Classification and Analysis of Eukaryotic ABC Transporters in Complete Eukarya Genomes

Abstract

We performed classification and analysis of the eukaryotic ABC (ATP-Binding Cassette) transporters in S. cerevisiae, C. elegans, and D. melanogaster which are the three eukarya whose genomes were sequenced completely. The ABC transporters form a major class of active transporters which are widespread in archaea, bacteria, and eukarya. These transporters convey a wide variety of substrates, such as peptides, amino acids, simple sugars, sulfate, phosphate and various drugs. The structure of a prokaryotic ABC transporter usually consists of three components. A typical transporter consists of two integral membrane proteins each having six transmembrane segments, two peripheral proteins that bind and hydrolyze ATP, and a periplasmic (or lipoprotein) substrate binding protein. Many of the genes for the three components form operons as in fact observed in known archaea and bacteria genomes On the other hand, in a typical eukaryotic ABC transporter, the membrane spanning protein and the ATP-binding protein are fused, forming a polypeptide with the membrane spanning domain and the ATP-binding domain. In prokaryotic ABC transporters, the ATP-binding protein component is the most conserved, the membrane protein component is somewhat less conserved, and the substrate-binding component is most divergent in terms of the sequence similarity (Tam and Saier 1993; Saurin and Dassa 1994). Therefore, in eukaryotic ABC transporters, it could also be expected that ATP-binding domain is the most conserved domain. In this analysis, we first searched and compared the eukaryotic ABC transporters in three eukarya complete sequenced genomes, S. cerevisiae, C.elegans and D.melangaster. Next, they were classified into orthologs and paralogs from sequence similarity and domain structure according to the hierarchical cluster analysis. Furthermore, hidden Markov models were built using individual clusters, and they were used to search for similar sequences in other genomes in the KEGG/GENES database.