SH2 domains contain about 100 amino acid residues and exhibit a central antiparallel β-sheet centered between two α-helices.  Binding to phosphotyrosine-containing peptides involves  a strictly-conserved Arg residue that pairs with the negatively-charged phosphate on the phosphotyrosine, and a surrounding pocket that recognizes flanking sequences on the target peptide.  Compared to other signaling proteins, SH2 domains exhibit only a moderate degree of specificity for their target peptides, due to the relative weakness of the interactions with the flanking sequences. 
Over 100 human proteins are known to contain SH2 domains. A variety of tyrosine-containing sequences have been found to bind SH2 domains and are conserved across a wide range of organisms, performing similar functions.  Binding of a phosphotyrosine-containing protein to an SH2 domain may lead to either activation or inactivation of the SH2-containing protein, depending on the types of interactions formed between the SH2 domain and other domains of the enzyme.  Mutations that disrupt the structural stability of the SH2 domain, or that affect the binding of the phosphotyrosine peptide of the target, are involved in a range of diseases including X-linked agammaglobulinemia and severe combined immunodeficiency.