Abstract
Protein phosphorylation plays a crucial role in regulating a wide range of biological processes, and its dysregulation is strongly linked to various diseases. While many phosphorylation sites have been identified so far, their functionality and regulatory effects are largely unknown. Here, a deep learning model MMFuncPhos, based on a multi-modal deep learning framework, is developed to predict functional phosphorylation sites. MMFuncPhos outperforms existing functional phosphorylation site prediction approaches. EFuncType is further developed based on transfer learning to predict whether phosphorylation of a residue upregulates or downregulates enzyme activity for the first time. The functional phosphorylation sites predicted by MMFuncPhos and the regulatory types predicted by EFuncType align with experimental findings from several newly reported protein phosphorylation studies. The study contributes to the understanding of the functional regulatory mechanism of phosphorylation and provides valuable tools for precision medicine, enzyme engineering, and drug discovery. For user convenience, these two prediction models are integrated into a web server which can be accessed at http://pkumdl.cn:8000/mmfuncphos.