Comparative genomic analysis of equilibrative nucleoside transporters suggests conserved protein structure despite limited sequence identity.
Equilibrative nucleoside transporters (ENTs) are a recently characterized and poorly understood group of membrane proteins that are important in the uptake of endogenous nucleosides required for nucleic acid and nucleoside triphosphate synthesis. Despite their central importance in cellular metabolism and nucleoside analog chemotherapy, no human ENT gene has been described and nothing is known about gene structure and function. To gain insight into the ENT gene family, we used experimental and in silico comparative genomic approaches to identify ENT genes in three evolutionarily diverse organisms with completely (or almost completely) sequenced genomes, Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster. We describe the chromosomal location, the predicted ENT gene structure and putative structural topologies of predicted ENT proteins derived from the open reading frames. Despite variations in genomic layout and limited ortholog protein sequence identity (< or =27.45%), predicted topologies of ENT proteins are strikingly similar, suggesting an evolutionary conservation of a prototypic structure. In addition, a similar distribution of protein domains on exons is apparent in all three taxa. These data demonstrate that comparative sequence analyses should be combined with other approaches (such as genomic and proteomic analyses) to fully understand structure, function and evolution of protein families.
Sankar
Narendra
N
Department of Biology, York University, 4700 Keele Street, Toronto M3J 1P3, Canada.
Machado
Jerry
J
Abdulla
Parween
P
Hilliker
Arthur J
AJ
Coe
Imogen R
IR
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002874:Chromosome Mapping; D004331:Drosophila melanogaster / Q000235:genetics; D033721:Equilibrative Nucleoside Transporter 1 / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D023281:Genomics; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid
D033721:Equilibrative Nucleoside Transporter 1; D026901:Membrane Transport Proteins