ABCMdb

ABCC7 p.Asp1270Val

ClinVar:	c.3808G>A , p.Asp1270Asn ? , Conflicting interpretations of pathogenicity, not provided c.3808G>T , p.Asp1270Tyr ? , not provided
CF databases:	c.3808G>A , p.Asp1270Asn ? , Varying clinical consequence ; CFTR1: The patient that carries the D1270N is an otherwise healthy male wth congenital absence of the vas deferens, an autosomal recessive disorder causing male aterility. The patient also carries an [delta]F508 mutation on the other chromosome. We did not find D1270N in iver 100 CF patients or in 91 fertile CF-carrier males. c.3808G>T , p.Asp1270Tyr (CFTR1) ? , This mutation was identified in two brother siblings with CF.
Predicted by SNAP2:	A: D (91%), C: D (85%), E: D (95%), F: D (95%), G: D (95%), H: D (95%), I: D (95%), K: D (95%), L: D (95%), M: D (95%), N: D (91%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%),
Predicted by PROVEAN:	A: D, C: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Localization of sequences within the C-terminal do... J Biol Chem. 2001 Jan 12;276(2):1291-8. Gentzsch M, Riordan JR
Localization of sequences within the C-terminal domain of the cystic fibrosis transmembrane conductance regulator which impact maturation and stability.
J Biol Chem. 2001 Jan 12;276(2):1291-8., 2001-01-12 [PMID:11022033]

Abstract [show]
Some disease-associated truncations within the 100-residue domain C-terminal of the second nucleotide-binding domain destabilize the mature protein (Haardt, M., Benharouga, M., Lechardeur, D., Kartner, N., and Lukacs, G. L. (1999) J. Biol. Chem. 274, 21873-21877). We now have identified three short oligopeptide regions in the C-terminal domain which impact cystic fibrosis transmembrane conductance regulator (CFTR) maturation and stability in different ways. A highly conserved hydrophobic patch (region I) formed by residues 1413-1416 (FLVI) was found to be crucial for the stability of the mature protein. Nascent chain stability was severely decreased by shortening the protein by 81 amino acids (1400X). This accelerated degradation was sensitive to proteasome inhibitors but not influenced by brefeldin A, indicating that it occurred at the endoplasmic reticulum. The five residues at positions 1400 to 1404 (region II) normally maintain nascent CFTR stability in a positional rather than a sequence-specific manner. A third modulating region (III) constituted by residues 1390 to 1394 destabilizes the protein. Hence the nascent form regains stability on further truncation back to residues 1390 or 1380, permitting some degree of maturation and a low level of cyclic AMP-stimulated chloride channel activity at the cell surface. Thus while not absolutely essential, the C-terminal domain strongly modulates the biogenesis and maturation of CFTR.

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Sentences [show]
No. Sentence Comment
36 The BprPI-ApaI fragment of the created plasmids was then used to replace the corresponding fragment of pNUT-D1270V CFTR. Login to comment
41 The BprPI-ApaI fragment of pBQ 4.7 M1475VCFTR and the derived mutated plasmids were used to replace the corresponding fragment of pNUT-D1270V CFTR. Login to comment