ABCMdb

ABCC7 p.Asp924Ala

ClinVar:	c.2770G>A , p.Asp924Asn ? , not provided
CF databases:	c.2770G>A , p.Asp924Asn (CFTR1) ? , This substitution, located in a transmembrane domain, involves a residue conserved among species and affects the charge of the CFTR protein. It was found in the father of a fetus having hyperechogenic bowel. The man had a Polish origin. There was no family history of CF. The fetus inherited the mutation but no other anomaly was detected after scanning of almost all the CFTR coding regions and screening for 3849+10kbC->T and 1811+1.6kbA->G. The outcome of the pregnancy is still unknown. c.2770G>T , p.Asp924Tyr (CFTR1) ? ,
Predicted by SNAP2:	A: N (66%), C: N (53%), E: N (72%), F: D (66%), G: N (57%), H: D (71%), I: D (71%), K: D (66%), L: D (59%), M: D (66%), N: N (61%), P: D (75%), Q: D (63%), R: D (71%), S: N (66%), T: N (61%), V: D (63%), W: D (85%), Y: D (71%),
Predicted by PROVEAN:	A: N, C: N, E: 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: D, Y: N,

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Publications
[hide] Evidence for direct CFTR inhibition by CFTR(inh)-1... Biochem J. 2008 Jul 1;413(1):135-42. Caci E, Caputo A, Hinzpeter A, Arous N, Fanen P, Sonawane N, Verkman AS, Ravazzolo R, Zegarra-Moran O, Galietta LJ
Evidence for direct CFTR inhibition by CFTR(inh)-172 based on Arg347 mutagenesis.
Biochem J. 2008 Jul 1;413(1):135-42., 2008-07-01 [PMID:18366345]

Abstract [show]
CFTR (cystic fibrosis transmembrane conductance regulator) is an epithelial Cl- channel inhibited with high affinity and selectivity by the thiazolidinone compound CFTR(inh)-172. In the present study, we provide evidence that CFTR(inh)-172 acts directly on the CFTR. We introduced mutations in amino acid residues of the sixth transmembrane helix of the CFTR protein, a domain that has an important role in the formation of the channel pore. Basic and hydrophilic amino acids at positions 334-352 were replaced with alanine residues and the sensitivity to CFTR(inh)-172 was assessed using functional assays. We found that an arginine-to-alanine change at position 347 reduced the inhibitory potency of CFTR(inh)-172 by 20-30-fold. Mutagenesis of Arg347 to other amino acids also decreased the inhibitory potency, with aspartate producing near total loss of CFTR(inh)-172 activity. The results of the present study provide evidence that CFTR(inh)-172 interacts directly with CFTR, and that Arg347 is important for the interaction.

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Sentences [show]
No. Sentence Comment
134 Because Arg347 is believed to be involved in the formation of a salt bridge with Asp924 [25], we also tested the CFTR mutants D924A and D924R. Login to comment
145 In contrast with all other constructs, D924A and D924R did not show a significant I- transport compared with mock-transfected cells. Login to comment