SH2domein

SH2domein, also known as the Src Homology 2 (SH2) domain, is a conserved protein domain of about 100 amino acids that mediates protein–protein interactions in intracellular signaling. Named for its initial identification in Src-family kinases, the SH2 domain is now found in a wide range of signaling proteins, including adaptor proteins and protein tyrosine kinases. Its primary function is to bind phosphotyrosine-containing motifs, allowing recruited signaling components to associate with activated receptors and phosphorylated substrates.

Structure and binding: The SH2 domain folds into a characteristic compact core and forms a phosphotyrosine-binding pocket, created in part by a conserved arginine that coordinates the phosphate group. Binding is dependent on the presence of a phosphotyrosine and is influenced by specific residues flanking the phosphotyrosine, producing preferences for particular pY+1 to pY+3 motifs across different SH2 domains.

Function and significance: By bridging phosphotyrosine signals to downstream effectors, SH2 domains coordinate numerous signaling pathways, including receptor tyrosine kinase, cytokine, and immune receptor signaling. They contribute to the assembly of signaling complexes, for example Grb2-SH2 linking activated receptors to Ras signaling. Mutations or dysregulation of SH2-containing proteins are associated with diseases such as cancer and immune disorders. SH2 domains are common targets in research and drug development, with approaches aimed at inhibiting specific SH2–phosphotyrosine interactions.