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

Item Type:	Article
Title:	Enhanced function annotations for Drosophila serine proteases: a case study for systematic annotation of multi-member gene families
Creators Name:	Shah, P.K. and Tripathi, L.P. and Jensen, L.J. and Gahnim, M. and Mason, C. and Furlong, E.E. and Rodrigues, V. and White, K.P. and Bork, P. and Sowdhamini, R.
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.
Keywords:	Structural Properties, Immune Response, Evolution, Function Annotation, Gene-Expression Profiling, Enzyme Homologues, Drosophila Proteins, Drosophila Melanogaster, Animals, Insects
Source:	Gene
ISSN:	0378-1119
Publisher:	Elsevier
Volume:	407
Number:	1-2
Page Range:	199-215
Date:	15 January 2008
Official Publication:	https://doi.org/10.1016/j.gene.2007.10.012
PubMed:	View item in PubMed

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