ABCC7 p.Pro355Ser
| CF databases: |
c.1063C>T
,
p.Pro355Ser
(CFTR1)
?
, The mutation was detected by DGGE analysis and characterised by direct sequencing. We have seen it only once, in over 2500 control chromosomes from Italian population.
|
| Predicted by SNAP2: | A: D (63%), C: D (63%), D: D (75%), E: D (75%), F: D (80%), G: D (71%), H: D (63%), I: D (75%), K: D (85%), L: D (80%), M: D (71%), N: D (71%), Q: D (59%), R: D (75%), S: D (63%), T: D (71%), V: D (75%), W: D (80%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] A 10-year large-scale cystic fibrosis carrier scre... J Cyst Fibros. 2010 Jan;9(1):29-35. Epub 2009 Nov 7. Picci L, Cameran M, Marangon O, Marzenta D, Ferrari S, Frigo AC, Scarpa M
A 10-year large-scale cystic fibrosis carrier screening in the Italian population.
J Cyst Fibros. 2010 Jan;9(1):29-35. Epub 2009 Nov 7., [PMID:19897426]
Abstract [show]
BACKGROUND: Cystic Fibrosis (CF) is one of the most common autosomal recessive genetic disorders, with the majority of patients born to couples unaware of their carrier status. Carrier screenings might help reducing the incidence of CF. METHODS: We used a semi-automated reverse-dot blot assay identifying the 47 most common CFTR gene mutations followed by DGGE/dHPLC analysis. RESULTS: Results of a 10-year (1996-2006) CF carrier screening on 57,999 individuals with no prior family history of CF are reported. Of these, 25,104 were couples and 7791 singles, with 77.9% from the Italian Veneto region. CFTR mutations were found in 1879 carriers (frequency 1/31), with DeltaF508 being the most common (42.6%). Subjects undergoing medically assisted reproduction (MAR) had significantly (p<0.0001) higher CF carrier frequency (1/22 vs 1/32) compared to non-MAR subjects. CONCLUSIONS: If coupled to counselling programmes, CF carrier screening tests might help reducing the CF incidence.
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No. Sentence Comment
131 Aminoacid change Nucleotide change A349V 1178C→T D372E 1251T→G D674V 2153A→T D806G 2549A→G I586V 1888A→G I807V 2551A→G I840T 2651T→C L1335F 4135C→T L1414S 4373T→C L1480P 4571T→C M348T 1175T→C N416S 1379A→G P1290T 4000C→T P355S 1195C→T Q1268R 3935A→G Q1352E 4186C→G S431G 2423A→G S660T 2110T→A S911R 2865T→G T1263A 3919A→G T788I 2495C→T V920L 2890G→T Y1381H 4273T→C Y84H 382T→C two CFTR mutations and who had not been previously diagnosed with CF [29].
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ABCC7 p.Pro355Ser 19897426:131:312
status: NEW[hide] Conserved allosteric hot spots in the transmembran... J Biol Chem. 2014 Jul 18;289(29):19942-57. doi: 10.1074/jbc.M114.562116. Epub 2014 May 29. Wei S, Roessler BC, Chauvet S, Guo J, Hartman JL 4th, Kirk KL
Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.
J Biol Chem. 2014 Jul 18;289(29):19942-57. doi: 10.1074/jbc.M114.562116. Epub 2014 May 29., [PMID:24876383]
Abstract [show]
ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-beta,gamma-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs.
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158 Mean percentages of ATP-free currents afe; S.E. (error bars) were as follows: WT, 0.7 afe; 0.2% (n afd; 5); P355A, 5.0 afe; 1.4% (n afd; 10); P355S, 7.3 afe; 2.0% (n afd; 7); and P355F, 5.4 afe; 1.5% (n afd; 5).
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ABCC7 p.Pro355Ser 24876383:158:157
status: NEW165 TABLE 1 Single channel data for multiple Pro-355 CFTR mutants in the absence of ATP and following AMP-PNP activation Conditions were identical to those described in the legend to Fig. 2. n afd; 6 (WT), 7 (P355A), 8 (P355F), and 5 (P355S) patches, respectively.
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ABCC7 p.Pro355Ser 24876383:165:15
status: NEWX
ABCC7 p.Pro355Ser 24876383:165:234
status: NEW166 WT P355A P355F P355S Mean Po With ATP 0.3074afe;.00514 0.4078 afe; 0.0601 0.4867 afe; 0.0429 0.5212 afe; 0.1048 Without ATP 0.0009 afe; 0.0004 0.0217 afe; 0.0065a 0.0413 afe; 0.0145a 0.0365 afe; 0.0131a With AMP-PNP 0.0127 afe; 0.0114 0.1942 afe; 0.0619a 0.1112 afe; 0.0342a 0.1549 afe; 0.0651a Mean open frequency (sd1a;1 ) With ATP 0.222 afe; 0.021 0.270 afe; 0.028 0.384 afe; 0.049 0.334 afe; 0.059 Without ATP 0.004 afe; 0.001 0.020 afe; 0.002a 0.046 afe; 0.010a 0.028 afe; 0.006a With AMP-PNP 0.013 afe; 0.006 0.131 afe; 0.053a 0.104 afe; 0.035a 0.118 afe; 0.045a a p b0d; 0.05 compared with WT.
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ABCC7 p.Pro355Ser 24876383:166:15
status: NEW157 Mean percentages of ATP-free currents afe; S.E. (error bars) were as follows: WT, 0.7 afe; 0.2% (n afd; 5); P355A, 5.0 afe; 1.4% (n afd; 10); P355S, 7.3 afe; 2.0% (n afd; 7); and P355F, 5.4 afe; 1.5% (n afd; 5).
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ABCC7 p.Pro355Ser 24876383:157:157
status: NEW164 TABLE 1 Single channel data for multiple Pro-355 CFTR mutants in the absence of ATP and following AMP-PNP activation Conditions were identical to those described in the legend to Fig. 2. n afd; 6 (WT), 7 (P355A), 8 (P355F), and 5 (P355S) patches, respectively.
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ABCC7 p.Pro355Ser 24876383:164:234
status: NEW