An SH3 domain is a protein module, a characteristic peptide sequence. It is used in signal transduction proteins, often in pathways involving tyrosin kinases. SH3 domains bind to proline-rich sequences (or polyproline helices). SH stands for src homology.

SH3 domains have a consensus sequence:

 1 2 3 4 5
with 1 and 4 being aliphatic amino acids, 2 and 5 always and 3 sometimes being proline. The sequence binds to the hydrophobic pocket of the SH3 domain.

SH3 domains are often found in functions concerning the cytoskeleton, the ras protein, and the src kinase. They also increase the substrate specificity of tyrosine kinases by binding far away from the catalytic center of the kinase.