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PreprintCited by 70Advanced Proteomics Techniques and ApplicationsBioinformatics and Genomic NetworksProtein Kinase Regulation and GTPase Signaling

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In vitro Kinase-to-Phosphosite database (iKiP-DB) predicts kinase activity in phosphoproteomic datasets

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Mari, Tommaso, Mösbauer, Kirstin, Wyler, Emanuel, Landthaler, Markus, Drosten, Christian, Selbach, Matthias·2022·Journal of Proteome Research
DOI 10.1101/2022.01.13.476159

Preprint — published as 10.1021/acs.jproteome.2c00198 · Paper page

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Abstract

Phosphoproteomics routinely quantifies changes in the levels of thousands of phosphorylation sites, but functional analysis of such data remains a major challenge. While databases like PhosphoSitePlus contain information about many phosphorylation sites, the vast majority of known sites are not assigned to any protein kinase. Assigning changes in the phosphoproteome to the activity of individual kinases therefore remains a key challenge.. A recent large-scale study systematically identified in vitro substrates for most human protein kinases. Here, we reprocessed and filtered these data to generate an in vitro Kinase-to-Phosphosite database (iKiP-DB). We show that iKiP-DB can accurately predict changes in kinase activity in published phosphoproteomic datasets for both well-studied and poorly characterized kinases. We apply iKiP-DB to a newly generated phosphoproteomic analysis of SARS-CoV-2 infected human lung epithelial cells and provide evidence for coronavirus-induced changes in host cell kinase activity. In summary, we show that iKiP-DB is widely applicable to facilitate the functional analysis of phosphoproteomic datasets.

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Metadata

Authors
Mari, T., Mösbauer, K., Wyler, E., Landthaler, M., Drosten, C., & Selbach, M.
Affiliations
  • Max Delbrück Center (DE)
  • Charité – Universitätsmedizin Berlin (DE)
Corresponding author
Selbach, Matthias
ORCID
Venue
Journal of Proteome Research
Publisher
openRxiv
Published
2022-01-14
Volume
21
Issue
6
Pages
1575-1587
ISSN
1535-3893 (ISSN-L)
DOI
10.1101/2022.01.13.476159
OpenAlex
W4282945860
Cited by
70
References
1
Citations by year
2026: 41 · 2025: 20 · 2024: 4 · 2023: 4 · 2022: 1
FWCI
2.62
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Proteome Research (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Bundesministerium für Bildung und Forschung (031L0220B)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
kinase substrates, phosphoproteomics, phosphorylation sites, SARS-CoV-2, lung epithelial cells, coronavirus infection
MeSH terms
COVID-19, SARS-CoV-2, Humans, Phosphoproteins, Phosphorylation, Protein Kinases

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