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.

Structure Reference

  1. Waksman, G. et al. (1993) Cell 72(5): 779–90.

Examples of Domain Proteins

Phospho/Tyr Binding: SH2 Domain

Binding Examples

SH2 Domain Proteins Binding Partners Phosphopeptide Ligand SH2 Specificity Residues
    Regulation Specificity  
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