CATH: increased structural coverage of functional space
Open accessAbstract
CATH (https://www.cathdb.info) 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.
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“A large fraction of training data, 46 ms, is dedicated to 1100 CATH domains, common building blocks of protein structure [33] (Sec.”
- Authors
- Sillitoe, I., Bordin, N., Dawson, N., Waman, V. P., Ashford, P., Scholes, H. M., Pang, C. S. M., Woodridge, L., Rauer, C., Sen, N., Abbasian, M., Le Cornu, S., Lam, S. D., Berka, K., Varekova, I. H., Svobodova, R., Lees, J., & Orengo, C. A.
- Affiliations
- Institute of Structural and Molecular Biology (GB)
- Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK
- National University of Malaysia (MY)
- Regional Centre of Advanced Technologies and Materials (CZ)
- National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 602 00, Czech Republic
- Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic| National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 602 00, Czech Republic
- Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK
- Corresponding author
- Sillitoe, Ian
- ORCID
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-11-25
- Volume
- 49
- Issue
- D1
- Pages
- D266-D273
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC7778904
- OpenAlex
- W3106745904
- Cited by
- 509
- References
- 25
- Citations by year
- 2026: 66 · 2025: 99 · 2024: 107 · 2023: 122 · 2022: 70 · 2021: 42 · 2020: 2
- FWCI
- 19.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Greater South Information System
- Funders
- BBSRC (BB/R009597/1, BB/S016007/1, BB/S020144/1, BB/T002735/1, BB/R014892/1, BB/S020039/1, BB/M009513/1)
- Wellcome Trust (104960/Z/14/Z, 203780/Z/16/A)
- Ministry of Education, Youth and Sports of the Czech Republic (LM2018131, CZ.02.1.01/0.0/0.0/16_013/0001777)
- Universiti Kebangsaan Malaysia (UKM-GGPM-2019-048)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- CATH, protein domain classification, protein superfamilies, functional annotation, protein structure annotation, SARS-CoV-2 proteins, SCOP, InterPro, aquariums
- MeSH terms
- Protein Domains, COVID-19, SARS-CoV-2, Amino Acid Sequence, Humans, Proteins, Viral Proteins, Sequence Homology, Amino Acid, Computational Biology, Internet, Sequence Analysis, Protein, Databases, Protein, Epidemics, Molecular Sequence Annotation
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