ArticleScientific reports2018
Integrative annotation and knowledge discovery of kinase post-translational modifications and cancer-associated mutations through federated protein ontologies and resources.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Leveraging AI to explore structural contexts of post-translational modifications in drug binding.Journal of cheminformatics · 2025Article
- Leveraging AI to Explore Structural Contexts of Post-Translational Modifications in Drug Binding.bioRxiv : the preprint server for biology · 2025Article
- Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.SLAS discovery : advancing life sciences R & D · 2024Article
- Cancer-associated mutations in protein kinase C theta are loss-of-function.The Biochemical journal · 2024Article
- c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.Genes & genomics · 2023Article
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- Identification of Activating Mutations in the Transmembrane and Extracellular Domains of EGFR.Biochemistry · 2022Article
- Protein kinase C: release from quarantine by mTORC2.Trends in biochemical sciences · 2022Review
- Phosphosite-dependent presentation of dual phosphorylated peptides by MHC class I molecules.iScience · 2022Article
- KinOrtho: a method for mapping human kinase orthologs across the tree of life and illuminating understudied kinases.BMC bioinformatics · 2021Article
- mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif.Science signaling · 2021Article
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- PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling.Annual review of pharmacology and toxicology · 2021Review
- Article
- Ten tips for a text-mining-ready article: How to improve automated discoverability and interpretability.PLoS biology · 2020Article
- PTMsnp: A Web Server for the Identification of Driver Mutations That Affect Protein Post-translational Modification.Frontiers in cell and developmental biology · 2020Article
- PubTator central: automated concept annotation for biomedical full text articles.Nucleic acids research · 2019Article
- Dynamics of Dual Specificity Phosphatases and Their Interplay with Protein Kinases in Immune Signaling.International journal of molecular sciences · 2019Article
- Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer.Molecular cell · 2019Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Many bioinformatics resources with unique perspectives on the protein landscape are currently available. However, generating new knowledge from these resources requires interoperable workflows that support cross-resource queries. In this study, we employ federated queries linking information from the Protein Kinase Ontology, iPTMnet, Protein Ontology, neXtProt, and the Mouse Genome Informatics to identify key knowledge gaps in the functional coverage of the human kinome and prioritize understudied kinases, cancer variants and post-translational modifications (PTMs) for functional studies. We identify 32 functional domains enriched in cancer variants and PTMs and generate mechanistic hypotheses on overlapping variant and PTM sites by aggregating information at the residue, protein, pathway and species level from these resources. We experimentally test the hypothesis that S768 phosphorylation in the C-helix of EGFR is inhibitory by showing that oncogenic variants altering S768 phosphorylation increase basal EGFR activity. In contrast, oncogenic variants altering conserved phosphorylation sites in the 'hydrophobic motif' of PKCβII (S660F and S660C) are loss-of-function in that they reduce kinase activity and enhance membrane translocation. Our studies provide a framework for integrative, consistent, and reproducible annotation of the cancer kinomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.