A comprehensive classification system for transmembrane molecular transporters has been proposed. This system is based on (i) mode of transport and energy-coupling mechanism, (ii) protein phylogenetic family, (iii) phylogenetic cluster, and (iv) substrate specificity. The proposed "Transport Commission" (TC) system is superficially similar to that implemented decades ago by the Enzyme Commission for enzymes, but it differs from the latter system in that it uses phylogenetic and functional data for classification purposes. Very few families of transporters include members that do not function exclusively in transport. Analyses reported reveal that channels, primary carriers, secondary carriers (uni-, sym-, and antiporters), and group translocators comprise distinct categories of transporters, and that transport mode and energy coupling are relatively immutable characteristics. By contrast, substrate specificity and polarity of transport are often readily mutable. Thus, with very few exceptions, a unified family of transporters includes members that function by a single transport mode and energy-coupling mechanism although a variety of substrates may be transported with either inwardly or outwardly directed polarity. The TC system allows cross-referencing according to substrates transported and protein sequence database accession numbers. Thus, familial assignments of newly sequenced transport proteins are facilitated. In this article I examine families of transporters that are eukaryotic specific. These families include (i) channel proteins, mostly from animals; (ii) facilitators and secondary active transport carriers; (iii) a few ATP-dependent primary active transporters; and (iv) transporters of unknown mode of action or energy-coupling mechanism. None of the several ATP-independent primary active transport energy-coupling mechanisms found in prokaryotes is represented within the eukaryotic-specific families. The analyses reported provide insight into transporter families that may have arisen in eukaryotes after the separation of eukaryotes from archaea and bacteria. On the basis of the reported analyses, it is suggested that the horizontal transfer of genes encoding transport proteins between eukaryotes and members of the other two domains of life occurred very infrequently during evolutionary history.

• PMID: 10331239
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Journal Article | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, P.H.S. | Review

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Saier MH

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