Sahni, N. et al. Widespread macromolecular interaction perturbations in human genetic disorders. Cell 161, 647–660 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Woodsmith, J. & Stelzl, U. Studying post-translational modifications with protein interaction networks. Curr. Opin. Struct. Biol. 24, 34–44 (2014).

Article  PubMed  Google Scholar 

Iqbal, S. et al. Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants. Proc. Natl Acad. Sci. USA 117, 28201–28211 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Ardito, F., Giuliani, M., Perrone, D., Troiano, G. & Lo Muzio, L. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (review). Int. J. Mol. Med. 40, 271–280 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Viéitez, C. et al. High-throughput functional characterization of protein phosphorylation sites in yeast. Nat. Biotechnol. 40, 382–390 (2022).

Article  PubMed  Google Scholar 

Bowden, A. R. et al. Parallel CRISPR–Cas9 screens clarify impacts of p53 on screen performance. eLife 9, e55325 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Haapaniemi, E., Botla, S., Persson, J., Schmierer, B. & Taipale, J. CRISPR–Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med. 24, 927–930 (2018).

Article  PubMed  Google Scholar 

Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Cuella-Martin, R. et al. Functional interrogation of DNA damage response variants with base editing screens. Cell 184, 1081–1097 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Hanna, R. E. et al. Massively parallel assessment of human variants with base editor screens. Cell 184, 1064–1080 (2021).

Article  PubMed  Google Scholar 

Xu, P. et al. Genome-wide interrogation of gene functions through base editor screens empowered by barcoded sgRNAs. Nat. Biotechnol. 39, 1403–1413 (2021).

Article  PubMed  Google Scholar 

Koblan, L. W. et al. Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction. Nat. Biotechnol. 36, 843–846 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Zhu, S. et al. Guide RNAs with embedded barcodes boost CRISPR-pooled screens. Genome Biol. 20, 20 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Bao, Y. et al. Unbiased interrogation of functional lysine residues in human proteome. Mol. Cell 83, 4614–4632 (2023).

Article  PubMed  Google Scholar 

Kolde, R., Laur, S., Adler, P. & Vilo, J. Robust rank aggregation for gene list integration and meta-analysis. Bioinformatics 28, 573–580 (2012).

Article  PubMed  PubMed Central  Google Scholar 

Martinez-Jimenez, F. et al. A compendium of mutational cancer driver genes. Nat. Rev. Cancer 20, 555–572 (2020).

Article  PubMed  Google Scholar 

Kano, Y. et al. Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation. Nat. Commun. 10, 224 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Cirstea, I. C. et al. Diverging gain-of-function mechanisms of two novel KRAS mutations associated with Noonan and cardio-facio-cutaneous syndromes. Hum. Mol. Genet. 22, 262–270 (2013).

Article  PubMed  Google Scholar 

Gong, J. et al. The C2 domain and altered ATP-binding loop phosphorylation at Ser359 mediate the redox-dependent increase in protein kinase C-δ activity. Mol. Cell. Biol. 35, 1727–1740 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Newton, A. C. & Brognard, J. Reversing the paradigm: protein kinase C as a tumor suppressor. Trends Pharmacol. Sci. 38, 438–447 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Gilbert, L. A. et al. Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159, 647–661 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Dumaz, N. & Marais, R. Protein kinase A blocks Raf-1 activity by stimulating 14-3-3 binding and blocking Raf-1 interaction with Ras. J. Biol. Chem. 278, 29819–29823 (2003).

Article  PubMed  Google Scholar 

Grethe, S. & Porn-Ares, M. I. p38 MAPK regulates phosphorylation of Bad via PP2A-dependent suppression of the MEK1/2–ERK1/2 survival pathway in TNF-α induced endothelial apoptosis. Cell Signal 18, 531–540 (2006).

Article  PubMed  Google Scholar 

Lavoie, H., Gagnon, J. & Therrien, M. ERK signalling: a master regulator of cell behaviour, life and fate. Nat. Rev. Mol. Cell Biol. 21, 607–632 (2020).

Article  PubMed  Google Scholar 

Ochoa, D. et al. The functional landscape of the human phosphoproteome. Nat. Biotechnol. 38, 365–373 (2020).

Article  PubMed  Google Scholar 

Ubersax, J. A. & Ferrell, J. E. Jr. Mechanisms of specificity in protein phosphorylation. Nat. Rev. Mol. Cell Biol. 8, 530–541 (2007).

Article  PubMed  Google Scholar 

Needham, E. J., Parker, B. L., Burykin, T., James, D. E. & Humphrey, S. J. Illuminating the dark phosphoproteome. Sci. Signal 12, eaau8645 (2019).

Article  PubMed  Google Scholar 

Martin, E. W. & Holehouse, A. S. Intrinsically disordered protein regions and phase separation: sequence determinants of assembly or lack thereof. Emerg. Top. Life Sci. 4, 307–329 (2020).

Article  PubMed  Google Scholar 

Tobin, A. B. G-protein-coupled receptor phosphorylation: where, when and by whom. Br. J. Pharmacol. 153, S167–S176 (2008).

Article  PubMed  PubMed Central  Google Scholar 

Xu, C. & Min, J. Structure and function of WD40 domain proteins. Protein Cell 2, 202–214 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Chong, H., Lee, J. & Guan, K. L. Positive and negative regulation of Raf kinase activity and function by phosphorylation. EMBO J. 20, 3716–3727 (2001).

Article  PubMed  PubMed Central  Google Scholar 

Sundar, D. et al. Wild type p53 function in p53Y220C mutant harboring cells by treatment with Ashwagandha derived anticancer withanolides: bioinformatics and experimental evidence. J. Exp. Clin. Cancer Res. 38, 103 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Huang, Y. F. & Bulavin, D. V. Oncogene-mediated regulation of p53 ISGylation and functions. Oncotarget 5, 5808–5818 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Liu, N., Guo, Y., Ning, S. & Duan, M. Phosphorylation regulates the binding of intrinsically disordered proteins via a flexible conformation selection mechanism. Commun. Chem. 3, 123 (2020).

Article  PubMed