ABCC7 p.Asp924Gln
| ClinVar: |
c.2770G>A
,
p.Asp924Asn
?
, not provided
|
| CF databases: |
c.2770G>A
,
p.Asp924Asn
(CFTR1)
?
, This substitution, located in a transmembrane domain, involves a residue conserved among species and affects the charge of the CFTR protein. It was found in the father of a fetus having hyperechogenic bowel. The man had a Polish origin. There was no family history of CF. The fetus inherited the mutation but no other anomaly was detected after scanning of almost all the CFTR coding regions and screening for 3849+10kbC->T and 1811+1.6kbA->G. The outcome of the pregnancy is still unknown.
c.2770G>T , p.Asp924Tyr (CFTR1) ? , |
| Predicted by SNAP2: | A: N (66%), C: N (53%), E: N (72%), F: D (66%), G: N (57%), H: D (71%), I: D (71%), K: D (66%), L: D (59%), M: D (66%), N: N (61%), P: D (75%), Q: D (63%), R: D (71%), S: N (66%), T: N (61%), V: D (63%), W: D (85%), Y: D (71%), |
| Predicted by PROVEAN: | A: N, C: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] Sequence-specific retention and regulated integrat... Mol Biol Cell. 2009 Jan;20(2):685-98. Epub 2008 Nov 19. Pitonzo D, Yang Z, Matsumura Y, Johnson AE, Skach WR
Sequence-specific retention and regulated integration of a nascent membrane protein by the endoplasmic reticulum Sec61 translocon.
Mol Biol Cell. 2009 Jan;20(2):685-98. Epub 2008 Nov 19., [PMID:19019984]
Abstract [show]
A defining feature of eukaryotic polytopic protein biogenesis involves integration, folding, and packing of hydrophobic transmembrane (TM) segments into the apolar environment of the lipid bilayer. In the endoplasmic reticulum, this process is facilitated by the Sec61 translocon. Here, we use a photocross-linking approach to examine integration intermediates derived from the ATP-binding cassette transporter cystic fibrosis transmembrane conductance regulator (CFTR) and show that the timing of translocon-mediated integration can be regulated at specific stages of synthesis. During CFTR biogenesis, the eighth TM segment exits the ribosome and enters the translocon in proximity to Sec61alpha. This interaction is initially weak, and TM8 spontaneously dissociates from the translocon when the nascent chain is released from the ribosome. Polypeptide extension by only a few residues, however, results in stable TM8-Sec61alpha photocross-links that persist after peptidyl-tRNA bond cleavage. Retention of these untethered polypeptides within the translocon requires ribosome binding and is mediated by an acidic residue, Asp924, near the center of the putative TM8 helix. Remarkably, at this stage of synthesis, nascent chain release from the translocon is also strongly inhibited by ATP depletion. These findings contrast with passive partitioning models and indicate that Sec61alpha can retain TMs and actively inhibit membrane integration in a sequence-specific and ATP-dependent manner.
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No. Sentence Comment
250 (A) Photocross-linking to CFTR integration intermediates (residues 837-977) containing the -ANB-Lys probe at residue 913 in which Asp924 was mutated to glutamine (E), arginine (R), or valine (V).
X
ABCC7 p.Asp924Gln 19019984:250:138
status: NEW