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Signal Peptides 313
Recently, an objective assessment of signal peptide prediction methods was
undertaken using newly obtained data. 227 In short, von Heijne’s weight matrix method
was inferior to modern HMM or ANN methods, especially in correctly locating
cleavage sites, partly because it was handicapped with a very old dataset. The
accuracy of SignalP ver.2 and that of SignalP-HMM ver.2 were comparable, but the
latter was slightly superior in analysis of recently accumulated (and thus were not
used for training) data.
14.5.2 FROM PROTEOME TO SECRETOME
The last topic of this review is the comprehensive analysis of secreted proteins by
theoretical or experimental study. Such an analysis is often called secretome analysis.
158,228
Since the predictions of signal peptides and transmembrane regions are relatively
reliable, potential secreted proteins are detectable as proteins having a cleavable
signal peptide but not any other transmembrane segments. Several people have
attempted to estimate how many proteins are secreted in a proteome. 229 For example,
Schneider estimated ratios of secretory proteins coded in various genomes by using
an ANN method based on the amino acid composition of full-length sequence. 230
For bacteria living in mild conditions, the ratios ranged between 15 and 30%.
According to another analysis using TargetP, about 10% of Arabidopsis thaliana and
human genes were estimated to code secretory proteins. 219
Recently, prediction results of 180 secretory and 114 lipoprotein signal peptides
in B. subtilis were tested by a set of proteome experiments. 158,231 Surprisingly, the
authors concluded that the theoretical predictions reflect actual composition of the
extracellular proteins for about 50%. Note that this figure does not always mean the
direct prediction accuracy of current algorithms; one major reason was that many
proteins lacked apparent signal peptides; some cytoplasmic proteins and cell-bound
lipoproteins were also found in the extracellular medium. Perhaps “exceptional”
secretion pathway for these proteins exists like various secretion pathways of Gramnegative
bacteria. 186 In spite of difficulty of prediction, it is certain that these proteome
studies will provide invaluable data sources for improving the prediction
scheme.
At last, I would like to apologize to the many researchers whose important
references were not cited. In addition, I omitted several interesting topics including
various mutations on signal peptides and the fate of signal peptide fragments after
cleavage. 151,232,233
ACKNOWLEDGMENTS
I thank Koreaki Ito and his lab members for critically reading the manuscript. This
work was supported by Grant-in-Aid for Scientific Research on Priority Areas (C)
“Genome Information Science” from the Ministry of Education, Culture, Sports,
Science, and Technology of Japan.