FunTree: advances in a resource for exploring and contextualising protein function evolution

Nucleic Acids Res. 2016 Jan 4;44(D1):D317-23. doi: 10.1093/nar/gkv1274. Epub 2015 Nov 20.


FunTree is a resource that brings together protein sequence, structure and functional information, including overall chemical reaction and mechanistic data, for structurally defined domain superfamilies. Developed in tandem with the CATH database, the original FunTree contained just 276 superfamilies focused on enzymes. Here, we present an update of FunTree that has expanded to include 2340 superfamilies including both enzymes and proteins with non-enzymatic functions annotated by Gene Ontology (GO) terms. This allows the investigation of how novel functions have evolved within a structurally defined superfamily and provides a means to analyse trends across many superfamilies. This is done not only within the context of a protein's sequence and structure but also the relationships of their functions. New measures of functional similarity have been integrated, including for enzymes comparisons of overall reactions based on overall bond changes, reaction centres (the local environment atoms involved in the reaction) and the sub-structure similarities of the metabolites involved in the reaction and for non-enzymes semantic similarities based on the GO. To identify and highlight changes in function through evolution, ancestral character estimations are made and presented. All this is accessible through a new re-designed web interface that can be found at

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein*
  • Enzymes / chemistry
  • Enzymes / metabolism
  • Evolution, Molecular*
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / classification
  • Proteins / physiology*
  • Sequence Analysis, Protein


  • Enzymes
  • Proteins