EPQpYEEIPIYL, a phosphopeptide, is a Src homology 2 (SH2) domain ligand. EPQpYEEIPIYL activates Src family members (e.g. Lck, Hck, Fyn) by binding to SH2 domains[1][2].
The hmT-derived phosphopeptide, pY324, which has the sequence EPQpYEEIPIYL, shows the highest affinity binding to GST fusion proteins of the Lck SH2 domain (5-fold higher than Lck’s affinity-for the Lck tail phosphopeptide) and the Src SH2 domain (44-fold higher than Src’s affinity for the Src tail phosphopeptide)[1].
[1]. G Payne, et al. The phosphopeptide-binding specificity of Src family SH2 domains. Chem Biol. 1994 Oct;1(2):99-105.
[2]. T D Mulhern, et al. The SH2 domain from the tyrosine kinase Fyn in complex with a phosphotyrosyl peptide reveals insights into domain stability and binding specificity. Structure. 1997 Oct 15;5(10):1313-23.