ABCA1 p.Glu2254Ala
Predicted by SNAP2: | A: N (66%), C: N (53%), D: N (72%), F: D (59%), G: N (53%), H: N (61%), I: N (61%), K: N (61%), L: N (66%), M: N (82%), N: N (78%), P: N (53%), Q: N (78%), R: N (72%), S: N (72%), T: N (78%), V: N (66%), W: D (63%), Y: D (59%), |
Predicted by PROVEAN: | A: N, C: N, D: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Liver X receptor beta (LXRbeta) interacts directly... J Biol Chem. 2011 Jun 3;286(22):20117-24. Epub 2011 Apr 20. Hozoji-Inada M, Munehira Y, Nagao K, Kioka N, Ueda K
Liver X receptor beta (LXRbeta) interacts directly with ATP-binding cassette A1 (ABCA1) to promote high density lipoprotein formation during acute cholesterol accumulation.
J Biol Chem. 2011 Jun 3;286(22):20117-24. Epub 2011 Apr 20., [PMID:21507939]
Abstract [show]
Cells have evolved multiple mechanisms for maintaining cholesterol homeostasis, and, among these, ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux is highly regulated at the transcriptional level through the activity of the nuclear receptor liver X receptor (LXR). Here, we show that in addition to its well defined role in transcription, LXRbeta directly binds to the C-terminal region ((2247)LTSFL(2251)) of ABCA1 to mediate its post-translational regulation. In the absence of cholesterol accumulation in the macrophage-like cell line THP-1, the ABCA1-LXRbeta complex stably localizes to the plasma membrane, but apolipoprotein A-I (apoA-I) binding or cholesterol efflux does not occur. Exogenously added LXR ligands, which mimic cholesterol accumulation, cause LXRbeta to dissociate from ABCA1, thus freeing ABCA1 for apoA-I binding and subsequent cholesterol efflux. Photoaffinity labeling experiments with 8-azido-[alpha-(32)P]ATP showed that the interaction of LXRbeta with ABCA1 inhibits ATP binding by ABCA1. This is the first study to show that a protein-protein interaction with the endogenous protein suppresses the function of ABC proteins by inhibiting ATP binding. LXRbeta can cause a post-translational response by binding directly to ABCA1, as well as a transcriptional response, to maintain cholesterol homeostasis.
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No. Sentence Comment
86 As a control, a construct in which Glu2254 was replaced with alanine was generated.
X
ABCA1 p.Glu2254Ala 21507939:86:35
status: NEW85 As a control, a construct in which Glu2254 was replaced with alanine was generated.
X
ABCA1 p.Glu2254Ala 21507939:85:35
status: NEW