CATH: increased structural coverage of functional space

Nucleic Acids Res. 2021 Jan 8;49(D1):D266-D273. doi: 10.1093/nar/gkaa1079.


CATH ( identifies domains in protein structures from wwPDB and classifies these into evolutionary superfamilies, thereby providing structural and functional annotations. There are two levels: CATH-B, a daily snapshot of the latest domain structures and superfamily assignments, and CATH+, with additional derived data, such as predicted sequence domains, and functionally coherent sequence subsets (Functional Families or FunFams). The latest CATH+ release, version 4.3, significantly increases coverage of structural and sequence data, with an addition of 65,351 fully-classified domains structures (+15%), providing 500 238 structural domains, and 151 million predicted sequence domains (+59%) assigned to 5481 superfamilies. The FunFam generation pipeline has been re-engineered to cope with the increased influx of data. Three times more sequences are captured in FunFams, with a concomitant increase in functional purity, information content and structural coverage. FunFam expansion increases the structural annotations provided for experimental GO terms (+59%). We also present CATH-FunVar web-pages displaying variations in protein sequences and their proximity to known or predicted functional sites. We present two case studies (1) putative cancer drivers and (2) SARS-CoV-2 proteins. Finally, we have improved links to and from CATH including SCOP, InterPro, Aquaria and 2DProt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • COVID-19 / epidemiology
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • Computational Biology / methods
  • Computational Biology / statistics & numerical data*
  • Databases, Protein / statistics & numerical data*
  • Epidemics
  • Humans
  • Internet
  • Molecular Sequence Annotation
  • Protein Domains*
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / metabolism
  • SARS-CoV-2 / physiology
  • Sequence Analysis, Protein / methods
  • Sequence Homology, Amino Acid
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Proteins
  • Viral Proteins