ABCC7 p.Met156Val
Predicted by SNAP2: | A: D (71%), C: N (57%), D: D (91%), E: D (91%), F: D (80%), G: D (85%), H: D (85%), I: N (53%), K: D (91%), L: N (78%), N: D (85%), P: D (91%), Q: D (80%), R: D (91%), S: D (85%), T: D (85%), V: N (53%), W: D (91%), Y: D (85%), |
Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: N, G: D, H: D, I: N, K: D, L: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Deletion of CFTR translation start site reveals fu... Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4. Ramalho AS, Lewandowska MA, Farinha CM, Mendes F, Goncalves J, Barreto C, Harris A, Amaral MD
Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.
Cell Physiol Biochem. 2009;24(5-6):335-46. Epub 2009 Nov 4., [PMID:19910674]
Abstract [show]
BACKGROUND/AIMS: Mutations in the CFTR gene cause Cystic Fibrosis (CF) the most common life-threatening autosomal recessive disease affecting Caucasians. We identified a CFTR mutation (c.120del23) abolishing the normal translation initiation codon, which occurs in two Portuguese CF patients. This study aims at functionally characterizing the effect of this novel mutation. METHODS: RNA and protein techniques were applied to both native tissues from CF patients and recombinant cells expressing CFTR constructs to determine whether c.120del23 allows CFTR protein production through usage of alternative internal codons, and to characterize the putative truncated CFTR form(s). RESULTS: Our data show that two shorter forms of CFTR protein are produced when the initiation translation codon is deleted indicating usage of internal initiation codons. The N-truncated CFTR generated by this mutation has decreased stability, very low processing efficiency, and drastically reduced function. Analysis of mutants of four methionine codons downstream to M1 (M82, M150, M152, M156) revealed that each of the codons M150/M152/M156 (exon 4) can mediate CFTR alternative translation. CONCLUSIONS: The CFTR N-terminus has an important role in avoiding CFTR turnover and in rendering effective its plasma membrane traffic. These data correlate well with the severe clinical phenotype of CF patients bearing the c.120del23 mutation.
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126 jointly mutated into valines and the respective stable cells wereanalysedbyimmunoblotforCFTR.ResultsinFig.5A reveal the presence of two proteins (D and E) for single mutants of M82V, M150V, M152V and M156V (lanes 36, respectively) and also for the double mutants M150V/ M152, M150V/M156V and M152V/M156V (lanes 7-9).
X
ABCC7 p.Met156Val 19910674:126:200
status: NEWX
ABCC7 p.Met156Val 19910674:126:282
status: NEWX
ABCC7 p.Met156Val 19910674:126:298
status: NEW140 Lanes 3-10 correspond to the proteins produced by the methionines mutants all in the c.120del23-CFTR pNUT background: lane 3, M82V; lane 4, M150V; lane 5 M152V; lane 6, M156V; lane 7, M150V/M152V; lane 8, M150V/M156V; lane 9, M152V/M156V; lane 10, M150V/M152V/M156V.
X
ABCC7 p.Met156Val 19910674:140:169
status: NEWX
ABCC7 p.Met156Val 19910674:140:211
status: NEWX
ABCC7 p.Met156Val 19910674:140:232
status: NEWX
ABCC7 p.Met156Val 19910674:140:260
status: NEW144 Lanes 2-8 all in pSP73: 2, CFTR exons 2-24; 3, M82V/ M150V/M152V/M156V; 4, M82V/M150V/M152V; 5, M82/M152V; 6, M82V/M150V;7, M150; 8, M82V.
X
ABCC7 p.Met156Val 19910674:144:65
status: NEW148 However, when the triple mutant (M150V/M152V/M156V) was analysed (lane 10, Fig.5A), only the lower form (E ~128 kDa) could be detected.
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ABCC7 p.Met156Val 19910674:148:45
status: NEW