ABCC7 p.Leu408Ala
| Predicted by SNAP2: | A: D (53%), C: N (61%), D: D (66%), E: D (59%), F: N (87%), G: D (66%), H: D (53%), I: N (93%), K: D (63%), M: N (78%), N: D (59%), P: D (63%), Q: N (53%), R: D (63%), S: D (53%), T: N (61%), V: N (87%), W: N (53%), Y: N (57%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: 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.
[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.
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).
X
ABCC7 p.Leu408Ala 8548288:125:223
status: NEW124 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).
X
ABCC7 p.Leu408Ala 8548288:124:223
status: NEW