CATH FunFHMMer web server: protein functional annotations using functional family assignments

Abstract

The widening function annotation gap in protein databases and the increasing number and diversity of the proteins being sequenced presents new challenges to protein function prediction methods. Multidomain proteins complicate the protein sequence-structure-function relationship further as new combinations of domains can expand the functional repertoire, creating new proteins and functions. Here, we present the FunFHMMer web server, which provides Gene Ontology (GO) annotations for query protein sequences based on the functional classification of the domain-based CATH-Gene3D resource. Our server also provides valuable information for the prediction of functional sites. The predictive power of FunFHMMer has been validated on a set of 95 proteins where FunFHMMer performs better than BLAST, Pfam and CDD. Recent validation by an independent international competition ranks FunFHMMer as one of the top function prediction methods in predicting GO annotations for both the Biological Process and Molecular Function Ontology. The FunFHMMer web server is available at http://www.cathdb.info/search/by_funfhmmer.

Figure 1.

Workflow for the FunFHMMer web server pipeline.

Figure 2.

Precision-Recall graph showing the performance of FunFHMMer (shown in red) compared to BLAST (shown in blue), Pfam (shown in green) and CDD (shown in violet) on the benchmark dataset.

Figure 3.

Example FunFHMMer web server results. CATH superfamilies and FunFams (functional families) have been identified within the example UniProt protein sequence P0AD61 submitted to the FunFHMMer web server. Functional information can be retrieved through ‘GO Terms’ and ‘EC Terms’ buttons.