domain of the transporter (34). Login to comment
120 Once induced with mifepristone overnight, BHK-ABCA1 and BHK-A937V cells express ABCA1 or ABCA1A937V , respectively, at comparable levels but not BHK-Mock cells (Fig. 1A, right 3 lanes). Login to comment
145 Most interestingly, mifepristone does not alter the extracellular ATP concentration in BHK-A937V cells (Fig. 1C), although ABCA1A937V is similarly expressed as WT ABCA1. Login to comment
7 Importantly, a dysfunctional ABCA1 mutant (A937V), when expressed similarly as wild-type ABCA1, is unable to raise extracellular ATP concentration, which suggests a casual relationship between functional ABCA1 and elevated extracellular ATP. Login to comment
58 BHK-A937V cells contain an ABCA1 gene insert carrying a single nucleotide A to V mutation. Login to comment
112 RESULTS To determine whether functional ABCA1 influences extracellular ATP levels, we analyzed ATP concentrations in the medium of BHK-ABCA1 cells and compared them with the medium collected from Mock-BHK or BHK-A937V cells. Login to comment
114 Specifically, BHK-ABCA1 cells carry the wild-type (WT) ABCA1 insert, whereas BHK-A937V cells carry an alanine to valine mutant within the first nucleotide-binding domain of the transporter (34). Login to comment
140 Most interestingly, mifepristone does not alter the extracellular ATP concentration in BHK-A937V cells (Fig. 1C), although ABCA1A937V is similarly expressed as WT ABCA1. Login to comment

PMID: 18941142 [PubMed] Nandi S et al: "ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity."

No. Sentence Comment

5 For instance, a nucleotide binding domain mutation in ABCA1 (A937V) that impaired HDL generation also abolished microparticle release. Login to comment
151 A: 3 H-cholesterol labeled BHK-mock, ABCA1, ABCA1-A937V cells were induced for 20 h and incubated with DMEM without apoA-I for 4 h. B: 3 H-cholesterol labeled BHK-mock and ABCA1 were induced and incubated with DMEM with or without 50 mM PKI. Login to comment

PMID: 18776170 [PubMed] Vaughan AM et al: "ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation."

No. Sentence Comment

49 the first extracellular loop (V399A, R587W, W590S, and Q597R), two were in the second extracellular loop (C1477R and I1517R), and one was in the Walker A motif of the first nucleotide binding domain (A937V, NBD1) (Fig. 1). Login to comment
50 We also generated an artificial mutation in the Walker A motif of NBD2 (A1950V) that corresponds to the A937V mutation in NBD1. Login to comment
93 The two most severe mutations, which reduced apoA-I-mediated lipid efflux to less than 20% of normal, were located in the first extracellular loop (Q597R) and the ATP binding site (A937V). Login to comment
92 The two most severe mutations, which reduced apoA-I-mediated lipid efflux to less than 20% of normal, were located in the first extracellular loop (Q597R) and the ATP binding site (A937V). Login to comment

PMID: 17409096 [PubMed] Nagao K et al: "Enhanced apoA-I-dependent cholesterol efflux by ABCA1 from sphingomyelin-deficient Chinese hamster ovary cells."

No. Sentence Comment

165 The result by Landry et al., showing that a non-functional ABCA1 with mutation in the ATP-binding domain A937V fails to redistribute cholesterol, may support the latter model. Login to comment
163 The result by Landry et al., showing that a non-functional ABCA1 with mutation in the ATP-binding domain A937V fails to redistribute cholesterol, may support the latter model. Login to comment

PMID: 16984907 [PubMed] Landry YD et al: "ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions."

No. Sentence Comment

3 Cholesterol content in the plasma membraneis,however,notaltered.Moreover,weprovideevidence that a non-functional ABCA1 with mutation in an ATP-binding domain,A937V,failstoredistributecholesterol,sphingomyelin,or caveolin. Login to comment
4 A937V also fails to influence Akt activation. Login to comment
110 Cy3-Transferrin Labeling of EYFP-Caveolin-1-transfected Cells-Mock, ABCA1, and A937V mutant cells were grown in 35-mm glass-bottom dishes and transfected with EYFP-caveolin-1 as described above. Login to comment
118 Mock, ABCA1, and A937V mutant cells were grown to 80% confluence in 20-cm plates (five per cell line), and incubated in DMEM with 1 mg/ml BSA and 10 nM mifepristone for 18 h to induce ABCA1 expression. Login to comment
132 Subcellular [3 H]Cholesterol Distribution-Mock, ABCA1, and A937V mutant cells were grown to 80% confluence in 20-cm plates (two for each cell line). Login to comment
145 Briefly, mock, ABCA1, and A937V mutant cells were grown to 80% confluence in 20-cm plates. Login to comment
168 A, ABCA1 expression in Mock, ABCA1 and ABCA1 mutant, A937V, before (lane 1-3) and after over night incubation with 10 nM mifepristone (lane 4-12). Login to comment
191 ABCA1-expressing cells, however, seemed to have slightly less cholesterol in the endoplasmic reticulum (fractions 9 and 10) than Mock or A937V cells, which may reflect higher cholesterol mobility from internal membranes to the plasma membrane upon ABCA1 expression. Login to comment
193 We also included a BHK cell line that expresses a mutant form of ABCA1 (A937V) upon mifepristone induction. Login to comment
195 Cholesterol distribution in A937V-expressing cells was also identical to that of wt ABCA1-expressing or Mock cells (Fig. 2, FIGURE 2. Login to comment
197 A, ABCA1 distribution in Mock, ABCA1, and A937V cells. Login to comment
201 B, Mock, ABCA1, and A937V cells were stained with filipin, and fluorescent images were taken under identical conditions. Login to comment
207 A937V contains a naturally occurring mutation in its first ATP-binding domain and is not able to mediate cholesterol efflux (Fig. 1B). Login to comment
210 Mock, ABCA1, and A937V cells were treated with ice-cold Triton X-100 (1%) for 30 min. Login to comment
220 To address this, we used BHK cells expressing A937V. Login to comment
221 The cold Triton X-100-extractable cholesterol fraction in A937V-expressing cells was identical to that in Mock cells (Fig. 3, A and B), indicating that cholesterol redistribution from raft to non-rafts requires functional ABCA1 protein. Login to comment
226 Once again, the A937V mutant failed to redistribute [3 H]sphingomyelin, consistent with its incapability to redistribute cholesterol in these cells. Login to comment
238 We transiently transfected Mock, ABCA1, and A937V cells with YFP-caveolin. Login to comment
242 BHK cells induced to express either empty vector (Mock), ABCA1 (ABCA1), or ABCA1 mutant A937V (A937V) cells were incubated with mifepristone overnight and subjected to 1% cold Triton X-100 extraction for 30 min on ice. Login to comment
248 C and D, Mock, ABCA1, and A937V cells were radiolabeled with 1 ␮Ci/ml [3 H]choline for 24 h, chilled on ice for 30 min prior to 1% Triton X-100 extraction at 4 °C. Login to comment
277 Furthermore, when we tested ABCA1 mutant A937V, we found that A937V was mainly localized on the plasma membrane and expressed at levels similar to wild-type ABCA1 (Fig. 6C). Login to comment
279 YFP-caveolin in A937V cells was mostly clustered, identical to that in Mock cells. Login to comment
280 This is consistent with our observations presented above that A937V is defective in redistributing rafts (Fig. 3). Login to comment
291 We therefore performed experiments using a non- detergent-based method, Optiprep gradient floatation, on Mock, ABCA1, and A937V cells (Fig. 7A). Login to comment
293 A minor portion of caveolin (ϳ5%) was found in fractions 7-9, co-localizing with clathrin, a non-raft maker, in Mock and A937V cells. Login to comment
294 However, there was much more caveolin in the non-raft fractions (20%) in ABCA1 cells than either Mock or A937V cells (Fig. 7B). Login to comment
295 There was no significant difference between Mock and A937V cells. Login to comment
300 BHK cells expressing either wt ABCA1 or A937V were transfected with YFP-caveolin and immunostained for ABCA1. Login to comment
305 Mock, ABCA1, and A937V cells were induced overnight with mifepristone, and membrane fractions were isolated as described under "Materials and Methods." Login to comment
307 B, the Western blots were scanned and analyzed for Mock, ABCA1, and A937V cells. Login to comment
313 Expression of A937V once again does not alter Akt activation (Fig. 8A). Login to comment
330 Mock, ABCA1, and A937V cells were induced and serum-starved overnight before EGF treatment. Login to comment
358 Most importantly, we found that a functional nucleotide-binding domain in ABCA1 is required for non-raft expansion, because the A937V mutant failed to induce any cholesterol, sphingomyelin, or caveolin redistribution. Login to comment
359 A937V mutant also failed to impair Akt phosphorylation. Login to comment
378 Our observations with the A937V mutant seem to support this later notion. Login to comment
192 ABCA1-expressing cells, however, seemed to have slightly less cholesterol in the endoplasmic reticulum (fractions 9 and 10) than Mock or A937V cells, which may reflect higher cholesterol mobility from internal membranes to the plasma membrane upon ABCA1 expression. Login to comment
194 We also included a BHK cell line that expresses a mutant form of ABCA1 (A937V) upon mifepristone induction. Login to comment
196 Cholesterol distribution in A937V-expressing cells was also identical to that of wt ABCA1-expressing or Mock cells (Fig. 2, FIGURE 2. Login to comment
198 A, ABCA1 distribution in Mock, ABCA1, and A937V cells. Login to comment
202 B, Mock, ABCA1, and A937V cells were stained with filipin, and fluorescent images were taken under identical conditions. Login to comment
208 A937V contains a naturally occurring mutation in its first ATP-binding domain and is not able to mediate cholesterol efflux (Fig. 1B). Login to comment
211 Mock, ABCA1, and A937V cells were treated with ice-cold Triton X-100 (1%) for 30 min. Login to comment
222 The cold Triton X-100-extractable cholesterol fraction in A937V-expressing cells was identical to that in Mock cells (Fig. 3, A and B), indicating that cholesterol redistribution from raft to non-rafts requires functional ABCA1 protein. Login to comment
227 Once again, the A937V mutant failed to redistribute [3 H]sphingomyelin, consistent with its incapability to redistribute cholesterol in these cells. Login to comment
239 We transiently transfected Mock, ABCA1, and A937V cells with YFP-caveolin. Login to comment
243 BHK cells induced to express either empty vector (Mock), ABCA1 (ABCA1), or ABCA1 mutant A937V (A937V) cells were incubated with mifepristone overnight and subjected to 1% cold Triton X-100 extraction for 30 min on ice. Login to comment
249 C and D, Mock, ABCA1, and A937V cells were radiolabeled with 1 òe;Ci/ml [3 H]choline for 24 h, chilled on ice for 30 min prior to 1% Triton X-100 extraction at 4 &#b0;C. Login to comment
377 Our observations with the A937V mutant seem to support this later notion. Login to comment

PMID: 16704350 [PubMed] Brunham LR et al: "Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis."

No. Sentence Comment

555 Since a complete loss of function allele would be expected to result in a 50% reduction in HDL levels, a greater than 50% reduction in HDL is most likely explained by a dominant negative allele, in which TABLE 3 Patient phenotypes associated with heterozygous ABCA1 mutations Mutation HDL (mmol/L) HDL (% of control) Number of patients M1091T 0.48 ± 0.5 30 ± 30 4 G1216V 0.50 40 1 R2144X 0.56 ± 0.2 41 ± 18 12 R282X 0.52 41 1 R909X 0.59 ± 0.3 42 ± 19 5 K776N 0.55 ± 0.1 47 ± 5 2 R587W 0.61 ± 0.1 47 ± 8 7 S364C 0.60 48 1 P1065S 0.80 51 1 c-ter deletion 0.75 53 1 N1800H - 56.5 33 P85L 0.72 ± 0.4 57 ± 33 5 Del693L 0.79 ± 0.2 57 ± 15 8 D1289N 0.80 ± 0.1 59 ± 12 4 R2081W 0.80 ± 0.1 59 ± 12 4 2203X 0.80 ± 0.2 59 ± 20 4 DelED1893,4 0.77 ± 0.2 59 ± 18 8 2145X 0.82 ± 0.1 59 ± 9 4 A1046D 0.70 ± 0.1 60 ± 8 2 Q597R 0.82 ± 0.1 60 ± 5 5 C1477R 0.82 ± 0.2 61 ± 15 9 IVS25 + 1G > C 0.78 ± 0.1 62 ± 12 4 D1099Y 0.83 ± 0.3 63 ± 21 5 1552X 1.00 64 1 F2009S 0.82 ± 0.2 64 ± 19 6 R587W 0.86 ± 0.1 65 ± 17 2 R1068H 0.90 ± 0.3 67 ± 26 9 N935S 1.00 ± 0.3 74 ± 16 7 T929I 1.01 ± 0.2 76 ± 7 8 1284X 1.11 ± 0.2 83 ± 14 5 A937V 1.15 ± 0.6 85 ± 28 2 R1680W 1.22 ± 0.2 87 ± 17 3 635X 1.24 ± 0.5 90 ± 32 7 W590S 1.32 ± 0.6 103 ± 46 15 the mutant protein actually interferes with the activity of the remaining wild-type protein. Login to comment

PMID: 16429166 [PubMed] Brunham LR et al: "Accurate prediction of the functional significance of single nucleotide polymorphisms and mutations in the ABCA1 gene."

No. Sentence Comment

48 This SNP has been reported to be associated with decreased HDL cholesterol and increased severity of atherosclerosis in Table 1. subPSEC Scores and Probability of Functional Impairment (Pdeleterious) for ABCA1 Mutations and SNPs Mutations SNPs Variant SubPSEC Pdeleterious Variant subPSEC Pdeleterious P85L À4.62 0.83 R219K À0.57 0.08 H160F À2.79 0.45 V399A À2.26 0.32 R230C À4.27 0.78 V771M À2.86 0.46 A255T À1.81 0.23 T774P À1.99 0.27 E284K À2.34 0.34 K776N À3.53 0.63 Y482C À4.21 0.77 V825I À1.06 0.13 R587W À6.04 0.95 I883M À1.38 0.17 W590S À5.19 0.9 E1172D À1.96 0.26 W590L À4.48 0.82 R1587K À0.58 0.08 Q597R À7.15 0.98 S1731C À4.21 0.77 T929I À4.29 0.78 N935H À8.54 1 N935S À7.53 0.99 A937V À6.6 0.97 A1046D À7.52 0.99 M1091T À3.56 0.64 D1099Y À6.09 0.96 D1289N À2.48 0.37 L1379F À3.81 0.69 C1477R À5.44 0.92 S1506L À5.17 0.9 N1611D À5.69 0.94 R1680W À6.02 0.95 V1704D À3.21 0.55 N1800H À4.23 0.77 R1901S À5.06 0.89 F2009S À2.73 0.43 R2081W À8.08 0.99 P2150L À2.88 0.47 Q2196H À2.74 0.43 DOI: 10.1371/journal.pgen.0010083.t001 PLoS Genetics | www.plosgenetics.org December 2005 | Volume 1 | Issue 6 | e83 0740 Accurate Prediction of ABCA1 Variants Synopsis A major goal of human genetics research is to understand how genetic variation leads to differences in the function of genes. Login to comment

PMID: 12763760 [PubMed] Singaraja RR et al: "Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene."

No. Sentence Comment

83 TABLE 2. Conservation of Amino Acid Residues Mutated in Humans Mutation H. sapiens M. musculus G. gallus D. melanogaster C. elegans P85L P P P ⅐ ⅐ ⅐ P R230C R R R P G A255T A A S ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ R587W R R R ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ W590S W W W R Q Q597R Q Q Q Q Q ⌬L693 L L L L L T929I T T T T T N935S/H N N N N N A937V A A A A A A1046D A A A A A M1091T M M M M M D1099Y D D D D D D1289L/N D D D D D C1477R C C C ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ S1506L S S S ⅐ ⅐ ⅐ ⅐ ⅐ ⅐ N1611D N N N N S R1680W R R R R R N1800H N N N A W F2009S F F F I M R2081W R R R R R P2150L P P P R N ⌬E1893 E E E D S ⌬D1894 D D D D D Twenty-three of 24 (95.83%) amino acids affected by mutations are conserved with G. gallus, reflecting the functional importance of these residues. Login to comment
114 Patients homozygous for the mutations A255T and R1680W show HDL-C levels that are greater than 10% of age-and sex-matched population controls. Login to comment
122 This is indeed the case in heterozygous patients harboring mutations A255T, W590S, T929I, R1680W, and A937V, who all show HDL-C levelsϾ75% of normal age-and sex-matched controls. Login to comment
75 TABLE 2. Conservation of Amino Acid Residues Mutated in Humans Mutation H. sapiens M. musculus G. gallus D. melanogaster C. elegans P85L P P P ዼ ዼ ዼ P R230C R R R P G A255T A A S ዼ ዼ ዼ ዼ ዼ ዼ R587W R R R ዼ ዼ ዼ ዼ ዼ ዼ W590S W W W R Q Q597R Q Q Q Q Q èc;L693 L L L L L T929I T T T T T N935S/H N N N N N A937V A A A A A A1046D A A A A A M1091T M M M M M D1099Y D D D D D D1289L/N D D D D D C1477R C C C ዼ ዼ ዼ ዼ ዼ ዼ S1506L S S S ዼ ዼ ዼ ዼ ዼ ዼ N1611D N N N N S R1680W R R R R R N1800H N N N A W F2009S F F F I M R2081W R R R R R P2150L P P P R N èc;E1893 E E E D S èc;D1894 D D D D D Twenty-three of 24 (95.83%) amino acids affected by mutations are conserved with G. gallus, reflecting the functional importance of these residues. Login to comment

PMID: 12840658 [PubMed] Miller M et al: "Genetics of HDL regulation in humans."

No. Sentence Comment

66 TD 1591 T/C 11 V399A extracellular [68] TD 1979 (110bpAlu Ins) 12 truncated truncation [60] TD/FHA 2154 C/T 14 R587W extracellular [67,69] TD 2164 G/C 14 W590S extracellular [61] TD 2185 A/G 14 Q597R extracellular [59,67] TD 2219 G/del 14 truncated, 635X truncated [60,61] FHA 2472-2474 3bp del 15 Del L693 TM domain #3 [59] phosphorylation 2706 G/A 16 V771M extracellular [68] 2715 A/C 16 T774P extracellular [68] 2723 G/C 16 K776N extracellular [68] 2868 G/A 17 V825I TM domain #6 [67,68] TD/FHA 3044 A/G 18 I883M cytoplasmic [68] phosphorylat site FHA 3120 C/T 19 R909X truncation [63,71] TD 3181 C/T 19 T929I cytoplasmic [62] TD 3199 A/G 19 N935S Walker A [61] TD 3205 C/T 19 A937V Walker A [61] TD 3532 C/A 22 A1046D cytoplasmic, Walker A/B [70] FHA 3667 T/C 23 M1091T cytoplasmic [63] 3690 G/T 23 D1099Y cytoplasmic [9] TD 3738 2bp del 23 1145X truncation [66] FHA 3911 G/C 24 E1172D linker/cytoplasmic [68] FHA 4242 4bp del 27 1297X truncated [64] TD 4260 G/A 27 D1289N linker cytoplasm [64,65] TD 4824 T/C 31 C1477R extracellular [59] TD 4912 C/T 32 S1506L extracellular loop #2 [71] TD 5025 ins A 34 A1544S?1552X truncation [70] 5059 T/C 34 I1555T extracellular loop #2 [67] 5155 G/A 35 R1587K extracellular loop #2 [68] FHA 5226 A/G 36 N1611D extracellular loop #2 [75..] 5338 T/C 36 L1648P extracellular loop #2 [67] TD 5443 C/T 37 R1680W cytoplasmic [74.] Login to comment

PMID: 12111381 [PubMed] Guo Z et al: "Double deletions and missense mutations in the first nucleotide-binding fold of the ATP-binding cassette transporter A1 ( ABCA1) gene in Japanese patients with Tangier disease."

No. Sentence Comment

86 The Ala937Val mutation in Walker A motif (Bodzioch et al. 1999) and Ala1046Asp near Walker B motif (Wang et al. 2000) of the first NBF have been reported. Login to comment

PMID: 23055522 [PubMed] Ma L et al: "ABCA1 protein enhances Toll-like receptor 4 (TLR4)-stimulated interleukin-10 (IL-10) secretion through protein kinase A (PKA) activation."

No. Sentence Comment

106 A nonfunctional ABCA1 mutant, A937V, failed to increase p-CREB despite being expressed at a similar level as WT ABCA1 (Fig. 2A) with correct targeting to the plasma membrane (21). Login to comment

PMID: 25415591 [PubMed] Dong F et al: "Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1."

No. Sentence Comment

64 BHK cells stably expressing an mifepristone-inducible vector with human ABCA1 (ABCA1) or mutant A937V ABCA1 (A937V) gene insert were prepared as described previously [26]. Login to comment
121 It has little effect on BHK cells with no ABCA1 expression (data not shown) or BHK cells expressing a dysfunctional mutant form of ABCA1 (A937V) (Fig. 1 C). Login to comment
150 C) BHK-ABCA1 and BHK-A937V cells were induced with mifepristone (10 nM) overnight. Login to comment