Abstract
BackgroundMembrane transporters catalyze the transport of small solute molecules across biological barriers such as lipid bilayer membranes. Experimental identification of the transported substrates is very tedious. Once a particular transport mechanism has been identified in one organism, it is thus highly desirable to transfer this information to related transporter sequences in different organisms based on bioinformatics evidence.ResultsWe present a thorough benchmark at which level of sequence identity membrane transporters from Escherichia coli, Saccharomyces cerevisiae, and Arabidopsis thaliana belong to the same families of the Transporter Classification (TC) system, and at what level these membrane transporters mediate the transport of the same substrate. We found that two membrane transporter sequences from different organisms that are aligned with normalized BLAST expectation value better than E-value 1e-8 are highly likely to belong to the same TC family (F-measure around 90%). Enriched sequence motifs identified by MEME at thresholds below 1e-12 support accurate classification into TC families for about two thirds of the sequences (F-measure 80% and higher). For the comparison of transported substrates, we focused on the four largest substrate classes of amino acids, sugars, metal ions, and phosphate. At similar identity thresholds, the nature of the transported substrates was more divergent (F-measure 40 - 75% at the same thresholds) than the TC family membership.ConclusionsWe suggest an acceptable threshold of 1e-8 for BLAST and HMMER where at least three quarters of the sequences are classified according to the TC system with a reasonably high accuracy. Researchers who wish to apply these thresholds in their studies should multiply these thresholds by the size of the database they search against. Our findings should be useful to those who wish to transfer transporter functional annotations across species.
Highlights
Membrane transporters catalyze the transport of small solute molecules across biological barriers such as lipid bilayer membranes
Our aim is to provide a simple guideline to biologists who wish to get a quick information whether available functional information about a transporter in species X may be transferred to another transporter sequence identified e.g. by BLAST search in species Y
Saccharomyces cerevisiae (Sc) contains twice as many metal ion transporters as Escherichia coli (Ec) and Arabidopsis thaliana (At) [22]. This can possibly be related with the existence of metallothionein proteins in yeast that function as a metal storage [23]
Summary
Membrane transporters catalyze the transport of small solute molecules across biological barriers such as lipid bilayer membranes. The available experimental knowledge about transporter function has been compiled in databases such as TCDB [1], TransportDB [2], SGD [3], and Aramemnon [4]. The TC system categorizes transporter sequences according to their class, subclass, (super) family, and subfamily on the basis of functional or phylogenetic information that is based on sequence similarity. An example for this classification would be the PTS Glucose-Glucoside (Glc) super family 4.A.1 that belongs to class ‘4’ group translocators and subclass ‘A’ phosphate transfer-driven group translocators. A particular transporter sequence in such a family is identified by an extra digit to the right as e.g. 4.A.1.1.1
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