A cross-species analysis of the cystic fibrosis transmembrane conductance regulator: Potential functional domains and regulatory sites

Gill Diamond, Thomas F. Scanlin, Michael A. Zasloff, Charles L Bevins

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

To help elucidate the function of the cystic fibrosis transmembrane conductance regulator (CFTR), we have undertaken a cross-species analysis of the DNA sequence which encodes this protein. We have isolated and characterized the cDNA of the bovine homologue of CFTR. The deduced amino acid sequence shows high overall identity with the published sequences from human and mouse, although there is marked variability between the different potential functional domains. The region around human amino acid 508, which is deleted in 70% of cystic fibrosis chromosomes, is highly conserved across species; of the missense cystic fibrosis mutations reported to date, all of the amino acids in the normal human sequence are conserved in the bovine and mouse sequences. A single amino acid encoded by the human cDNA (Ser-434) is missing in the bovine sequence, and there are two amino acids encoded by the bovine sequence which are absent in the human. These all stem from in-frame 3-base omissions within the sequences. In addition to the cow, we amplified the DNA sequences encoding a portion of the R-domain from sheep, monkey, rabbit, and guinea pig. These sequences show relatively low overall sequence identity (63%), but nearly all of the potential protein kinase A and protein kinase C phosphorylation sites are conserved over all of the species examined. Our results suggest functional significance for certain highly conserved residues and putative domains within CFTR.

Original languageEnglish (US)
Pages (from-to)22761-22769
Number of pages9
JournalJournal of Biological Chemistry
Volume266
Issue number33
StatePublished - 1991
Externally publishedYes

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Cystic Fibrosis Transmembrane Conductance Regulator
Amino Acids
DNA sequences
Cystic Fibrosis
Amino Acid Sequence
Complementary DNA
Phosphorylation
Conserved Sequence
Chromosomes
Cyclic AMP-Dependent Protein Kinases
DNA Sequence Analysis
Protein Kinase C
Haplorhini
Sheep
Guinea Pigs
Rabbits
Mutation
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

A cross-species analysis of the cystic fibrosis transmembrane conductance regulator : Potential functional domains and regulatory sites. / Diamond, Gill; Scanlin, Thomas F.; Zasloff, Michael A.; Bevins, Charles L.

In: Journal of Biological Chemistry, Vol. 266, No. 33, 1991, p. 22761-22769.

Research output: Contribution to journalArticle

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abstract = "To help elucidate the function of the cystic fibrosis transmembrane conductance regulator (CFTR), we have undertaken a cross-species analysis of the DNA sequence which encodes this protein. We have isolated and characterized the cDNA of the bovine homologue of CFTR. The deduced amino acid sequence shows high overall identity with the published sequences from human and mouse, although there is marked variability between the different potential functional domains. The region around human amino acid 508, which is deleted in 70{\%} of cystic fibrosis chromosomes, is highly conserved across species; of the missense cystic fibrosis mutations reported to date, all of the amino acids in the normal human sequence are conserved in the bovine and mouse sequences. A single amino acid encoded by the human cDNA (Ser-434) is missing in the bovine sequence, and there are two amino acids encoded by the bovine sequence which are absent in the human. These all stem from in-frame 3-base omissions within the sequences. In addition to the cow, we amplified the DNA sequences encoding a portion of the R-domain from sheep, monkey, rabbit, and guinea pig. These sequences show relatively low overall sequence identity (63{\%}), but nearly all of the potential protein kinase A and protein kinase C phosphorylation sites are conserved over all of the species examined. Our results suggest functional significance for certain highly conserved residues and putative domains within CFTR.",
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