Allergens are distributed into few protein families and possess a restricted number of biochemical functions

Background: Existing allergen databases classify their entries by source and route of exposure, thus lacking an evolutionary, structural, and functional classification of allergens. Objective: We sought to build AllFam, a database of allergen families, and use it to extract common structural and functional properties of allergens. Methods: Allergen data from the Allergome database and protein family definitions from the Pfam database were merged into AllFam, a database that is freely accessible on the Internet at: http://www.meduniwien.ac.at/allergens/allfam/. A structural classification of allergens was established by matching Pfam families with families from the Structural Classification of Proteins database. Biochemical functions of allergens were extracted from the Gene Ontology Annotation database. Results: Seven hundred seven allergens were classified by sequence into 134 AllFam families containing 184 Pfam domains (2% of 9318 Pfam families). A random set of 707 sequences with the same taxonomic distribution contained a significantly higher number of different Pfam domains (479 +/- 17). Classifying allergens by structure revealed that 5% of 3012 Structural Classification of Proteins families contained allergens. The biochemical functions of allergens most frequently found were limited to hydrolysis of proteins, polysaccharides, and lipids; binding of metal ions and lipids; storage; and cytoskeleton association. Conclusion: The small number of protein families that contain allergens and the narrow functional distribution of most allergens confirm the existence of yet unknown factors that render proteins allergenic.