Pathogenic mutation hotspots in protein kinase domain structure.
Protein Sci
; 32(9): e4750, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37572333
ABSTRACT
Control of eukaryotic cellular function is heavily reliant on the phosphorylation of proteins at specific amino acid residues, such as serine, threonine, tyrosine, and histidine. Protein kinases that are responsible for this process comprise one of the largest families of evolutionarily related proteins. Dysregulation of protein kinase signaling pathways is a frequent cause of a large variety of human diseases including cancer, autoimmune, neurodegenerative, and cardiovascular disorders. In this study, we mapped all pathogenic mutations in 497 human protein kinase domains from the ClinVar database to the reference structure of Aurora kinase A (AURKA) and grouped them by the relevance to the disease type. Our study revealed that the majority of mutation hotspots associated with cancer are situated within the catalytic and activation loops of the kinase domain, whereas non-cancer-related hotspots tend to be located outside of these regions. Additionally, we identified a hotspot at residue R371 of the AURKA structure that has the highest number of exclusively non-cancer-related pathogenic mutations (21) and has not been previously discussed.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Proteínas Serina-Treonina Quinases
Limite:
Humans
Idioma:
En
Revista:
Protein Sci
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos