2.3.1.B41	D63H	naturally occuring mutation in SIRT6, the homozygous inactivating mutation of histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses, it causes human perinatal lethality, missense mutation SIRT6 p.D63H in affected fetal amniocytes. SIRT6 D63H mutant mESCs fail to form EBs and retain pluripotent gene expression. The amino acid change at Asp63 to a histidine results in virtually complete loss of H3K9 deacetylase and demyristoylase functions. Asp63 is located in the NAD+-binding pocket, forming hydrogen bonds with neighboring amino acids and thus providing structure to the NAD+-binding loop	756879	
2.3.1.B41	D63H	naturally occuring mutation in SIRT6, the homozygous inactivating mutation of histone deacetylase SIRT6. Asp63 is located in the NAD+-binding pocket, forming hydrogen bonds with neighboring amino acids and thus providing structure to the NAD+-binding loop	756879	
2.3.1.B41	G60A	inactive	737946	
2.3.1.B41	G60A	the mutant is a lysine defatty acylase in vitro with substantially decreased deacetylase activity in vitro and no detectable deacetylase activity in cells	739139	
2.3.1.B41	G60A	the SIRT6 G60A mutant retains an efficient defatty-acylase activity, but has significantly decreased deacetylase activity	757667	
2.3.1.B41	H131Y	the mutant enzyme can still bind NAD+ but has a decreased ability to bind ADP-ribose	729972	
2.3.1.B41	H133Y	a catalytically inactive mutant of SIRT6, the acetylation level of PER2 is significantly increased in SIRT6-KO HEK293 cells compared to wild-type	755978	
2.3.1.B41	H133Y	catalytically inactive SIRT6 mutant, the SIRT6 H133Y mutant without histone deacetylase activity fails to inhibit phosphorylation and nuclear translocation of Smad2	757294	
2.3.1.B41	H133Y	inactive	739139, 739158	
2.3.1.B41	H133Y	inactive enzyme mutant	756407	
2.3.1.B41	H133Y	when human Sirt6 wild-type enzyme is overexpressed in Sirt6 KO MEF cells, tumor necrosis factor alpha has lower fatty acylation level than tumor necrosis factor alpha from cells without overexpression of human Sirt6, while overexpression of human Sirt6 H133Y catalytic mutant does not have much effect on tumor necrosis factor alpha fatty acylation	730464	
2.3.1.B41	K160A	site-directed mutagenesis, the mutant's activability is similar compared to the wild-type enzyme	757236	
2.3.1.B41	K81A	site-directed mutagenesis, the activability of the mutant is only slightly reduced compared to the wild-type enzyme	757236	
2.3.1.B41	M70R	further decrease in nicotinamide sensitivity compared to wild-type	730706	
2.3.1.B41	additional information	construction of the interfering adenovirus vector, specific short hairpin RNA (shRNA) for the bovine SIRT6 gene are designed, usage of shRNA-399 for SIRT6 gene silencing	755904	
2.3.1.B41	additional information	enzyme knockout by SIRT6 siRNA expression. SIRT6 overexpression in hepatocellular carcinoma cells reduces E-cadherin levels	757530	
2.3.1.B41	additional information	generation of brS6KO mice, phenotype, overview. Brains of brS6KO mice are significantly smaller, but otherwise structurally normal. brS6KO mice exhibit increased signs of DNA damage, marked by increased levels of ATM and H2AX phosphorylation, increased H3K56ac, and reduced SNF2H recruitment to chromatin. A significant increase in apoptotic cells in the cortex is observed, as determined by TUNEL staining in young mice (3-4 month old). SIRT6-deficient brains have increased signs of DNA damage and cell death. Behavioral defects of brS6KO mice, overview. SIRT6 deletion markedly decreases non-associative (OF) and associative (CFC) learning. SIRT6KO cells are more sensitive to apoptosis, prevented by GSK3 or ATM inhibition	756392	
2.3.1.B41	additional information	generation of endothelium-specific SIRT6 knockout mice (Tie2-Cre/SIRT6flox/flox, defined as ecSIRT6-/-). Analysis of the effect of endothelium-specific SIRT6 depletion on hyperlipidemic mice	756672	
2.3.1.B41	additional information	generation of muscle-specific knockout mice SIRT6M -/- and effects of different diets, phenotypes, detailed overview	-, 755766	
2.3.1.B41	additional information	generation of SIRT6 knockout human mesenchymal stem cells (hMSCs) by targeted gene editing. For generation of SIRT6-deficient human embryonic stem cells (hESCs), the exon 1 of SIRT6 gene is removed in hESCs by a transcription activator-like effector nuclease. SIRT6-deficient hMSCs exhibit accelerated functional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs are predominately characterized by dysregulated redox metabolism and increased sensitivity to the oxidative stress. SIRT6 forms a protein complex with both nuclear factor erythroid 2-related factor 2 (NRF2) and RNA polymerase II, which is required for the transactivation of NRF2-regulated antioxidant genes, including heme oxygenase 1 (HO-1). Phenotype, overview	756407	
2.3.1.B41	additional information	generation of SIRT6 knockout MEF cells which exhibit an increased basal level of mobility compared to that in wild-type cells before damage. But the cells do not show the damage-induced increase in total movement after damage	758437	
2.3.1.B41	additional information	generation of SIRT6-overexpressing human umbilical vein endothelial cells (HUVECS), significantly fewer THP-1 cells adher to SIRT6-overexpressing HUVECs exposed to minute CCs compared to control HUVECs	756672	
2.3.1.B41	additional information	generation of SIRT6KO cells from SH-SY5Y cells	756392	
2.3.1.B41	additional information	knockdown of SIRT6 in HepG2 cells	756689	
2.3.1.B41	additional information	lentiviral short hairpin RNA-mediated knockdown of SIRT6 in A-375 and Hs 294T human melanoma cells significantly decreased cell growth, viability, and colony formation, induced G1-phase arrest and increased senescence-associated beta-galactosidase staining. SIRT6 knockdown in A375 cells causes significant modulation in several genes and/or proteins, i.e. it decreases in AKT1, ATG12, ATG3, ATG7, BAK1, BCL2L1, CLN3, CTSB, CTSS, DRAM2, HSP90AA1, IRGM, NPC1, SQSTM1, TNF, and BECN1 expression and increases in GAA, ATG10 expression	756871	
2.3.1.B41	additional information	overexpression of SIRT6 in HFL1 cells infected with an adenoviral vector encoding SIRT6 or knockdown by an adenoviral vector encoding SIRT6 short hairpin RNA	757294	
2.3.1.B41	additional information	SIRT6 overexpression abrogates the toxicity of primary astrocytes expressing ALS-linked mutant SOD1 G93A. SIRT6 plays a central role in the protection conferred by enhancing NAD+ availability in hSOD1G93A astrocytes	756691	
2.3.1.B41	additional information	specific downregulation of histone deacetylase sirtuin 6 (SIRT6), overexpression of SIRT6. In Hep-G2 cells, doxorubicin treatment results in significant increases in SIRT1 and SIRT4 mRNA expression and downregulation of SIRT6 mRNA level by 36 h	757883	
2.3.1.B41	R65A	site-directed mutagenesis, the SIRT6 variant cannot be stimulated toward deacetylation by activator compounds. The R65A variant is similarly deficient in the ability to display enhanced catalysis with myristoylated substrates, suggesting that common catalytic steps are hampered	757236	
2.3.1.B41	R65A	the mutant shows only ADP-ribosyltransferase activity but no deacetylase activity	739139	
2.3.1.B41	R76A	site-directed mutagenesis, the activability of the mutant is only slightly reduced compared to the wild-type enzyme	757236	
2.3.1.B41	S56Y	inactive	739139	
2.3.1.B41	Y12F	the mutant exhibits deacetylase activity similar to that of the wild type enzyme	738283	
2.3.1.B41	Y148F	the mutant shows 57% decrease of activity compared to the wild type enzyme	738283	
2.3.1.B41	Y257F	the mutant shows 73% decrease of activity compared to the wild type enzyme	738283	
2.3.1.B41	Y5F	the mutant exhibits deacetylase activity similar to that of the wild type enzyme	738283