ABCC7 p.Ser1426Ala
| ClinVar: |
c.4276T>C
,
p.Ser1426Pro
?
, not provided
|
| CF databases: |
c.4276T>C
,
p.Ser1426Pro
(CFTR1)
?
, This mutation was found in a patient with CBAVD.
c.4277C>T , p.Ser1426Phe (CFTR1) ? , This change has been detected by SSCP/HD analysis and direct sequencing. The mutation destroys a HinfI restriction site. |
| Predicted by SNAP2: | A: N (72%), C: N (57%), D: N (61%), E: N (87%), F: D (75%), G: N (72%), H: N (87%), I: N (57%), K: N (78%), L: N (53%), M: D (59%), N: N (93%), P: N (61%), Q: N (82%), R: N (66%), T: N (93%), V: N (66%), W: D (80%), Y: D (71%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: D, T: N, V: D, W: D, Y: D, |
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[hide] Inhibition of cystic fibrosis transmembrane conduc... J Clin Invest. 2000 Jun;105(12):1711-21. Hallows KR, Raghuram V, Kemp BE, Witters LA, Foskett JK
Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase.
J Clin Invest. 2000 Jun;105(12):1711-21., [PMID:10862786]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated Cl(-) channel that regulates other epithelial transport proteins by uncharacterized mechanisms. We employed a yeast two-hybrid screen using the COOH-terminal 70 residues of CFTR to identify proteins that might be involved in such interactions. The alpha1 (catalytic) subunit of AMP-activated protein kinase (AMPK) was identified as a dominant and novel interacting protein. The interaction is mediated by residues 1420-1457 in CFTR and by the COOH-terminal regulatory domain of alpha1-AMPK. Mutations of two protein trafficking motifs within the 38-amino acid region in CFTR each disrupted the interaction. GST-fusion protein pull-down assays in vitro and in transfected cells confirmed the CFTR-alpha1-AMPK interaction and also identified alpha2-AMPK as an interactor with CFTR. AMPK is coexpressed in CFTR-expressing cell lines and shares an apical distribution with CFTR in rat nasal epithelium. AMPK phosphorylated full-length CFTR in vitro, and AMPK coexpression with CFTR in Xenopus oocytes inhibited cAMP-activated CFTR whole-cell Cl(-) conductance by approximately 35-50%. Because AMPK is a metabolic sensor in cells and responds to changes in cellular ATP, regulation of CFTR by AMPK may be important in inhibiting CFTR under conditions of metabolic stress, thereby linking transepithelial transport to cell metabolic state.
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No. Sentence Comment
129 However, mutation of S1426 (S1426A and S1426D [not shown]) had no effect on the interaction strength. Mutation of Asp at 1445 to Asn (D1445N), a CF-causing mutation (Cystic Fibrosis Mutation Database at http://www.genet.sickkids.on.ca/cftr) also had no effect.
X
ABCC7 p.Ser1426Ala 10862786:129:28
status: NEW