Prediction of potential GPI-modification sites in proprotein sequences

J Mol Biol. 1999 Sep 24;292(3):741-58. doi: 10.1006/jmbi.1999.3069.


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 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.

MeSH terms

  • Algorithms
  • Carrier Proteins / chemistry
  • Databases as Topic
  • Folate Receptors, GPI-Anchored
  • Glycosylphosphatidylinositols / chemistry*
  • Humans
  • Lipids / chemistry
  • Mutation
  • Protein Isoforms
  • Protein Precursors / chemistry*
  • Protein Processing, Post-Translational
  • Protozoan Proteins / chemistry
  • Receptors, Cell Surface*
  • Sequence Analysis


  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Glycosylphosphatidylinositols
  • Lipids
  • Protein Isoforms
  • Protein Precursors
  • Protozoan Proteins
  • Receptors, Cell Surface