Table 1.

The substrates of SIRT6.

Enzymatic action	Substrates		Site	Physiological function
Deacetylation	Histones	H3K9	K9	Modulate telomeric chromatin,14 NF-κB-dependent gene expression.17 Control glycolytic genes expression.42 Regulate cancer cell apoptosis.79
		H3K56	K56	DSB repair and genomic stability.7
		H3K18	K18	Pericentric transcriptional silencing.45
	Nonhistones	GCN5	K549	Regulate the transcription of gluconeogenic gene PGC-1α.46
		PKM2	K433	Suppress PKM2 nuclear localization and oncogenic functions.47
		Ku70	K542	Attenuate Bax-mediated apoptosis in HCC.48
		NAMPT	K53/369	Regulate the enzymatic activity of NAMPT and the secretion of eNAMPT, respectively.49
		XBP1s	K257/297	Promote XBP1s protein degradation and confers resistance to hepatic steatosis.50
		SOD2	K68/122	Regulation of antidepressant response.51
		Prdx6	K63/209	Regulation of antidepressant response.51
		SMAD3	K333/378	Protect against liver fibrosis.53
		SMAD2	K54	Protect against liver fibrosis.52
		P53	K382	Regulation of apoptosis and stress resistance.54,55
Mono-ADP-ribosylation	Nonhistones	SIRT6		Mono-ADP-ribosylation SIRT6.58
		PARP1	K521	Prompt the DSB repair.5
		KAP1		Repress LINE1 retrotransposons.20
		BAF170	K312	Protect cells from oxidative stress.60
		KDM2A		Promote DNA repair.61
Defatty-acylation	Histones	H3K9, H3K18, H3K2732,64	K9/18/27
	Nonhistones	TNF-α	K19/20	Regulate the secretion of TNF-α.32
		R-Ras2		Suppress the plasma membrane localization of R-Ras2.63