Understanding protein functions is critical for metagenomic research, disease mechanism elucidation, and rational drug discovery. Traditional biochemical methods to determine protein functions are often inefficient and costly, leading to a widening gap between the rapid accumulation of protein sequences and their functional annotations. To address this, we introduce GPSFun, a fast and accurate web server that provides comprehensive geometry-aware protein sequence function annotations, including protein-binding sites for multiple ligands, gene ontologies, subcellular locations, and protein solubility. GPSFun’s web server can be accessed at https://bio-web1.nscc-gz.cn/app/GPSFun , offering users a result with a rich visualized interface. Additionally, GPSFun was adopted to annotate ligand-binding sites for over 568,000 proteins from Swiss-Prot, leading to a complementary database named GPSiteDB ( https://bio-web1.nscc-gz.cn/database/GPSiteDB ). In this chapter, we first overview the workflow and results of our method, and then, we provide a step-by-step instruction on the usage of GPSFun and GPSiteDB, along with the detailed interpretations of the corresponding results.