Prediction of potential GPI-modification sites in proprotein sequences.
Glycosylphosphatidylinositol (GPI) lipid anchoring is a common posttranslational modification known mainly from extracellular eukaryotic proteins. Attachment of the GPI moiety to the carboxyl terminus (omega-site) of the polypeptide follows after proteolytic cleavage of a C-terminal propeptide. For the first time, a new prediction technique locating potential GPI-modification sites in precursor sequences has been applied for large-scale protein sequence database searches. The composite prediction function (with separate parametrisation for metazoan and protozoan proteins) consists of terms evaluating both amino acid type preferences at sequence positions near a supposed omega-site as well as the concordance with general physical properties encoded in multi-residue correlation within the motif sequence. The latter terms are especially successful in rejecting non-appropriate sequences from consideration. The algorithm has been validated with a self-consistency and two jack-knife tests for the learning set of fully annotated sequences from the SWISS-PROT database as well as with a newly created database "big-Pi" (more than 300 GPI-motif mutations extracted from original literature sources). The accuracy of predicting the effect of mutations in the GPI sequence motif was above 83 %. Lists of potential precursor proteins which are non-annotated in SWISS-PROT and SPTrEMBL are presented on the WWW-page http://www.embl-heidelberg.de/beisenha/gpi/gpi_p rediction. html The algorithm has been implemented in the prototype software "big-Pi predictor" which may find application as a genome annotation and target selection tool.
Eisenhaber
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European Molecular Biology Laboratory, Meyerhofstrasse1, Heidelberg, D-69012, Federal Republic of Germany. b_eisen@nt.imp.univie.at
Bork
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Eisenhaber
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D000465:Algorithms; D002352:Carrier Proteins / Q000737:chemistry; D019992:Databases as Topic; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009154:Mutation; D020033:Protein Isoforms; D011498:Protein Precursors / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000737:chemistry; D011956:Receptors, Cell Surface; D017421:Sequence Analysis
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols; D008055:Lipids; D020033:Protein Isoforms; D011498:Protein Precursors; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface