ABCC7 p.Thr1142Phe
| CF databases: |
c.3425C>T
,
p.Thr1142Ile
(CFTR1)
?
, This mutation was found by DGGE and direct DNA sequencing in asthamtic patients of age older than 60 years. Reported in Hum Mut 14:510-519(1999)
|
| Predicted by SNAP2: | A: D (63%), C: D (66%), D: D (85%), E: D (85%), F: D (80%), G: D (80%), H: D (85%), I: D (75%), K: D (91%), L: D (75%), M: D (63%), N: D (75%), P: D (85%), Q: D (80%), R: D (91%), S: N (53%), V: D (66%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: D, R: D, S: N, V: N, W: D, Y: D, |
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[hide] Pharmacology of CFTR chloride channel activity. Physiol Rev. 1999 Jan;79(1 Suppl):S109-44. Schultz BD, Singh AK, Devor DC, Bridges RJ
Pharmacology of CFTR chloride channel activity.
Physiol Rev. 1999 Jan;79(1 Suppl):S109-44., [PMID:9922378]
Abstract [show]
Pharmacology of CFTR Chloride Channel Activity. Physiol. Rev. 79, Suppl.: S109-S144, 1999. - The pharmacology of cystic fibrosis transmembrane conductance regulator (CFTR) is at an early stage of development. Here we attempt to review the status of those compounds that modulate the Cl- channel activity of CFTR. Three classes of compounds, the sulfonylureas, the disulfonic stilbenes, and the arylaminobenzoates, have been shown to directly interact with CFTR to cause channel blockade. Kinetic analysis has revealed the sulfonylureas and arylaminobenzoates interact with the open state of CFTR to cause blockade. Suggestive evidence indicates the disulfonic stilbenes act by a similar mechanism but only from the intracellular side of CFTR. Site-directed mutagenesis studies indicate the involvement of specific amino acid residues in the proposed transmembrane segment 6 for disulfonic stilbene blockade and segments 6 and 12 for arylaminobenzoate blockade. Unfortunately, these compounds (sulfonylureas, disulfonic stilbenes, arylaminobenzoate) also act at a number of other cellular sites that can indirectly alter the activity of CFTR or the transepithelial secretion of Cl-. The nonspecificity of these compounds has complicated the interpretation of results from cellular-based experiments. Compounds that increase the activity of CFTR include the alkylxanthines, phosphodiesterase inhibitors, phosphatase inhibitors, isoflavones and flavones, benzimidazolones, and psoralens. Channel activation can arise from the stimulation of the cAMP signal transduction cascade, the inhibition of inactivating enzymes (phosphodiesterases, phosphatases), as well as the direct binding to CFTR. However, in contrast to the compounds that block CFTR, a detailed understanding of how the above compounds increase the activity of CFTR has not yet emerged.
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No. Sentence Comment
249 The interpretation of ar- residues immediately adjacent to S341, DPC bound with an affinity close to that of the wild-type channel (S341A-ylaminobenzoate inhibition of macroscopic Cl0 secretion is, at best, difficult because of their nonselectivity for Cl0 M1140I-T1142F).
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ABCC7 p.Thr1142Phe 9922378:249:264
status: NEW[hide] Novel pore-lining residues in CFTR that govern per... Neuron. 1994 Sep;13(3):623-34. McDonough S, Davidson N, Lester HA, McCarty NA
Novel pore-lining residues in CFTR that govern permeation and open-channel block.
Neuron. 1994 Sep;13(3):623-34., [PMID:7522483]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) is both a member of the ATP-binding cassette superfamily and a Cl(-)-selective ion channel. We investigated the permeation pathway of human CFTR with measurements on conduction and open-channel blockade by diphenylamine-2-carboxylic acid (DPC). We used site-directed mutagenesis and oocyte expression to locate residues in transmembrane domain (TM) 6 and TM 12 that contact DPC and control rectification and single-channel conductances. Thus, TM 12 and the previously investigated TM 6 line the CFTR pore. In each TM, residues in contact with DPC are separated by two turns of an alpha helix. The contributions of TM 6 and TM 12 to DPC block and Cl- permeation, however, are not equivalent. The resulting structural model for the conduction pathway may guide future studies of permeation in other Cl- channels and ATP-binding cassette transporters.
Comments [show]
None has been submitted yet.
No. Sentence Comment
74 That is, the triple mutant S341A-M11401-T1142F bound DPC more tightly than S341A alone, with an affinity close to that of the wild-type channel (Figure 3D; Figure 4).
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ABCC7 p.Thr1142Phe 7522483:74:40
status: NEW84 E,,,, the reversal potential, determined empirically from the voltage steps; Triple, S341A-M11401-T1142F mutant.
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ABCC7 p.Thr1142Phe 7522483:84:98
status: NEW111 Open circles, wild-type; closed circles, T1134F; open boxes, S341A; closed boxes, triple mutation (S341A-Mll- 401-T1142F).
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ABCC7 p.Thr1142Phe 7522483:111:114
status: NEW158 The sequence M11401-S1141-T1142F in TM 12 restores DPC binding to the S341A mutant.
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ABCC7 p.Thr1142Phe 7522483:158:26
status: NEW