ABCC8 p.Ala1204Ser
| ClinVar: |
c.3612C>T
,
p.Ala1204=
N
, Benign
|
| Predicted by SNAP2: | C: N (53%), D: D (71%), E: D (63%), F: D (66%), G: N (57%), H: D (63%), I: D (63%), K: D (66%), L: D (66%), M: N (53%), N: N (93%), P: D (75%), Q: N (53%), R: D (66%), S: N (93%), T: N (93%), V: D (53%), W: D (71%), Y: D (66%), |
| Predicted by PROVEAN: | C: N, 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, S: N, T: N, V: D, W: D, Y: D, |
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[hide] Identification of the high-affinity tolbutamide si... Diabetes. 1999 Jun;48(6):1341-7. Ashfield R, Gribble FM, Ashcroft SJ, Ashcroft FM
Identification of the high-affinity tolbutamide site on the SUR1 subunit of the K(ATP) channel.
Diabetes. 1999 Jun;48(6):1341-7., [PMID:10342826]
Abstract [show]
ATP-sensitive potassium channels (K(ATP)) are formed from four pore-forming Kir6.2 subunits complexed with four regulatory sulfonylurea receptor subunits (SUR1 in pancreatic beta-cells, SUR2A in heart). The sensitivity of the channel to different sulfonylureas depends on the SUR isoform. In particular, Kir6.2-SUR1 but not Kir6.2-SUR2A channels are blocked by tolbutamide with high affinity. We made chimeras between SUR1 and SUR2A to identify the region of the protein involved in high-affinity tolbutamide block. Chimeric SURs were coexpressed with Kir6.2 in Xenopus oocytes, and macroscopic currents were measured in inside-out membrane patches. High-affinity tolbutamide inhibition could be conferred on SUR2A by replacing transmembrane domains (TMs) 14-16 with the corresponding region of SUR1. Conversely, high-affinity tolbutamide inhibition of SUR1 was abolished by replacing TMs 13-16 with the corresponding SUR2A sequence, or by mutating a single serine residue within this region to tyrosine (S1237Y). Binding of [3H]glibenclamide to membranes expressing SUR1 was abolished concomitantly with the loss of high-affinity tolbutamide block. These results suggest that a site in the COOH-terminal set of TMs of the SUR1 subunit of the K(ATP) channel is involved in the binding of tolbutamide and glibenclamide.
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No. Sentence Comment
127 Most mutations did not affect tolbutamide sensitivity: these included C1128T, T1130I, C1141S, C1174F, Q1190E, S1201C, A1204S, Y1218H, Q1223K, Y1229L, L1226M (data not shown; n = 2-4 patches in each case).
X
ABCC8 p.Ala1204Ser 10342826:127:118
status: NEW