Phosphosite

A phosphosite is a specific residue within a protein at which a phosphate group can be covalently attached through the process of phosphorylation. Common phosphosites occur on the hydroxyl-containing amino acids serine, threonine, and tyrosine, although other residues can be modified less frequently. Phosphorylation is catalyzed by protein kinases and reversed by phosphatases, forming a reversible post-translational modification that modulates protein function.

Phosphosites influence many aspects of protein behavior, including enzymatic activity, subcellular localization, stability, and interactions with other macromolecules. They often reside in intrinsically disordered regions or loop segments and are frequently found within short sequence motifs recognized by specific kinases. The presence, absence, and stoichiometry of phosphorylation at a given site can change dynamically in response to cellular signals, developmental cues, or environmental stresses.

Identification and characterization of phosphosites rely primarily on techniques such as mass spectrometry-based phosphoproteomics and phospho-specific antibodies, supplemented by mutagenesis, kinase assays, and bioinformatic prediction. Experimental mapping of sites and their regulatory kinases is central to understanding signaling networks.

Phosphosites have biomedical relevance because aberrant phosphorylation patterns are associated with diseases including cancer, neurodegeneration, and metabolic disorders. Catalogs and databases that compile experimentally validated phosphosites serve as resources for research and drug discovery, facilitating the study of signaling pathways and potential therapeutic targets.