Phospho/Tyr Binding: SH2 Domain
Src SH2 domain bound to phosphotyrosine peptide (red).
Domain Binding and Function
Src-homology 2 (SH2) domains are modules of approximately 100 amino acids that bind to specific phospho (pY)-containing peptide motifs. Conventional SH2 domains have a conserved pocket that recognizes pY, and a more variable pocket that binds 3-6 residues C-terminal to the pY to confer specificity. The SAP SH2 domain recognizes Y as well as pY in the context of residues N and C terminal, suggesting that an alternate 3-pronged model may sometimes apply. Phosphopeptides of optimal sequence bind to SH2 domains with dissociation constants of ~50-500 nM.
- Waksman, G. et al. (1993) Cell 72(5): 779–90.
Examples of Domain Proteins
|SH2 Domain Proteins||Binding Partners||Phosphopeptide Ligand||SH2 Specificity Residues|
|Src Tyrosine Kinase||Focal Adhesion Kinase||pTyr||-Ala-Glu-Ile||Tyr ΒD5|
|Phospho-lipase C-γ C-terminal SH2||PDGF β receptor||pTyr||-Ile-Ile-Pro-Leu-Pro-Asp||Cys ΒD5|
|Grb2 adaptor||Shc docking protein||pTyr||-Val-Asn-Val||Trp EF1|