Motivation: Phosphorylation is involved in diverse signal transduction pathways. By predicting phosphorylation sites and their kinases from primary protein sequences, we can obtain much valuable information that can form the basis for further research. Using support vector machines, we attempted to predict phosphorylation sites and the type of kinase that acts at each site.
Results: Our prediction system was limited to phosphorylation sites catalyzed by four protein kinase families and four protein kinase groups. The accuracy of the predictions ranged from 83 to 95% at the kinase family level, and 76-91% at the kinase group level. The prediction system used-PredPhospho-can be applied to the functional study of proteins, and can help predict the changes in phosphorylation sites caused by amino acid variations at intra- and interspecies levels.
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http://dx.doi.org/10.1093/bioinformatics/bth382 | DOI Listing |
FEBS J
January 2025
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Microtubule associated protein 2 (MAP2) interacts with the regulatory protein 14-3-3ζ in a cAMP-dependent protein kinase (PKA) phosphorylation dependent manner. Using selective phosphorylation, calorimetry, nuclear magnetic resonance, chemical crosslinking, and X-ray crystallography, we characterized interactions of 14-3-3ζ with various binding regions of MAP2c. Although PKA phosphorylation increases the affinity of MAP2c for 14-3-3ζ in the proline rich region and C-terminal domain, unphosphorylated MAP2c also binds the dimeric 14-3-3ζ via its microtubule binding domain and variable central domain.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Department of Chemistry, Faculty of Science, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
Tau is a microtubule (MT)-associated protein that binds to and stabilizes the MTs of neurons. Due to its intrinsically disordered nature, it undergoes several post-translational modifications (PTMs) that are intricately linked to both the physiological and pathophysiological roles of Tau. Prior research has shown phosphorylation and O-GlcNAcylation to have contrasting effects on Tau aggregation; however, the precise molecular mechanisms and potential synergistic effects of these modifications remain elusive.
View Article and Find Full Text PDFNat Commun
January 2025
Mechanisms, Biomarkers and Models Section - Genome Stability Group, Department of Environment and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299 - 00161, Rome, Italy.
The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.
View Article and Find Full Text PDFInt J Surg
January 2025
Department of Anesthesiology, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, Nanchang, Jiangxi Province, China.
Nerve growth factor (NGF) is critical in regulating the homeostasis of microglial cells. It activates various signaling pathways that mediate the phosphorylation of cAMP response element-binding protein (CREB) at key regulatory sites. The decrease in phosphorylated CREB (p-CREB) expression is linked to neuroinflammatory responses.
View Article and Find Full Text PDFReplication protein A (RPA) is a heterotrimeric single-strand DNA binding protein that is integral to DNA metabolism. Segregation of RPA functions in response to DNA damage is fine-tuned by hyperphosphorylation of the RPA32 subunit that is dependent on Cyclin-dependent kinase (Cdk)-mediated priming phosphorylation at the Ser-23 and Ser-29 sites. However, the mechanism of priming-driven hyperphosphorylation of RPA remains unresolved.
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