title: Functional classification of CATH superfamilies: a domain-based approach for protein function annotation.
abstract: BACKGROUND
  Computational approaches that can predict protein functions are essential to bridge the widening function annotation gap especially since <1.0% of all proteins in UniProtKB have been experimentally characterized. We present a domain-based method for protein function classification and prediction of functional sites that exploits functional sub-classification of CATH superfamilies. The superfamilies are sub-classified into functional families (FunFams) using a hierarchical clustering algorithm supervised by a new classification method, FunFHMMer.
  
  
  RESULTS
  FunFHMMer generates more functionally coherent groupings of protein sequences than other domain-based protein classifications. This has been validated using known functional information. The conserved positions predicted by the FunFams are also found to be enriched in known functional residues. Moreover, the functional annotations provided by the FunFams are found to be more precise than other domain-based resources. FunFHMMer currently identifies 110,439 FunFams in 2735 superfamilies which can be used to functionally annotate>16 million domain sequences.
  
  
  METHODS
  All FunFam annotation data are made available through the CATH webpages (http://www.cathdb.info). The FunFHMMer webserver (http://www.cathdb.info/search/by_funfhmmer) allows users to submit query sequences for assignment to a CATH FunFam.
  
  
  BACKGROUND
  sayoni.das.12@ucl.ac.uk
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: Sayoni
authors.initials: S
authors.lastname: Das
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Lee
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Sillitoe
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Dawson
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Lees
authors.affiliation: Institute of Structural and Molecular Biology, UCL, Darwin Building, Gower Street, WC1E 6BT, UK.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Orengo
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D030562:Databases, Protein; D006801:Humans; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D011506:Proteins