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KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units

Adeyelu, Tolulope; Bordin, Nicola; Waman, Vaishali P; Sadlej, Marta; Sillitoe, Ian; Moya-Garcia, Aurelio A; Orengo, Christine A; (2023) KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units. Biomolecules , 13 (2) , Article 277. 10.3390/biom13020277. Green open access

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Abstract

Protein kinases are important targets for treating human disorders, and they are the second most targeted families after G-protein coupled receptors. Several resources provide classification of kinases into evolutionary families (based on sequence homology); however, very few systematically classify functional families (FunFams) comprising evolutionary relatives that share similar functional properties. We have developed the FunFam-MARC (Multidomain ARchitecture-based Clustering) protocol, which uses multi-domain architectures of protein kinases and specificity-determining residues for functional family classification. FunFam-MARC predicts 2210 kinase functional families (KinFams), which have increased functional coherence, in terms of EC annotations, compared to the widely used KinBase classification. Our protocol provides a comprehensive classification for kinase sequences from >10,000 organisms. We associate human KinFams with diseases and drugs and identify 28 druggable human KinFams, i.e., enriched in clinically approved drugs. Since relatives in the same druggable KinFam tend to be structurally conserved, including the drug-binding site, these KinFams may be valuable for shortlisting therapeutic targets. Information on the human KinFams and associated 3D structures from AlphaFold2 are provided via our CATH FTP website and Zenodo. This gives the domain structure representative of each KinFam together with information on any drug compounds available. For 32% of the KinFams, we provide information on highly conserved residue sites that may be associated with specificity.

Type: Article
Title: KinFams: De-Novo Classification of Protein Kinases Using CATH Functional Units
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/biom13020277
Publisher version: https://doi.org/10.3390/biom13020277
Language: English
Additional information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: protein kinases; functional families; KinFams; KinBase classification
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10165153
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