Editing SH3 domain (section)

==Peptide binding==
The classical SH3 domain is usually found in proteins that interact with other [[Protein|proteins]] and mediate assembly of specific protein complexes, typically via binding to [[proline]]-rich [[Peptide|peptides]] in their respective binding partner. Classical SH3 domains are restricted in humans to intracellular proteins, although the small human MIA family of extracellular proteins also contain a domain with an SH3-like fold.

Many SH3-binding epitopes of proteins have a [[consensus sequence]] that can be represented as a regular expression or [[Short linear motif]]:
 -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 [[hydrophobe|hydrophobic]] pocket of the SH3 domain. More recently, SH3 domains that bind to a core consensus motif R-x-x-K have been described. Examples are the C-terminal SH3 domains of adaptor proteins like Grb2 and Mona (a.k.a. Gads, Grap2, Grf40, GrpL etc.). Other SH3 binding motifs have emerged and are still emerging in the course of various molecular studies, highlighting the versatility of this domain.