ABCMdb

ABCC7 p.Glu407Gln

ClinVar:	c.1220A>T , p.Glu407Val ? , not provided
CF databases:	c.1220A>T , p.Glu407Val (CFTR1) ? , The mutation was detected by multiplex heteroduplex analysis on the MDE gel matrix. It was found in one Canadian CF patient (second mutation: unknown).
Predicted by SNAP2:	A: N (78%), C: N (57%), D: N (87%), F: D (53%), G: D (59%), H: N (57%), I: N (53%), K: N (72%), L: N (53%), M: N (53%), N: N (82%), P: D (63%), Q: N (82%), R: D (59%), S: N (78%), T: N (61%), V: N (82%), W: D (53%), Y: D (53%),
Predicted by PROVEAN:	A: N, C: D, 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,

[switch to compact view]
Comments [show]

None has been submitted yet.

Publications
[hide] Identification and partial characterization of a d... Curr Biol. 1995 Oct 1;5(10):1159-67. Sullivan SK, Agellon LB, Schick R
Identification and partial characterization of a domain in CFTR that may bind cyclic nucleotides directly.
Curr Biol. 1995 Oct 1;5(10):1159-67., [PMID:8548288]

Abstract [show]
BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is activated by cAMP-dependent phosphorylation. CFTR channel activity is also stimulated by cGMP-dependent protein kinase and protein kinase C. RESULTS: Here, we show that CFTR channel activation by cGMP may also occur directly. In oocytes from one-third of Xenopus donors, the activation of CFTR by cGMP averaged 87% of the level achieved by cAMP. The currents activated by either cyclic nucleotide displayed similar current-voltage relationships, kinetics, pharmacology and halide selectivity. Sequential stimulation by cAMP and cGMP was not additive, suggesting that both cyclic nucleotides activate the same channel; cGMP was one order of magnitude more potent than cAMP, and its action was insensitive to protein kinase inhibitors. Analysis of the amino-acid sequence of CFTR revealed a domain in the amino-terminal portion of the third cytoplasmic loop that resembles a class of cyclic-nucleotide-binding domains related to that of the catabolite-gene activator protein, CAP. Two CFTR residues in this domain--Val397 and Lys420--were identified which, when changed to alanine, altered the response to cGMP independently of the response to cAMP. CONCLUSIONS: We conclude that direct cyclic nucleotide binding may play a role in channel gating of CFTR. The cGMP-binding domain may provide a useful target for pharmacologic intervention in cystic fibrosis.

Comments [show]

None has been submitted yet.

Sentences [show]
No. Sentence Comment
125 The current was only 18 + 13 % (n = 3) of wild-type level for the mutant channel with the glutamate at position 407 substituted by glutamine (mutant E407Q, using the single-letter amino-acid code); 16 + 3 % (n = 4) for the L408A mutant; and 17 ±+1 % (n = 4) for the T421A mutant (data not shown). Login to comment
127 A double substitution mutant (E407Q plus E403D) produced 63 + 8 % (n = 9) wild-type channel current (wild-type =2250 + 195 nA; n = 5; data not shown). Login to comment
124 The current was only 18 + 13 % (n = 3) of wild-type level for the mutant channel with the glutamate at position 407 substituted by glutamine (mutant E407Q, using the single-letter amino-acid code); 16 + 3 % (n = 4) for the L408A mutant; and 17 &#b1;+1 % (n = 4) for the T421A mutant (data not shown). Login to comment
126 A double substitution mutant (E407Q plus E403D) produced 63 + 8 % (n = 9) wild-type channel current (wild-type =2250 + 195 nA; n = 5; data not shown). Login to comment