Research article

Prediction of disease-related mutations affecting protein localization

Kirsti Laurila^1,2 and Mauno Vihinen^1,3

¹  Institute of Medical Technology, FI-33014 University of Tampere, Finland

²  Department of Signal Processing, Tampere University of Technology, P.O. Box 527, FI-33101 Tampere, Finland

³  Tampere University Hospital, FI-33520 Tampere, Finland

author email corresponding author email

BMC Genomics 2009, 10:122doi:10.1186/1471-2164-10-122

Published:	23 March 2009

Abstract

Background

Eukaryotic cells contain numerous compartments, which have different protein constituents. Proteins are typically directed to compartments by short peptide sequences that act as targeting signals. Translocation to the proper compartment allows a protein to form the necessary interactions with its partners and take part in biological networks such as signalling and metabolic pathways. If a protein is not transported to the correct intracellular compartment either the reaction performed or information carried by the protein does not reach the proper site, causing either inactivation of central reactions or misregulation of signalling cascades, or the mislocalized active protein has harmful effects by acting in the wrong place.

Results

Numerous methods have been developed to predict protein subcellular localization with quite high accuracy. We applied bioinformatics methods to investigate the effects of known disease-related mutations on protein targeting and localization by analyzing over 22,000 missense mutations in more than 1,500 proteins with two complementary prediction approaches. Several hundred putative localization affecting mutations were identified and investigated statistically.

Conclusion

Although alterations to localization signals are rare, these effects should be taken into account when analyzing the consequences of disease-related mutations.