SH3 domain

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Ribbon diagram of the SH3 domain, α-spectrin, from chicken (Gallus gallus) (PDB accession code 1SHG), colored from blue (N-terminus) to red (C-terminus).

The Src homology 3 domain (or SH3 domain) is a small protein domain of about 60 amino acid residues first identified as a conserved sequence in the non-catalytic part of several cytoplasmic tyrosine kinases such as Abl and Src and it has been then identified in several other protein families such as: phospholipases, PI3 Kinase, ras GTPase activating protein, adaptor proteins, CDC24 and CDC25. The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β sheets. The linker regions may contain short helices. The SH3 domain is found in proteins that interact with other proteins and they mediate assembly of specific protein complexes via binding to proline-rich peptides in their respective binding partner.

SH3-binding domains have a consensus sequence:

-X-P-p-X-P-
 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.