ABCMdb

ABCB4 p.Leu481Arg

None has been submitted yet.

Publications

PMID: 24045840 [PubMed] Degiorgio D et al: "Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction."

No. Sentence Comment

2 Among subjects with cholangiopathies who were screened for mutations in ABCB4 by direct sequencing, we identified the new mutation p.(L481R) in three brothers. Login to comment
33 The plasmid pcDNA3.1/Hygro(&#fe; )/ABCB4 was also used to obtain clones harboring the p.(Y403H) or the p.(L481R) mutation. Login to comment
36 Bioinformatic analysis The three-dimensional models of the human MDR3 and of the p.Leu481Arg mutant were built by homology based on the structure of the murine multidrug resistance protein 1A (gene name, Abcb1a), determined with crystallographic methods (PDB: 3g5u).16 The models were built with an automated procedure with the SwissModel web server (http://www. Login to comment
54 RESULTS Molecular analysis and in silico evaluation The sequencing analysis of ABCB4 gene in the members of family A showed a new heterozygous mutation, c.1442T4G, which causes the p.(L481R) amino-acid change. Login to comment
56 The p.(L481R) replaces the hydrophobic Leu side chain with a bulkier and hydrophilic Arg residue in the first NBD. Login to comment
77 (b) Region surrounding the p.Leu481Arg mutation, with the neighboring residues represented in ball-and-stick. Login to comment
80 Wild-type cells secreted more PC and Chol than the mutant ones; PC: 3.417 nmol/mg proteins versus 1.410 for p.L481R and 2.346 for p.Y403H and Chol: 4.476 nmol/mg proteins versus 3.193 for p.L481R and 3.811 for p.Y403H (Figures 4a and b; Supplementary Table 1). Login to comment
82 Although wild-type cells and p.Y403H mutant showed similar fold increases in PC excretion, p.L481R mutant showed higher sensitivity to NaTC reaching 11-fold increase in PC secretion at 3 mM compared with the absence of NaTC (Supplementary Table 1). Login to comment
92 Lanes 5 and 6 show the stable expression of p.L481R-ABCB4 and p.Y403H, respectively. Login to comment
98 In this study, besides reporting the identification of a novel ABCB4 mutation (p.(L481R)) within the Q-loop in three siblings suffering from juvenile cholelithiasis, we demonstrate that this mutation, stably transfected in HUH28 cells, as well as the mutation p.(Y403H), previously described by our group,14 do not prevent protein targeting to the plasma membrane but induce an abnormal efflux of PC and Chol. Login to comment
102 The p.(L481R) mutation was identified in three out of seven affected siblings belonging to family A, whereas the already characterized p.(Y403H) mutation6,14 was identified in four affected members belonging to other two families. Login to comment
111 Analysis of PC (a) and Chol (b) secretion, and PC-Chol correlation (c) in MDR3 wild-type, MDR3 p.Y403H and MDR3 p.L481R cells. Login to comment

PMID: 24594635 [PubMed] Gordo-Gilart R et al: "Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity."

No. Sentence Comment

175 Along these lines, it has recently been reported that the mutation of another amino acid at the Q-loop of the NBD1 of MDR3, L481R, lowers MDR3 activity.26 The S978P mutation completely abrogated the PC translocation capacity of MDR3. Login to comment
174 Along these lines, it has recently been reported that the mutation of another amino acid at the Q-loop of the NBD1 of MDR3, L481R, lowers MDR3 activity.26 The S978P mutation completely abrogated the PC translocation capacity of MDR3. Login to comment

PMID: 24953525 [PubMed] Falguieres T et al: "ABCB4: Insights from pathobiology into therapy."

No. Sentence Comment

106 By contrast, the Y403H and L481R mutations did not alter membrane targeting but decreased ABCB4 activity [61]. Login to comment