ABCC7 p.Val1397Glu
| ClinVar: |
c.4190T>A
,
p.Val1397Glu
?
, not provided
|
| CF databases: |
c.4190T>A
,
p.Val1397Glu
(CFTR1)
?
, This mutation was identified by SSCP and direct sequencing. This was identified in a father of a deceased CF patient of Macedonian origin. This mutation was found once aomng 79 non-[delta]F508 CF chromosomes of Macedonian population.
|
| Predicted by SNAP2: | A: D (85%), C: D (71%), D: D (95%), E: D (59%), F: D (95%), G: D (95%), H: D (95%), I: D (75%), K: D (95%), L: D (95%), M: D (91%), N: D (95%), P: D (95%), Q: D (95%), R: D (95%), S: D (91%), T: D (85%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Aggregation of misfolded proteins can be a selecti... J Biol Chem. 2002 Sep 13;277(37):34462-70. Epub 2002 Jun 25. Milewski MI, Mickle JE, Forrest JK, Stanton BA, Cutting GR
Aggregation of misfolded proteins can be a selective process dependent upon peptide composition.
J Biol Chem. 2002 Sep 13;277(37):34462-70. Epub 2002 Jun 25., 2002-09-13 [PMID:12084728]
Abstract [show]
Intracellular aggregation of misfolded proteins is observed in a number of human diseases, in particular, neurologic disorders in which expanded tracts of polyglutamine residues play a central role. A variety of other proteins are prone to aggregation when mutated, indicating that this process is a common pathologic mechanism for inherited disorders. However, little is known about the relationship between the sequence of aggregating peptides and the specificity of intracellular accumulation. Here we demonstrate that substitution of two residues eliminates aggregation of a 111-amino acid peptide derived from the C-terminal portion of the cystic fibrosis transmembrane conductance regulator (CFTR). We also show that fusion to a reporter protein considerably alters the subcellular distribution of aggregating peptide. When fused to green fluorescent protein, the peptide containing amino acids 1370-1480 of CFTR accumulates in large perinuclear or nuclear aggregates. The same CFTR fragment devoid of green fluorescent protein localizes predominantly to discrete accumulations associated with mitochondria. Importantly, both types of accumulation are dependent on the presence of the same two amino acids within the CFTR sequence. Co-expression studies show that both CFTR-derived proteins can co-localize in large cytoplasmic/nuclear aggregates. However, neither CFTR construct accumulates in intracellular inclusions formed by N-terminal fragment of huntingtin. In addition to unique accumulation patterns, each aggregating peptide shows differences in association with chaperone proteins. Thus, our results indicate that the process of intracellular aggregation can be a selective process determined by the composition of the aggregating peptides.
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No. Sentence Comment
85 The only reported CF-causing mutation in the ag region was a substitution of valine at codon 1397 by glutamic acid (V1397E) (29).
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ABCC7 p.Val1397Glu 12084728:85:116
status: NEW108 B-E, the effect of different mutations within the ag region, including ⌬ag (B), V1397E (C), T1396A (D), and double mutation H1402A,R1403A (E) on the aggregation of C terminus of CFTR fused to GFP (shown in green) in transiently transfected human airway epithelial (IB3-1) cells.
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ABCC7 p.Val1397Glu 12084728:108:87
status: NEW[hide] Nucleotide binding domains of human CFTR: a struct... Cell Mol Life Sci. 2005 Sep;62(18):2112-23. Eudes R, Lehn P, Ferec C, Mornon JP, Callebaut I
Nucleotide binding domains of human CFTR: a structural classification of critical residues and disease-causing mutations.
Cell Mol Life Sci. 2005 Sep;62(18):2112-23., [PMID:16132229]
Abstract [show]
Defective function of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) causes CF, the most frequent lethal inherited disease among the Caucasian population. The structure of this chloride ion channel includes two nucleotide-binding domains (NBDs), whose ATPase activity controls channel gating. Recently, the experimental structures of mouse and human CFTR NBD1 and our model of the human CFTR NBD1/NBD2 heterodimer have provided new insights into specific structural features of the CFTR NBD dimer. In the present work, we provide a structural classification of CF-causing mutations which may complement the existing functional classification. Our analysis also identified amino acid residues which may play a critical role in interdomain interaction and are located at the NBD1-NBD2 interface or on the surface of the dimer. In particular, a cluster of aromatic amino acids, which includes F508 and straddles the two NBDs, might be directly involved in the interaction of the NBD1/NBD2 heterodimer with the channel-forming membrane-spanning domains.
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No. Sentence Comment
330 Hum. Genet. 93: 67-73 34 Jones C. T., McIntosh I., Keston M., Ferguson A. and Brock D. J. (1992) Three novel mutations in the cystic fibrosis gene detected by chemical cleavage: analysis of variant splicing and a nonsense mutation. Hum. Mol. Genet. 1: 11-17 35 Petreska L., Koceva S., Gordova-Muratovska A., Nestorov R. and Efremov G. D. (1994) Identification of two new mutations (711 +3A→G and V1397E) in CF chromosomes of Albanian and Macedonian origin.
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ABCC7 p.Val1397Glu 16132229:330:403
status: NEW[hide] Molecular basis of cystic fibrosis in the Republic... Clin Genet. 1998 Sep;54(3):203-9. Petreska L, Koceva S, Plaseska D, Chernick M, Gordova-Muratovska A, Fustic S, Nestorov R, Efremov GD
Molecular basis of cystic fibrosis in the Republic of Macedonia.
Clin Genet. 1998 Sep;54(3):203-9., [PMID:9788722]
Abstract [show]
Eighty-three cystic fibrosis (CF) patients and their families, belonging to various ethnic groups living in the Republic of Macedonia were studied for molecular defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and for the associated extragenic marker loci XV-2c and KM19. The DNA methodology used included characterization of CFTR mutations in 19 exons (and flanking sequences) of the gene and analysis of distribution of the XV-2c/KM19 haplotypes among normal (N) and CF chromosomes by polymerase chain reaction (PCR) amplification followed by dot blot hybridization, restriction digestion, single-strand conformational polymorphism, constant denaturing gel electrophoresis, denaturing gradient gel electrophoresis, and sequencing. We identified 58.4% (97/166) of the CF chromosomes. Nine different CFTR gene mutations, including three novel ones, were found. Eight known and one new CFTR intragene polymorphisms were also characterized. The haplotype analysis of the XV-2c/TaqI and KM19/PstI polymorphic loci have shown that haplotype C is the most frequently found haplotype among the non-deltaF508 CF chromosomes from Macedonia (36.5%). The results demonstrate the broad heterogeneity of CF origin in this part of the Balkan Peninsula.
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No. Sentence Comment
68 Two of them were found by SSCP: 711+3A +G mutation, found in two Albanian chromosomes associated with haplotype A, and V1397E mutation found in a Macedonian chromosome.
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ABCC7 p.Val1397Glu 9788722:68:119
status: NEW71 C (19Y V1397E (exon 23) (0.6) MK (0.9%) SSCP ND (31)' Total 97 (58.4) a MK, Macedonian; AL, Albanian; novel mutation identified during this study 205 al. Table .
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ABCC7 p.Val1397Glu 9788722:71:7
status: NEW72 Clinical feaiures of the CF patients from Macedonia Genotype Number of CF patients (%) PI PS Shwachman scorea Age of onset GI- (mmljl) NDb AF508/AF508 AF508/G542X AF508/N1303K AF508/711+3A-.G AF508/711+W+G AF508/621+lG+T AF508/621+1G+T AF508/1811+1G-*C AF508/457TAT-*G AF508/3849G+A G542X/3849G+A N1303K/ND V1397E/ND AF508/ND NDiND Total 26 (31.3) 5 (6.0) 2 (2.4) 2 (2.4) 2 (2.4) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 1 (1.2) 13 (15.7) 27 (32.5) 83 (100.0) 26 5 2 1 1 1 1 1 1 1 1 1 7 4 1 15 7 63 13 25-85 30-60 38 84 82 35 78 80 83 50 82 83 I 30-60 20-90 ~~~~~ 1-6 months 1 month 3 months 1 month 1 month 2 months 2.5 years 2 months 2 months 2 months 1 month 6 years 3 weeks Variable Vanable ~ ~ ~~~ 80-210 116-166 180-200 80 120 170 156 240 150 98 190 65 65 65-2300 2 65-130 (ps) 58-230 (PO 5 65-130 (PS) 7 a Shown is the most recent Shwachman score.
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ABCC7 p.Val1397Glu 9788722:72:307
status: NEW80 In two families the genotypes were N1303/unknownand V1397E/unknown.
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ABCC7 p.Val1397Glu 9788722:80:52
status: NEW101 The mutations 711 +3A+G, 1811+IG-tC and V1397E were described for the first time in the literature, and to our knowledge they have not been found outside Macedonia.
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ABCC7 p.Val1397Glu 9788722:101:40
status: NEW[hide] Efficient endocytosis of the cystic fibrosis trans... J Biol Chem. 1999 Feb 5;274(6):3602-9. Prince LS, Peter K, Hatton SR, Zaliauskiene L, Cotlin LF, Clancy JP, Marchase RB, Collawn JF
Efficient endocytosis of the cystic fibrosis transmembrane conductance regulator requires a tyrosine-based signal.
J Biol Chem. 1999 Feb 5;274(6):3602-9., 1999-02-05 [PMID:9920908]
Abstract [show]
We previously demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR) is rapidly endocytosed in epithelial cells (Prince, L. S., Workman, R. B., Jr., and Marchase, R. B. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 5192-5196). To determine the structural features of CFTR required for endocytosis, we prepared chimeric molecules consisting of the amino-terminal (residues 2-78) and carboxyl-terminal tail regions (residues 1391-1476) of CFTR, each fused to the transmembrane and extracellular domains of the transferrin receptor. Functional analysis of the CFTR-(2-78) and CFTR-(1391-1476) indicated that both chimeras were rapidly internalized. Deletion of residues 1440-1476 had no effect on chimera internalization. Mutations of potential internalization signals in both cytoplasmic domains reveal that only one mutation inhibits internalization, Y1424A. Using a surface biotinylation reaction, we also examined internalization rates of wild type and mutant CFTRs expressed in COS-7 cells. We found that both wild type and A1440X CFTR were rapidly internalized, whereas the Y1424A CFTR mutant, like the chimeric protein, had approximately 40% reduced internalization activity. Deletions in the amino-terminal tail region of CFTR resulted in defective trafficking of CFTR out of the endoplasmic reticulum to the cell surface, suggesting that an intact amino terminus is critical for biosynthesis. In summary, our results suggest that both tail regions of CFTR are sufficient to promote rapid internalization of a reporter molecule and that tyrosine 1424 is required for efficient CFTR endocytosis.
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No. Sentence Comment
196 For comparison, only one mutation in the carboxyl-terminal tail has been reported to result in CF, V1397E.
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ABCC7 p.Val1397Glu 9920908:196:99
status: NEW[hide] Identification of two new mutations (711 +3A-->G a... Hum Mol Genet. 1994 Jun;3(6):999-1000. Petreska L, Koceva S, Gordova-Muratovska A, Nestorov R, Efremov GD
Identification of two new mutations (711 +3A-->G and V1397E) in CF chromosomes of Albanian and Macedonian origin.
Hum Mol Genet. 1994 Jun;3(6):999-1000., [PMID:7524913]
Abstract [show]
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No. Sentence Comment
5 Here we report two new nucleotide substitutions of the CFTR gene, one in intron 5 (711+3A -G), and one in exon 23 (V1397E), named accordingly to the nucleotide assignment of the CFGAC (Personal comm., 1990).
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ABCC7 p.Val1397Glu 7524913:5:115
status: NEW17 V1397E.
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ABCC7 p.Val1397Glu 7524913:17:0
status: NEW26 Identification of 711+3A-G (A) and V1397E (B) mutations by direct sequencing of DNA.
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ABCC7 p.Val1397Glu 7524913:26:35
status: NEW