ABCC7 p.Met1140Ile
| ClinVar: |
c.3419T>A
,
p.Met1140Lys
?
, not provided
|
| CF databases: |
c.3419T>A
,
p.Met1140Lys
(CFTR1)
?
, Found in a patient with bronchiectasis.
|
| Predicted by SNAP2: | A: D (85%), C: D (91%), D: D (95%), E: D (95%), F: D (91%), G: D (95%), H: D (95%), I: D (91%), K: D (95%), L: D (85%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (95%), T: D (91%), V: D (85%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: 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] 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.
Comments [show]
None has been submitted yet.
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).
X
ABCC7 p.Met1140Ile 9922378:249:257
status: NEW