The Src homology 3 (SH3) region is a small protein domain of approximately 60 amino acids present in a large group of proteins. In general, it exists in association with catalytic domains, as in the nonreceptor protein-tyrosine kinases and phospholipase C-? within structural proteins, such as spectrin or Myosin; and in small adapter proteins, such as Crk and GRB2. SH3 domains are often accompanied by SH2 domains of 100 amino acids, which bind to tyrosine-phosphorylated regions of target proteins, frequently linking activated growth factors to putative signal transduction proteins. The functions of SH3 domains are not as well defined. Deletion or mutation of SH3 domains generally activate the transforming potential of nonreceptor tyrosine kinases, suggesting that SH3 mediates negative regulation of an intrinsic transforming activity. 3BP1 has been identified as a protein with a high affinity proline-rich binding site for the SH3 domain of c-Abl p120. A similar putative adapter protein, designated Slap, for Src-like adapter protein, has been cloned. Slap contains a single SH2 and SH3 domain that exhibits homology with those from members of the Src kinase family. The N- and C-termini, however, are unique.