Open Access Highly Accessed Research article

Classification of protein motifs based on subcellular localization uncovers evolutionary relationships at both sequence and functional levels

Marcos Parras-Moltó1, Francisco J Campos-Laborie1, Juan García-Diéguez1, M Rosario Rodríguez-Griñolo2 and Antonio J Pérez-Pulido1*

  • * Corresponding author: Antonio J Pérez-Pulido

  • † Equal contributors

Author Affiliations

1 Centro Andaluz de Biologia del Desarrollo (CABD, UPO-CSIC-JA). Facultad de Ciencias Experimentales (Área de Genética), Universidad Pablo de Olavide, 41013, Sevilla, Spain

2 Departamento de Economía, Métodos Cuantitativos e Historia Económica, Universidad Pablo de Olavide, 41013, Sevilla, Spain

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BMC Bioinformatics 2013, 14:229  doi:10.1186/1471-2105-14-229

Published: 18 July 2013



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.


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.


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.