title: Classification of protein motifs based on subcellular localization uncovers evolutionary relationships at both sequence and functional levels.
abstract: BACKGROUND
  Most proteins have evolved in specific cellular compartments that limit their functions and potential interactions. On the other hand, motifs define amino acid arrangements conserved between protein family members and represent powerful tools for assigning function to protein sequences. The ideal motif would identify all members of a protein family but in practice many motifs identify both family members and unrelated proteins, referred to as True Positive (TP) and False Positive (FP) sequences, respectively.
  
  
  RESULTS
  To address the relationship between protein motifs, protein function and cellular localization, we systematically assigned subcellular localization data to motif sequences from the comprehensive PROSITE sequence motif database. Using this data we analyzed relationships between localization and function. We find that TPs and FPs have a strong tendency to localize in different compartments. When multiple localizations are considered, TPs are usually distributed between related cellular compartments. We also identified cases where FPs are concentrated in particular subcellular regions, indicating possible functional or evolutionary relationships with TP sequences of the same motif.
  
  
  CONCLUSIONS
  Our findings suggest that the systematic examination of subcellular localization has the potential to uncover evolutionary and functional relationships between motif-containing sequences. We believe that this type of analysis complements existing motif annotations and could aid in their interpretation. Our results shed light on the evolution of cellular organelles and potentially establish the basis for new subcellular localization and function prediction algorithms.
authors.affiliation: Centro Andaluz de Biologia del Desarrollo (CABD, UPO-CSIC-JA), Facultad de Ciencias Experimentales (Área de Genética), Universidad Pablo de Olavide, 41013, Sevilla, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Parras-Moltó
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Campos-Laborie
authors.forename: Juan
authors.initials: J
authors.lastname: García-Diéguez
authors.forename: M Rosario
authors.initials: MR
authors.lastname: Rodríguez-Griñolo
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pérez-Pulido
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D019143:Evolution, Molecular; D005810:Multigene Family; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification / Q000502:physiology*
chemical_list: D011506:Proteins