title: Prediction of disease-related mutations affecting protein localization.
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.
  
  
  CONCLUSIONS
  Although alterations to localization signals are rare, these effects should be taken into account when analyzing the consequences of disease-related mutations.
authors.affiliation: Institute of Medical Technology, University of Tampere, Tampere, Finland. kirsti.laurila@uta.fi
authors.forename: Kirsti
authors.initials: K
authors.lastname: Laurila
authors.forename: Mauno
authors.initials: M
authors.lastname: Vihinen
mesh_terms: D019295:Computational Biology / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D011506:Proteins