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.

The molecular mechanisms underlying lens fiber elongation

“…This observation is supported by the discovery that lens fibers express several common neuronal markers (Bitel et al, 2010; Frederikse et al, 2015). Since the prior studies on microtubules in lens fiber elongation during the 1970s, it has been demonstrated that elongating bundled microtubules at the tip of an axonal growth cone can provide the motile force to move cell plasma membranes forward to drive neuronal elongation while also regulating axonal pathfinding during neural development (Etienne-Manneville, 2013; Laan et al, 2008; Suter and Miller, 2011), even in the absence of motile forces provided by actin and myosin (Bradke and Dotti, 1999; Das et al, 2015; Dehmelt et al, 2006; Etienne-Manneville, 2013; Laan et al, 2008; Tanaka et al, 1995). Future studies might evaluate whether the interplay of microtubules and actin at the apical tip of an elongating fiber cell is structurally analogous to the neuronal growth cone.…”

Protein function annotation using protein domain family resources

“…The predictive power of the CATH FunFams have recently been evaluated using a rollback UniprotKB test set of 95 well-annotated proteins which had < 50% sequence identity to any experimentally annotated protein having GO molecular function ontology (MFO) terms [60].…”

“…The FunFHMMer web server is available at http://www.cathdb.info/search/by_funfhmmer [60]. The FunFHMMer web server can be queried using a protein sequence in the FASTA format or by entering UniProt/GenBank sequence identifiers as input in the text area on the webpage.…”

The Gene Ontology Handbook

“…GO terms are associated probabilistically to each functional family based on how often they occur in the UniProtKB annotations of the whole sequences. The recent CATH FunFHMMer web server automates the search procedure for input sequences, resolves multi-domain architectures, assigns each predicted domain to its functional family, and fi nally inherits the GO term annotations found in the library [ 61 ]. The dcGO-short for domain centric-method follows a similar route, but with some key differences [ 62 ].…”