ABCA1 p.Gln71Leu
Predicted by SNAP2: | A: D (71%), C: D (75%), D: D (85%), E: D (75%), F: D (80%), G: D (85%), H: D (80%), I: D (85%), K: D (63%), L: D (85%), M: D (75%), N: D (80%), P: D (85%), R: D (85%), S: D (75%), T: D (71%), V: D (75%), W: D (85%), Y: D (80%), |
Predicted by PROVEAN: | A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] ADP-ribosylation factor (ARF)-like 7 (ARL7) is ind... FEBS Lett. 2004 May 21;566(1-3):241-6. Engel T, Lueken A, Bode G, Hobohm U, Lorkowski S, Schlueter B, Rust S, Cullen P, Pech M, Assmann G, Seedorf U
ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export.
FEBS Lett. 2004 May 21;566(1-3):241-6., [PMID:15147902]
Abstract [show]
Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF- and ARL-family member whose mRNA-expression is induced by liver X-receptor/retinoid X-receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7-enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over-expression on the cholesterol secretory pathway. We found that expression of wild type and dominant active ARL7-EGFP stimulated the rate of apolipoprotein AI-specific cholesterol efflux 1.7- and 2.8-fold. In contrast, expression of the dominant negative form of ARL7-EGFP led to approximately 50% inhibition of cholesterol efflux. This data is consistent with a model in which ARL7 is involved in transport between a perinuclear compartment and the plasma membrane apparently linked to the ABCA1-mediated cholesterol secretion pathway.
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No. Sentence Comment
106 ARL7(G2A) lacks a myristoylation site, ARL(T27N) represents the inactive GDP-bound (dominant negative) and ARL7(Q71L) the active GTP-bound state (dominant active).
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ABCA1 p.Gln71Leu 15147902:106:112
status: NEW121 Conversely, the Q71L mutant resulted in a very similar staining pattern and affected the cellular morphology the same way as wt ARL7 with less filopodia (Fig. 4D).
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ABCA1 p.Gln71Leu 15147902:121:16
status: NEW137 (A) ARL7(wt), (B) ARL7(G2A), (C) ARL7(T27N), (D) ARL7(Q71L).
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ABCA1 p.Gln71Leu 15147902:137:54
status: NEW163 Over-expression of the two ARL7 forms (ARL7-EGFP and ARL7(Q71L)-EGFP) which stimulated cholesterol efflux were associated with quite extensive alterations of cell morphology.
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ABCA1 p.Gln71Leu 15147902:163:58
status: NEW165 We presume that some of these changes may have been due to accumulation of ARL7-EGFP and ARL7(Q71L)-EGFP at the terminus of their transport route, presumably as a consequence of a very slow return to their starting point.
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ABCA1 p.Gln71Leu 15147902:165:94
status: NEW[hide] BIG1, a brefeldin A-inhibited guanine nucleotide-e... Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):e31-8. doi: 10.1161/ATVBAHA.112.300720. Epub 2012 Dec 6. Lin S, Zhou C, Neufeld E, Wang YH, Xu SW, Lu L, Wang Y, Liu ZP, Li D, Li C, Chen S, Le K, Huang H, Liu P, Moss J, Vaughan M, Shen X
BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein modulates ATP-binding cassette transporter A-1 trafficking and function.
Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):e31-8. doi: 10.1161/ATVBAHA.112.300720. Epub 2012 Dec 6., [PMID:23220274]
Abstract [show]
OBJECTIVE: Cell-surface localization and intracellular trafficking are essential for the function of ATP-binding cassette transporter A-1 (ABCA1). However, regulation of these activities is still largely unknown. Brefeldin A, an uncompetitive inhibitor of brefeldin A-inhibited guanine nucleotide-exchange proteins (BIGs), disturbs the intracellular distribution of ABCA1, and thus inhibits cholesterol efflux. This study aimed to define the possible roles of BIGs in regulating ABCA1 trafficking and cholesterol efflux, and further to explore the potential mechanism. METHODS AND RESULTS: By vesicle immunoprecipitation, we found that BIG1 was associated with ABCA1 in vesicles preparation from rat liver. BIG1 depletion reduced surface ABCA1 on HepG2 cells, and inhibited by 60% cholesterol release. In contrast, BIG1 overexpression increased surface ABCA1 and cholesterol secretion. With partial restoration of BIG1 through overexpression in BIG1-depleted cells, surface ABCA1 was also restored. Biotinylation and glutathione cleavage revealed that BIG1 small interfering RNA dramatically decreased the internalization and recycling of ABCA1. This novel function of BIG1 was dependent on the guanine nucleotide-exchange activity and achieved through activation of ADP-ribosylation factor 1. CONCLUSIONS: BIG1, through its ability to activate ADP-ribosylation factor 1, regulates cell-surface levels and function of ABCA1, indicating a transcription-independent mechanism for controlling ABCA1 action.
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No. Sentence Comment
83 Cells overexpressing ARF1-Q71L, which is assumed to be constitutively active with GTP-bound, or WT-ARF1, showed increased surface ABCA1.
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ABCA1 p.Gln71Leu 23220274:83:26
status: NEW84 In addition, ARF-Q71L stimulated a much greater surface distribution of ABCA1 than ARF1-WT.
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ABCA1 p.Gln71Leu 23220274:84:17
status: NEW88 An increased cholesterol content was found in cells overexpressing Arf1-WT and Arf1-Q71L (Figure 5C).
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ABCA1 p.Gln71Leu 23220274:88:84
status: NEW