SH2 domains are not present in yeast and appear at the boundary between protozoa and animalia in organisms such as the social amoeba Dictyostelium discoideum.
A detailed bioinformatic examination of SH2 domains of human and mouse reveals 120 SH2 domains contained within 115 proteins encoded by the human genome, representing a rapid rate of evolutionary expansion among the SH2 domains.
A large number of SH2 domain structures have been solved and many SH2 proteins have been knocked out in mice.