. Author manuscript; available in PMC: 2016 Nov 1.

Published in final edited form as: Trends Pharmacol Sci. 2015 Oct 1;36(11):782–797. doi: 10.1016/j.tips.2015.07.004

Table 1.

Physiological substrates and implications of the mammalian N-end rule pathway

The mammalian N-end rule pathway	Substrates/Components	Physiological functions
Arg/N-end rule pathway	Cys2-RGS4	GPCR signaling pathway Cardiac development
	Cys2-RGS5
	Cys2-RGS16
	Leu2-RGS2	Hypertension Cardiovascular homeostasis
	Arg208-TDP43	Amyotrophic lateral sclerosis (ALS) Frontotemporal lobar degeneration (FTLD)
	Asp219-TDP43
	Asp247-TDP43
	Gln79-Synuclein	Parkinson’s disease (PD)
	Asp-Aβ42	Alzheimer’s disease (AD)
	Glu3-Tau	Alzheimer’s disease (AD)
	Glu19-Bip1	Protein quality control through autophagy
	PINK1	Mitochondria quality control through mitophagy
	Proapoptotic protein fragments	Apoptosis regulation
	myofibrils	Muscle wasting
	ATE1^−/−	Heart development
		Angiogenesis
		Hyperphagia
		Hyperkinesia
		Infertility
		Metabolic defects
	UBR1^−/−	Johanson-Blizzard Syndrome(JBS)
	UBR1^−/−UBR2^−/−	Neurogenesis
	UBR1^−/−UBR2^−/−	Cardiogenesis
	UBR4^−/−	Regulation of autophagic flux

Ac/N-end rule pathway	Met-Arg-RGS2	Hypertension Cardiovascular homeostasis
	Met-Gln-RGS2
	Met-Leu-RGS2