-
SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine
Jiang, H.; Khan, S.; Wang, Y.; Charron, G.; He, B.; Sebastian, C.; Du, J.; Kim, R.; Ge, E.; Mostoslavsky, R.; Hang, H.C.; Hao, Q.; Lin, H.; Nature 496, 110-113 (2013) 
Data extracted from this reference:
Cloned(Commentary)
Commentary
Organism
Homo sapiens
Crystallization (Commentary)
Crystallization
Organism
hanging drop vapor diffusion method at 18°C, crystal structure of Sirt6 in complex with a histone H3 K9 myristoyl peptide and ADPribose at 2.2 A resolution
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
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
Homo sapiens
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0009
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0024
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
0.0034
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0045
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
0.04
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.2
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.81
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
Homo sapiens
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
Q8N6T7
-
-
Purification (Commentary)
Commentary
Organism
-
Homo sapiens
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
Sirt6 prefers long chain fatty acyl groups. Low deacetylase activity on histone H3 K9 and histone H3 K56. Selectivity for peptide sequence is not high
730464
Homo sapiens
?
-
-
-
-
NAD+ + [histone H3 peptide]-N6-acetyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-butyryl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-butyryl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-myristoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-octanoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-octanoyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-palmitoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-palmitoyl-ADP-ribose
-
-
-
?
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
-
730464
Homo sapiens
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine19 + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
-
730464
Homo sapiens
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine20 + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
730464
Homo sapiens
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-myristoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [tumor necrosis factor alpha]-L-lysine + 2'-O-myristoyl-ADP-ribose
-
-
-
?
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.002
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
0.0021
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0027
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0039
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0046
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0049
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.005
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
assay at
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
-
Homo sapiens
Crystallization (Commentary) (protein specific)
Crystallization
Organism
hanging drop vapor diffusion method at 18°C, crystal structure of Sirt6 in complex with a histone H3 K9 myristoyl peptide and ADPribose at 2.2 A resolution
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
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
Homo sapiens
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0009
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0024
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
0.0034
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0045
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
0.04
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.2
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.81
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
Homo sapiens
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
-
-
?
Purification (Commentary) (protein specific)
Commentary
Organism
-
Homo sapiens
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
Sirt6 prefers long chain fatty acyl groups. Low deacetylase activity on histone H3 K9 and histone H3 K56. Selectivity for peptide sequence is not high
730464
Homo sapiens
?
-
-
-
-
NAD+ + [histone H3 peptide]-N6-acetyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-butyryl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-butyryl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-myristoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-octanoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-octanoyl-ADP-ribose
-
-
-
?
NAD+ + [histone H3 peptide]-N6-palmitoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-palmitoyl-ADP-ribose
-
-
-
?
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
-
730464
Homo sapiens
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine19 + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
-
730464
Homo sapiens
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine20 + 2'-O-myristoyl-ADP-ribose
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
730464
Homo sapiens
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-myristoyl-L-lysine
-
730464
Homo sapiens
nicotinamide + [tumor necrosis factor alpha]-L-lysine + 2'-O-myristoyl-ADP-ribose
-
-
-
?
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.002
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
0.0021
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0027
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0039
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0046
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.0049
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.005
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
8
-
assay at
Homo sapiens
General Information
General Information
Commentary
Organism
metabolism
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
Homo sapiens
General Information (protein specific)
General Information
Commentary
Organism
metabolism
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
Homo sapiens
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.0048
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.01
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.12
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.14
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.83
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
1.1
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
3
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
0.0048
-
[histone H3 peptide]-N6-acetyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.01
-
[histone H3 peptide]-N6-butyryl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.12
-
[histone H3 peptide]-N6-octanoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.14
-
[histone H3 peptide]-N6-myristoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
0.83
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
pH 8.0, 37°C
Homo sapiens
1.1
-
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
pH 8.0, 37°C
Homo sapiens
3
-
[histone H3 peptide]-N6-palmitoyl-L-lysine
pH 8.0, 37°C
Homo sapiens
Other publictions for EC 2.3.1.B41
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
737930
Cea
Evidence for a role of the his ...
Homo sapiens
Blood
127
1138-1150
2016
-
-
-
-
-
-
-
-
-
-
1
1
-
2
-
-
-
-
-
1
-
-
1
1
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
1
1
-
-
-
-
-
1
-
-
1
1
-
-
-
-
-
-
-
-
-
2
2
-
-
-
738060
Rahnasto-Rilla
N-acylethanolamines bind to SI ...
Homo sapiens
ChemBioChem
17
77-81
2016
12
-
1
-
-
-
3
1
-
-
-
2
-
1
-
-
1
-
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
2
12
-
1
1
-
-
-
2
3
-
1
-
-
-
2
-
-
-
1
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
739139
Zhang
Identifying the functional con ...
Homo sapiens
Nat. Chem. Biol.
12
614-620
2016
-
-
1
-
4
-
-
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
4
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
1
-
4
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
739158
Tasselli
SIRT6 deacetylates H3K18Ac at ...
Homo sapiens
Nat. Struct. Mol. Biol.
23
434-440
2016
-
-
-
-
1
-
-
-
-
-
-
1
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
739225
Liu
Cyclic peptide-based potent hu ...
Homo sapiens
Org. Biomol. Chem.
14
5928-5935
2016
-
-
-
-
-
-
2
-
-
-
-
1
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
730473
Cardinale
Biochemical characterization o ...
Mus musculus
Neurochem. Res.
40
59-69
2015
-
-
1
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
1
1
1
1
-
-
737946
Hwang
SIRT6 protein deacetylase inte ...
Mus musculus
BMC Mol. Biol.
16
12
2015
-
-
1
-
1
-
-
-
-
-
-
1
-
3
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
1
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
737977
Feng
Sirtuin 6 promotes transformin ...
Homo sapiens
Cancer Sci.
106
559-566
2015
-
-
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
3
-
-
1
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
3
-
-
1
-
-
-
-
-
-
-
-
-
1
1
1
1
-
-
738169
Zhang
The histone deacetylase SIRT6 ...
Homo sapiens
Eur. Rev. Med. Pharmacol. Sci.
19
818-824
2015
-
1
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
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Mechanism of sirtuin inhibitio ...
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