אסיף מאגר המחקר החקלאי

Enhanced function annotations for Drosophila serine proteases: A case study for systematic annotation of multi-member gene families

Year:

2008

Source of publication :

Authors :

Volume :

407

Co-Authors:

Shah, P.K., European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany, National Centre for Biological Sciences, TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India, Department of Human Genetics, The University of Chicago, Cummings Life Science Center, 920 E. 58th St., CLSC 301, Chicago, IL 60637, United States
Tripathi, L.P., National Centre for Biological Sciences, TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India
Jensen, L.J., European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Gahnim, M., Department of Human Genetics, The University of Chicago, Cummings Life Science Center, 920 E. 58th St., CLSC 301, Chicago, IL 60637, United States, Department of Entomology, Agricultural Research Organization, The Volcani Center, P.O.Box 6, Bet Dagan, 50250, Israel
Mason, C., Department of Human Genetics, The University of Chicago, Cummings Life Science Center, 920 E. 58th St., CLSC 301, Chicago, IL 60637, United States
Furlong, E.E., European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Rodrigues, V., Program on Neurogenetics, Yale University School of Medicine, New Haven, CT, United States, Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400 005, India
White, K.P., Department of Human Genetics, The University of Chicago, Cummings Life Science Center, 920 E. 58th St., CLSC 301, Chicago, IL 60637, United States
Bork, P., European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany
Sowdhamini, R., National Centre for Biological Sciences, TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India

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Abstract:

Systematically annotating function of enzymes that belong to large protein families encoded in a single eukaryotic genome is a very challenging task. We carried out such an exercise to annotate function for serine-protease family of the trypsin fold in Drosophila melanogaster, with an emphasis on annotating serine-protease homologues (SPHs) that may have lost their catalytic function. Our approach involves data mining and data integration to provide function annotations for 190 Drosophila gene products containing serine-protease-like domains, of which 35 are SPHs. This was accomplished by analysis of structure-function relationships, gene-expression profiles, large-scale protein-protein interaction data, literature mining and bioinformatic tools. We introduce functional residue clustering (FRC), a method that performs hierarchical clustering of sequences using properties of functionally important residues and utilizes correlation co-efficient as a quantitative similarity measure to transfer in vivo substrate specificities to proteases. We show that the efficiency of transfer of substrate-specificity information using this method is generally high. FRC was also applied on Drosophila proteases to assign putative competitive inhibitor relationships (CIRs). Microarray gene-expression data were utilized to uncover a large-scale and dual involvement of proteases in development and in immune response. We found specific recruitment of SPHs and proteases with CLIP domains in immune response, suggesting evolution of a new function for SPHs. We also suggest existence of separate downstream protease cascades for immune response against bacterial/fungal infections and parasite/parasitoid infections. We verify quality of our annotations using information from RNAi screens and other evidence types. Utilization of such multi-fold approaches results in 10-fold increase of function annotation for Drosophila serine proteases and demonstrates value in increasing annotations in multiple genomes. © 2007 Elsevier B.V. All rights reserved.

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