ABCMdb

ABCC8 p.Gln1485His

ClinVar:	c.4454G>A , p.Gly1485Glu D , Likely pathogenic
Predicted by SNAP2:	A: D (75%), C: D (71%), D: D (80%), E: N (72%), F: D (80%), G: D (75%), H: D (75%), I: D (80%), K: D (85%), L: D (85%), M: D (66%), N: D (80%), P: D (85%), R: D (85%), S: D (71%), T: D (75%), V: D (80%), W: D (80%), Y: D (80%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Mutations in the linker domain of NBD2 of SUR inhi... EMBO J. 2002 Aug 15;21(16):4250-8. Matsuo M, Dabrowski M, Ueda K, Ashcroft FM
Mutations in the linker domain of NBD2 of SUR inhibit transduction but not nucleotide binding.
EMBO J. 2002 Aug 15;21(16):4250-8., [PMID:12169627]

Abstract [show]
ATP-sensitive potassium (K(ATP)) channels are composed of an ATP-binding cassette (ABC) protein (SUR1, SUR2A or SUR2B) and an inwardly rectifying K(+) channel (Kir6.1 or Kir6.2). Like other ABC proteins, the nucleotide binding domains (NBDs) of SUR contain a highly conserved "signature sequence" (the linker, LSGGQ) whose function is unclear. Mutation of the conserved serine to arginine in the linker of NBD1 (S1R) or NBD2 (S2R) did not alter the ability of ATP or ADP (100 microM) to displace 8-azido-[(32)P]ATP binding to SUR1, or abolish ATP hydrolysis at NBD2. We co-expressed Kir6.2 with wild-type or mutant SUR in Xenopus oocytes and recorded the resulting currents in inside-out macropatches. The S1R mutation in SUR1, SUR2A or SUR2B reduced K(ATP) current activation by 100 microM MgADP, whereas the S2R mutation in SUR1 or SUR2B (but not SUR2A) abolished MgADP activation completely. The linker mutations also reduced (S1R) or abolished (S2R) MgATP-dependent activation of Kir6.2-R50G co-expressed with SUR1 or SUR2B. These results suggest that the linker serines are not required for nucleotide binding but may be involved in transducing nucleotide binding into channel activation.

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Sentences [show]
No. Sentence Comment
171 Other mutations (G1484D, G1484R and Q1485H) within the NBD2 linker of SUR1 have also been reported to prevent MgADP activation of the KATP channel (Shyng et al., 1997). Login to comment