Table 3. Mutually exclusive binding of domain pairs to the same protein segment.

		Protein and domain names
Name of the protein with the dual motifs	Position and sequence	Binding upon phosphorylation	Binding upon de-phosphorylation	References
CD3ε	162 PNPDYEPI 169	Zap70 (SH2)	Eps8L1 (SH3)	[88]
ARMS/Kidins220	1089 PPRPPSGYSQP 1099	CrkL (SH2)	CrkL (SH3)	[89]
Beta-Dystroglycan	887 PPPYVPP 893	c-Src (SH2)	Dystrophin (Class I WW)	[90]
Growth hormone receptor	534 YFCEADAKKCIPVAP 548	STAT5 (SH2)	Nck1 (SH3)	[91]–[93]
Cbl	540 RDLPPPPPPDRPYSVG 555	Fyn (SH2)	Src (SH3)	[94], [95]

Summary of literature-documented double switches. The second column includes protein sequences, where residues vital for SH2 binding and residues vital for SH3/class I WW binding are in bold and underlined, respectively. Rows (1–3) describe experimentally-verified double switches. Rows (4–5) include examples for which there is evidence for the motif binding to each domain, but not for a direct switch. Note that Y534 in growth hormone receptor is phosphorylated according to a high-throughput experiment. Also note that evidence for Fyn-Cbl interaction exists for the Cbl (552–614) fragment (spanning 62 residues), where Y552 is the only tyrosine, suggesting that this tyrosine is bound by the SH2 domain in Fyn.