Cystic Fibrosis Transmembrane Conductance Regulator Sequences: Comparative Analysis


Information obtained by comparing cystic fibrosis transmembrane conductance regulator sequences has been used to refine the domain structure of the protein, to better understand the effects of the many mutations identified in typical and atypical cystic fibrosis patients, and to develop better animal models for cystic fibrosis studies.

Keywords: cystic fibrosis transmembrane conductance regulator; disease model; domain structure; missense mutation; phylogeny

Figure 1.

The most parsimonious tree showing evolutionary relationships between CFTR sequences. The tree is obtained from a nucleotide sequence of 627 base pairs (bp) within CFTR exon 13 through a heuristic search of PAUP (Phylogenetic Analysis Using Parsimony; Swofford, ) using 1000 random addition sequences. Insertions/deletions provoked by teleostean sequences were removed because of ambiguous alignment, providing 541 positions, of which 340 are informative for parsimony. Tree length is 1249 with a consistency index of 0.60 and a retention index of 0.69. Branch length is given under ACCTRAN, and numbers at nodes are bootstrap proportions calculated from 1000 pseudoreplicates, given only when above 50%. The same tree was obtained from the neighbor‐joining method (data not shown). See Table for the sources of CFTR sequences.

Figure 2.

Global view of CFTRR domain structure and mutational pattern in the context of 21 aligned CFTR homologs (only full‐length sequences are included). The sequences are aligned by using Clustal W and checked by eye. Dashes indicate gaps that were introduced to maximize alignment. Bold letters show residues identical in all species. The top lines indicate NBD1 domain (solid line) and the R domain (dashed line) originally defined by Riordan et al.. The middle lines indicate the RD1 domain (solid line) and the RD2 domain (dashed line) defined by Dulhanty and Riordan . The lowest lines indicate the refined NBD1 domain (solid line) and the R domain (dashed line) defined by Chen et al., ). The grey shading indicates PKA consensus motifs that are phosphorylated only in vitro, and the black shading indicates those sites phosphorylated in vitro and in vivo. All of the currently identified missense mutations and single amino‐acid deletions are from the Cystic Fibrosis Mutation Database. See Table for the source of CFTR sequences. (See also Multiple Alignment.)



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Dulhanty AM and Riordan JR (1994) A two‐domain model for the R domain of the cystic fibrosis transmembrane conductance regulator based on sequence similarities. FEBS Letters 343: 109–114.

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Further Reading

Brown TA (1999) Genomes. Oxford, UK: BIOS Scientific.

Dean M, Rzhetsky A and Allikmets R (2001) The human ATP‐binding cassette (ABC) transporter superfamily. Genome Research 11: 1156–1166.

Gadsby DC and Nairn AC (1999) Control of CFTR channel gating by phosphorylation and nucleotide hydrolysis. Physiological Reviews 79: S77–S107.

Ko YH and Pedersen PL (2001) Cystic fibrosis: a brief look at some highlights of a decade of research focused on elucidating and correcting the molecular basis of the disease. Journal of Bioenergetics and Biomembranes 33: 513–521.

Ostedgaard LS, Baldursson O and Welsh MJ (2001) Regulation of the cystic fibrosis transmembrane conductance regulator Cl‐channel by its R domain. Journal of Biological Chemistry 276: 7689–7692.

Philippe H (1997) Rodent monophyly: pitfalls of molecular phylogenies. Journal of Molecular Evolution 45: 712–715.

Saitou N and Nei M (1987) The neighbor‐joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4: 406–425.

Sheppard DN and Welsh MJ (1999) Structure and function of the CFTR chloride channel. Physiological Reviews 79: S23–S45.

Welsh MJ, Ramsey BW, Accurso F and Cutting GR (2000) Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds.) The Metabolic and Molecular Bases of Inherited Disease, vol. 1, pp. 5121–5188. New York, NY: McGraw‐Hill.

Web Links

cystic fibrosis transmembrane conductance regulator, ATP‐binding cassette (CFTR); LocusID: 1080. LocusLink:

cystic fibrosis transmembrane conductance regulator, ATP‐binding cassette (CFTR); MIM number: 602421. OMIM:‐post/Omim/dispmim?602421

European Bioinformatics Institute. Links to databases of biological data, research, and research tools, including ClustalW

Cystic Fibrosis Mutation Data Base

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How to Cite close
Chen, Jian‐Min, Lecointre, Guillaume, Denamur, Erick, and Férec, Claude(Sep 2006) Cystic Fibrosis Transmembrane Conductance Regulator Sequences: Comparative Analysis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006227]