The bestrophin family of anion channels: identification of prokaryotic homologues.
The human disease protein, Bestrophin-1, associated with vitelliform macular dystrophy, has recently been shown to be an integral membrane anion channel-forming protein. In this study we have recovered all bestrophin homologues from the NCBI database and analyzed their sequences using bioinformatic approaches. Eukaryotic homologues were found in animals and fungi but not in plants or protozoans, and prokaryotic homologues distantly related to the eukaryotic proteins, were identified in certain Gram-negative bacterial kingdoms but not in Gram-positive bacteria or archaea. Our analyses suggest a uniform 4 TMS topology for most of these homologues with regions of conservation overlapping and preceding the odd numbered TMSs and overlapping and following the even numbered TMSs. Well-conserved motifs were identified in both the eukaryotic and the prokaryotic homologues, and these proved to overlap, suggesting common structural and functional properties. Phylogenetic analyses revealed that the eukaryotic proteins cluster according to organismal type, and that the prokaryotic proteins sometimes (but not always) do so. This suggests that eukaryotic paralogues arose exclusively by recent gene duplication events although both early and late gene duplication events occurred in prokaryotes.
Hagen
Andrew R
AR
Division of Biological Sciences, University of California at San Diego, La Jolla, CA, 92093-0116, USA.
Barabote
Ravi D
RD
Saier
Milton H
MH
D000818:Animals; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015801:Helminth Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007473:Ion Channels; D005810:Multigene Family; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050994:Voltage-Dependent Anion Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
D019843:Archaeal Proteins; C113133:BEST1 protein, human; D001426:Bacterial Proteins; C491856:Best1 protein, mouse; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D005656:Fungal Proteins; D015801:Helminth Proteins; D007473:Ion Channels; D050994:Voltage-Dependent Anion Channels