ABCC7 p.Ser795Glu
| Predicted by SNAP2: | A: D (53%), C: D (53%), D: N (53%), E: N (61%), F: D (63%), G: N (72%), H: D (53%), I: D (63%), K: N (61%), L: D (63%), M: D (53%), N: N (78%), P: N (66%), Q: N (53%), R: D (59%), T: N (78%), V: D (59%), W: D (71%), Y: D (66%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: N, N: N, P: N, Q: N, R: N, T: N, V: D, W: D, Y: D, |
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[hide] The non-hydrolytic pathway of cystic fibrosis tran... J Physiol. 2000 Oct 15;528 Pt 2:259-65. Aleksandrov AA, Chang X, Aleksandrov L, Riordan JR
The non-hydrolytic pathway of cystic fibrosis transmembrane conductance regulator ion channel gating.
J Physiol. 2000 Oct 15;528 Pt 2:259-65., 2000-10-15 [PMID:11034616]
Abstract [show]
It has been suggested that the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel may utilize a novel gating mechanism in which open and closed states are not in thermodynamic equilibrium. This suggestion is based on the assumption that energy of ATP hydrolysis drives the gating cycle. We demonstrate that CFTR channel gating occurs in the absence of ATP hydrolysis and hence does not depend on an input of free energy from this source. The binding of ATP or structurally related analogues that are poorly or non-hydrolysable is sufficient to induce opening. Closing occurs on dissociation of these ligands or the hydrolysis products of those that can be cleaved. Not only can channel opening occur without ATP hydrolysis but the temperature dependence of the open probability (Po.) is reversed, i.e. Po. increases as temperature is lowered whereas under hydrolytic conditions, Po. increases as temperature is elevated. This indicates that there are different rate-limiting steps in the alternate gating pathways (hydrolytic and non-hydrolytic). These observations demonstrate that phosphorylated CFTR behaves as a conventional ligand-gated channel employing cytoplasmic ATP as a readily available cytoplasmic ligand; under physiological conditions ligand hydrolysis provides efficient reversibility of channel opening.
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No. Sentence Comment
64 8SE construct The 8SE construct was made based on the 4SE mutant CFTR construct containing S660E, S737E, S795E and S813E (Chang et al. 1993).
X
ABCC7 p.Ser795Glu 11034616:64:105
status: NEW67 The DraIII fragment in the pNUT-4SE-CFTR was replaced by the DraIII fragment containing S660EÏS686EÏS700EÏS712EÏS737EÏS768E/S795E/S813E (8SE).
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ABCC7 p.Ser795Glu 11034616:67:149
status: NEW[hide] Protein kinase A (PKA) still activates CFTR chlori... J Biol Chem. 1993 May 25;268(15):11304-11. Chang XB, Tabcharani JA, Hou YX, Jensen TJ, Kartner N, Alon N, Hanrahan JW, Riordan JR
Protein kinase A (PKA) still activates CFTR chloride channel after mutagenesis of all 10 PKA consensus phosphorylation sites.
J Biol Chem. 1993 May 25;268(15):11304-11., [PMID:7684377]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) plays a central role in transepithelial ion transport by acting as a tightly regulated apical chloride channel. Regulation is achieved by the concerted action of ATP at conserved nucleotide binding folds and serine phosphorylation at multiple sites by protein kinases A (PKA) and C (PKC). A previous investigation concluded that activation by PKA is critically dependent on phosphorylation at four of the nine predicted PKA sites in the R domain (S660A, S737A, S795A, S813A), because a "Quad" mutant lacking these sites could not be activated. We show in the present work that not only can this mutant be phosphorylated and activated, but a mutant in which all 10 predicted PKA sites have been altered still retains significant PKA-activated function. Potentiation of the PKA response by PKC is also preserved in this mutant. Thus CFTR may be regulated by cryptic PKA sites which also mediate interactions between different kinases. Such hierarchical phosphorylation of CFTR by obvious and cryptic PKA sites could provide a metered response to secretagogues.
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No. Sentence Comment
37 The following mutations were introduced into CFTR, S422A (TCT to GCT), S660A (TCA to GCA), S686A (TCT to GCT), S700A (TCT toGCT), S712A (TCC to GCC), S737A (TCC to GCC), S768A (TCT toGCT), T788A (ACAto GCA),S795A (TCA to GCA), S813A (TCA to GCA), S660E (TCA to GAA),S737E (TCC to GAG), S795E (TCA to GAA), and S813E (TCA to GAA).
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ABCC7 p.Ser795Glu 7684377:37:286
status: NEW