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  • The SH3 domain, often seen in signaling pathway proteins, frequently binds to a conserved PXXP Motif usually found in proline-rich regions of target proteins. The SH3 domain contains a site located between the RT and n-SRC loops that binds the PXXP motif, which then adopts a poly-proline type II (PPII) conformation. PXXP motifs are often clustered and have residues that contribute to binding specificity. Class I motifs have an amino to carboxy terminal binding orientation and include sites specific for the SRC oncoprotein. More promiscuous in their binding, Class II motifs have a carboxy to amino terminal binding orientation, PXXP can be in either of two positions, and they have basic residues at the C-terminus. (NCI)
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