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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.<\/jats:p>","DOI":"10.1093\/nar\/gkaa1079","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T04:14:45Z","timestamp":1604376885000},"page":"D266-D273","source":"Crossref","is-referenced-by-count":521,"title":["CATH: increased structural coverage of functional space"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-9144","authenticated-orcid":false,"given":"Ian","family":"Sillitoe","sequence":"first","affiliation":[{"name":"Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6568-9035","authenticated-orcid":false,"given":"Nicola","family":"Bordin","sequence":"additional","affiliation":[{"name":"Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, 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London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla S M","family":"Pang","sequence":"additional","affiliation":[{"name":"Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurel","family":"Woodridge","sequence":"additional","affiliation":[{"name":"Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Rauer","sequence":"additional","affiliation":[{"name":"Institute of Structural and Molecular Biology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3324-5755","authenticated-orcid":false,"given":"Neeladri","family":"Sen","sequence":"additional","affiliation":[{"name":"Institute of Structural and Molecular Biology, University 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Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-2589","authenticated-orcid":false,"given":"Karel","family":"Berka","sequence":"additional","affiliation":[{"name":"Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palack\u00fd University Olomouc, Olomouc 771 46, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana\u00a0Huta\u0159ov\u00e1","family":"Varekova","sequence":"additional","affiliation":[{"name":"National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 602 00, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radka","family":"Svobodova","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic| National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno 602 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