Table 1.

Summary of Biochemical Properties of the RAS Proteins Grouped into Five Classes

Classes	RAS mutant	mant-GppNHp association	Intrinsic mantGDP dissociation	GEF-catalyzed mantGDP dissociation	Intrinsic GTPase	GAP-stimulated GTPase	RAF-RBD binding
Controls	wt	1.3a	0.00003a	0.09a	0.0093a	9.3a	0.22b
	G12V	≈	≈	≈	↓
	F28L		↑	↑	≈	↓
A	K5N	⇩	≈	≈	≈	≈	≈
	T58I	≈	↑	≈	≈	≈
	E153V	↓	≈	≈	≈	≈
B	V14I	↓	⇧	⇧	≈	≈
C	Q22R	↓	≈	≈	≈	⇩	≈
D	Q22E	↓	⇧	⇧	≈	⇩
	F156L	↓		⇧	≈	⇩
E	P34L	≈	≈	≈	≈
	P34R	≈	≈	≈	≈
	G60R	↓	≈		↓

Based on our biochemical data, RAS mutants are grouped into different functional classes: (A) no major changes; (B) increase in intrinsic and catalyzed nucleotide exchange; (C) decrease in GAP-stimulated GTPase; (D) increase in intrinsic and catalyzed nucleotide exchange and decreased in GAP-stimulated GTPase; (E) defective interaction with GAPs and effectors and also with GEFs in the case of RAS^G60R. RAS^wt, RAS^G12V, and RAS^F28L were included as controls. Black arrows outlines effects that favor increased signaling, gray arrows those impaired signaling, such as lower affinity of effectors. ≈≥ 2-fold, ↓or ↑ = 3–15-fold, ⇩or ⇧ = 15–40-fold, or > 40-fold relative to RAS^wt values. Relative values are shown in Table S4.

^aObserved rate constants (k_obs) in sec⁻¹.

^bDissociations constants (K_d) in µM.