Intrinsically disordered proteins play diverse roles in cell signaling

Table 1 Examples of regulatory mechanisms, enabled by intrinsic disorder, that contribute to cell signaling

Cell signaling requirement	ID-enabled mechanism	Example in this review
Signal diversification/specificity generation	Multi-protein binding	Reck-Fz-Wnt
	Varying IDRs via gene duplication	Wnt-Fz
	Varying IDRs via gene duplication	Connexins
	Post-translational modifications and/or alternative splicing	CXCR4
		GPCR-G protein
		VEGF versus VEGFB isoforms
Signal passage through a membrane	Binding-induced folding	EGFR
Integration of multiple inputs to diversify responses	Binding-induced folding	Glucocorticoid receptor EGFR
	Allostery	EGFR
	Post-translational modification	PTEN
Signal amplification	Phase separation	EGFR
	Scaffold-mediated concentration of components	Axin
	Scaffold-mediated concentration of components	Gab2
Signal propagation	Post-translational modification	EGFR
Signal propagation	Spatial control of protein binding/orientation	Ras EGFR
Graded or differential responses from the same protein	Spatial control of protein binding	NMDA receptor
Graded or differential responses from the same protein	Splicing and post-translational modifications	Glucocorticoid receptor

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