Table 2.

Interacting proteins related to Small GTPases (Ras family).

Small GTPase	Interacting proteins	Related diseases/function	Pathway/mechanism	References
Rit2 (Rin)	NGF	Alzheimer’s disease	Increased RAS/MAPK	Besga et al., 2017
		Huntington’s disease	Increased AKT/mTOR	Chaldakov et al., 2009; Zhang et al., 2013
	RIT1	Noonan syndrome	Increased RAS/MAPK, Rac, and Stat3	Yaoita et al., 2016
		Mental retardation, microcephaly, and epilepsy		Sonmez et al., 2017
	TECR	Non-syndromic mental retardation	Increased RAS/MAPK	Caliskan et al., 2011
	NTRK1	Hereditary sensory and autonomic neuropathy type V	A mutation in the NTRK1/high-affinity nerve growth factor (TrkA) gene	Houlden et al., 2001
		Congenital insensitivity to pain with anhidrosis
	POU4F1	Autism	Copy number variations (CNVs)	Indo, 2001
Rit1 (Rit)	B-Raf	Neuronal development and regeneration	Activation of the B-Raf/ERK and p38 MAP kinase cascades	Salyakina et al., 2011
	p38 MAPK	Neurite outgrowth and cell survival
	MK2	Cell survival	Rit GTPase-p38-MK2-AKT 9 kinase survival pathway	Shi and Andres, 2005
	HSP27	Cell survival	MK2 signaling complex	Shi et al., 2013
	Akt	Cell survival	p38–MK2–HSP27-Akt activation	Shi et al., 2011
	RGL3	RalA activation	A candidate effector for Rit and Ras	Shao and Andres, 2000
Rheb	mTOR	Promoting growth, cell cycle progression and inhibition of autophagy	Growth factor-induced mTORC1 activation	Sokolov et al., 2018
	TSC complex	Form a complex with Rheb at the lysosomal membranes	Growth factor-induced mTORC1 activation	Lim and Crino, 2013
	PLD1	Rheb binds and activates phospholipase D1 (PLD1) in a GTP-dependent manner	mTORC1 activation	Zheng et al., 2014
	GAPDH	GAPDH regulates mTOR activity by sequestering the Rheb.	Rheb–GAPDH interaction	Lee et al., 2009
	FKBP38	Coordinate membrane targeting of Rheb	Rheb interacts with FKBP38 and prevents its association with mTOR	De Cicco et al., 2018
	RASSF1	Rheb form complex with RASSF1A to coordinate Hippo and TOR signaling	Hippo pathway activator	Nelson and Clark, 2016
	NIX LC3	Rheb interacts with mitochondrial autophagic receptor Nix and the autophagosomal protein LC3-II.	Activation of mitophagy	Melser et al., 2013 Sugiura et al., 2015
	Syntenin	PDZ protein syntenin preferentially binds to the GDP-bound form of Rheb.	Rheb-syntenin signaling	Sato et al., 2015
	CAD	Rheb binds to CAD protein, a multifunctional enzyme required for the synthesis of pyrimidine nucleotides.	CAD binding is more pronounced with Rheb2 than with Rheb1	Tyagi et al., 2015
	PERK	Rheb inhibits protein synthesis by activating the PERK-eIF2α signaling	Phosphorylation of eIF2α and PERK interplay	Shahani et al., 2017
	BACE1	Aging and Alzheimer’s disease. Forebrain Rheb promotes aging-associated cognitive defects	Rheb depletion increased the levels of BACE1