ABCMdb

ABCC7 p.Glu217Arg

ClinVar:	c.650A>G , p.Glu217Gly D , Pathogenic
CF databases:	c.650A>G , p.Glu217Gly (CFTR1) ? , The mutation was detected by heteroduplex analysis in a 2-year old male Polish patient with high sweat cloride (60-80 meq/l), pancreatic sufficiency, and moderate lung disease. His other CF mutation is unknown. It was also found by Yoshimura in 1999, in the CFTR alleles of a single patient with diffuse panbronchiolitis who has Q1352 H in the other allele.
Predicted by SNAP2:	A: N (66%), C: D (59%), D: N (93%), F: D (80%), G: N (66%), H: N (53%), I: D (59%), K: N (72%), L: D (59%), M: D (53%), N: N (82%), P: D (59%), Q: N (66%), R: D (66%), S: N (66%), T: N (66%), V: D (53%), W: D (85%), Y: D (75%),
Predicted by PROVEAN:	A: N, C: D, D: N, F: D, G: N, H: N, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: N, T: N, V: D, W: D, Y: D,

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Publications
[hide] Topogenesis of cystic fibrosis transmembrane condu... Biochemistry. 1999 Apr 27;38(17):5471-7. Chen M, Zhang JT
Topogenesis of cystic fibrosis transmembrane conductance regulator (CFTR): regulation by the amino terminal transmembrane sequences.
Biochemistry. 1999 Apr 27;38(17):5471-7., 1999-04-27 [PMID:10220334]

Abstract [show]
Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transport superfamily. CFTR folding and assembly appear to involve several events occurred in the cytosol and ER. Misfolding of CFTR causes cystic fibrosis, and thus, understanding the folding mechanism of CFTR is extremely important. Recently, detailed study of membrane insertion process suggests that the first two transmembrane (TM) segments of CFTR have two distinct but independent mechanisms to ensure the correct membrane folding of its amino terminal end [Lu, Y., Xiong, X., Helm, A., Kimani, K., Bragin, A., Skach, W. R. (1998) J. Biol. Chem. 273, 568-576]. To understand how other TM segments are ensured to insert into membranes correctly, we investigated the topogenesis of TM3 and TM4 of CFTR in a cell-free expression system. We found that the correct membrane insertion of TM3 and TM4 of CFTR was ensured by their flanking amino acid sequences and controlled by the correct membrane insertion of their preceding TM1 and TM2. Thus, correct membrane insertion and folding of TM1 and TM2 play an essential role in the membrane insertion and folding of the subsequent TM segments of CFTR.

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Sentences [show]
No. Sentence Comment
47 Primers carrying various mutations are 5'-AATCTGGAGGTTGTTAAAGGCGTC-3' (E217R/Q220K), 5'-CATCATTTCCCCTAGCCC-3' (R242E), 5'-CT- GATCTTCGTAATTCATCATCAT-3' (K246N/R248E), and 5'-TCCCAGCTTCCTGATCT-3' (R251E). Login to comment
48 To make the CFTR-N4R(-8) and CFTR-N4R(-5) mutants, two PCR reactions were performed as described above using CFTR-N4R(E217R/Q220K) or wild-type CFTR-N4R as templates and the mutant primer 5'-AGGGGAAATGATGATGGAG- TACGAAGATCAGGAAGCTGGGGATATCAG-3'. Login to comment
49 The resulting constructs were named CFTR-N4R(E217R/Q220K), CFTR-N4R(R242E), CFTR-N4R(K246N/R248E), CFTR-N4R(R251E), CFTR-N4R(-8), and CFTR-N4R(-5). Login to comment
50 To remove TM1 and TM2 from CFTR-N4R, CFTR-N4R- (E217R/Q220K), CFTR-N4R(-8), and CFTR-N4R(-5), PCR was performed using a primer 5'-GAGACCATGCA- GATGAGAATAG-3' containing Kozak translation initiation codon and a primer 5'-CACTTTTGCCAACCAG-3' in the glycosylation reporter sequence on templates CFTR-N4R, CFTR-N4R(E217R/Q220K), CFTR-N4R(-8), and CFTR-N4R(-5), respectively. Login to comment
53 The final DNA clones were named CF-TM3,4R, CF-TM3,4R(E217R/Q220K), CF-TM3,4R(-8), and CF-TM3,4R(-5), respectively. To engineer R242E and K246N/R248E mutations into CF-TM3,4R, an EcoRI-EcoNI fragment encoding TM3 and part of TM4 was released from CF-TM3,4R and used to replace the amino terminal-encoding sequence in CFTR-N4R(R242E) and CFTR-N4R(K246N/R248E). Login to comment
72 The mutant molecules used were CF-TM3,4R(E217R/ Q220K), CF-TM3,4R(R242E), and CF-TM3,4R(K246N/ R248E). Login to comment