Information on EC 2.4.2.B16 - protein-long-chain fatty-acyl-lysine deacylase (NAD+)

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The expected taxonomic range for this enzyme is: Archaea, Eukaryota

EC NUMBER
COMMENTARY hide
2.4.2.B16
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
protein-long-chain fatty-acyl-lysine deacylase (NAD+)
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
NAD+ + [protein]-N6-palmitoyl-L-lysine = nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
show the reaction diagram
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD+ + Ac-AK(N6-acetyl)K-7-amido-4-methylcoumarin
nicotinamide + Ac-AKK-7-amido-4-methylcoumarin + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the substrate is based on the human tumour suppressor protein p53
-
-
?
NAD+ + Ac-HK(N6-acetyl)K-7-amido-4-methylcoumarin
nicotinamide + Ac-HKK-7-amido-4-methylcoumarin + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the substrate is based on the human tumour suppressor protein p53
-
-
?
NAD+ + Ac-RHK(N6-acetyl)K-7-amido-4-methylcoumarin
nicotinamide + Ac-RHKK-7-amido-4-methylcoumarin + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the substrate is based on the amino acids 379-382 of the human tumour suppressor protein p53
-
-
?
NAD+ + Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
nicotinamide + Ac-RYQK-7-amido-4-methylcoumarin + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the peptide substrate mimics the biological deacetylation site of histone H3 K56
-
-
?
NAD+ + Ac-TAR(N6-acetyl)K-7-amido-4-methylcoumarin
nicotinamide + Ac-TARK-7-amido-4-methylcoumarin + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the peptide substrate mimics the biological deacetylation site of histone H3 K9
-
-
?
NAD+ + KGLGKGGA(N6-acetyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the enzyme shows increased reaction velocity with increasing acyl chain length. As compared to its deacetylating activity, Sir2Af2 depropionylates, debutyrylates, and demyristoylates a peptide of the same sequence at 1.5-, 1.9-, and 3.4-fold higher rates, respectively
-
-
?
NAD+ + KGLGKGGA(N6-butyryl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
show the reaction diagram
-
the enzyme shows increased reaction velocity with increasing acyl chain length. As compared to its deacetylating activity, Sir2Af2 depropionylates, debutyrylates, and demyristoylates a peptide of the same sequence at 1.5-, 1.9-, and 3.4-fold higher rates, respectively
-
-
?
NAD+ + KGLGKGGA(N6-myristoyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
-
the enzyme shows increased reaction velocity with increasing acyl chain length. As compared to its deacetylating activity, Sir2Af2 depropionylates, debutyrylates, and demyristoylates a peptide of the same sequence at 1.5-, 1.9-, and 3.4-fold higher rates, respectively
-
-
?
NAD+ + KGLGKGGA(N6-propionyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
show the reaction diagram
-
the enzyme shows increased reaction velocity with increasing acyl chain length. As compared to its deacetylating activity, Sir2Af2 depropionylates, debutyrylates, and demyristoylates a peptide of the same sequence at 1.5-, 1.9-, and 3.4-fold higher rates, respectively
-
-
?
NAD+ + QTAR(N6-decanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + QTAR(N6-dodecanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-dodecanoyl-ADP-ribose
show the reaction diagram
-
dodecanoylated histone H3 peptide, about 60% compared to the activity with the decanoylated peptide
-
-
?
NAD+ + QTAR(N6-hexanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-propionyl-ADP-ribose
show the reaction diagram
-
hexanoylated histone H3 peptide, about 20% compared to the activity with the decanoylated peptide
-
-
?
NAD+ + QTAR(N6-myristoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
show the reaction diagram
-
myristoylated histone H3 peptide, about 60% compared to the activity with the decanoylated peptide
-
-
?
NAD+ + QTAR(N6-octanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-octanoyl-ADP-ribose
show the reaction diagram
-
octanoylated histone H3 peptide, about 50% compared to the activity with the decanoylated peptide
-
-
?
NAD+ + SKEYFS(N6-acetyl)KQK
nicotinamide + SKEYFSKQK + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [histone H3 peptide]-N6-acetyl-L-lysine
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H3 peptide]-N6-butyryl-L-lysine
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-butyryl-ADP-ribose
show the reaction diagram
NAD+ + [histone H3 peptide]-N6-myristoyl-L-lysine
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H3 peptide]-N6-octanoyl-L-lysine
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-octanoyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H3 peptide]-N6-palmitoyl-L-lysine
nicotinamide + [histone H3 peptide]-L-lysine + 2'-O-palmitoyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [histone H3]-N6-acetyl-L-lysine
nicotinamide + [histone H3]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H4]-N6-acetyl-L-lysine
nicotinamide + [histone H4]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine19 + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
nicotinamide + [synthetic tumor necrosis factor alpha peptide]-L-lysine20 + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
show the reaction diagram
-
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-myristoyl-L-lysine
nicotinamide + [tumor necrosis factor alpha]-L-lysine + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NAD+ + [histone H3]-N6-acetyl-L-lysine
nicotinamide + [histone H3]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [histone H4]-N6-acetyl-L-lysine
nicotinamide + [histone H4]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [tumor necrosis factor alpha]-N6-acyl-L-lysine20
nicotinamide + [tumor necrosis factor alpha]-L-lysine20 + 2'-O-acyl-ADP-ribose
show the reaction diagram
-
SIRT6 promotes the secretion of tumor necrosis factor alpha by removing the fatty acyl modification on K19 and K20 of TNFalpha
-
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4R)-1-[(benzyloxy)carbonyl]-4-hydroxy-L-prolyl-N6-ethanethioyl-N-phenyl-L-lysinamide
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0.2 mM, 56% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
1-(tert-butoxycarbonyl)-L-prolyl-N6-ethanethioyl-N-phenyl-L-lysinamide
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0.2 mM, 32% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
-
i.e. EX-527. 0.2 mM, 56% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
methyl N2-acetyl-N6-ethanethioyl-L-lysyl-L-alaninate
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0.2 mM, 20% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N2-[(benzyloxy)carbonyl]-N6-ethanethioyl-N-(2-fluorophenyl)-L-lysinamide
-
0.2 mM, 25% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N2-[(benzyloxy)carbonyl]-N6-ethanethioyl-N-pyridin-3-yl-L-lysinamide
-
0.2 mM, 54% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N2-[(benzyloxy)carbonyl]-N6-ethanethioyl-N-[2-(4-methoxyphenyl)-2-oxoethyl]-L-lysinamide
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0.2 mM, 48% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amino-4-methylcoumarin
N6-ethanethioyl-N-(2-oxo-2-phenylethyl)-N2-(3-phenylpropanoyl)-L-lysinamide
-
0.2 mM, 20% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N6-ethanethioyl-N-phenyl-N2-[3-(pyridin-3-yl)propanoyl]-L-lysinamide
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0.2 mM, 18% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N6-ethanethioyl-N2-(3-phenylpropanoyl)-L-lysyl-L-alanine
-
0.2 mM, 20% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
N6-ethanethioyl-N2-[3-(2-fluorophenyl)propanoyl]-N-pyridin-3-yl-L-lysinamide
-
0.2 mM, 58% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amino-4-methylcoumarin
nicotinamide
-
inhibits the deacetylation of native histones much more effectively than deacetylation of a synthetic substrate
quercetin
-
0.2 mM, 52% inhibition, substrate: Ac-RYQ(N6-acetyl)K-7-amido-4-methylcoumarin
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
the enzyme is unaffected by the activators isonicotinamide and resveratrol
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.22
SKEYFS(N6-acetyl)KQK
-
pH 7.8, 37C
-
0.039 - 0.81
[histone H3 peptide]-N6-acetyl-L-lysine
-
0.008 - 0.2
[histone H3 peptide]-N6-butyryl-L-lysine
-
0.0034
[histone H3 peptide]-N6-myristoyl-L-lysine
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pH 8.0, 37C
-
0.0012 - 0.04
[histone H3 peptide]-N6-octanoyl-L-lysine
-
0.0009
[histone H3 peptide]-N6-palmitoyl-L-lysine
-
pH 8.0, 37C
-
0.0024
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
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pH 8.0, 37C
-
0.0045
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
-
pH 8.0, 37C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001 - 0.0039
[histone H3 peptide]-N6-acetyl-L-lysine
-
0.0021
[histone H3 peptide]-N6-butyryl-L-lysine
Homo sapiens
-
pH 8.0, 37C
-
0.0049 - 0.01
[histone H3 peptide]-N6-myristoyl-L-lysine
-
0.001 - 0.0046
[histone H3 peptide]-N6-octanoyl-L-lysine
-
0.0027
[histone H3 peptide]-N6-palmitoyl-L-lysine
Homo sapiens
-
pH 8.0, 37C
-
0.002
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
Homo sapiens
-
pH 8.0, 37C
-
0.005
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
Homo sapiens
-
pH 8.0, 37C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.132
SKEYFS(N6-acetyl)KQK
Archaeoglobus fulgidus
-
pH 7.8, 37C
197658
0.0048 - 0.026
[histone H3 peptide]-N6-acetyl-L-lysine
197651
0.01 - 0.16
[histone H3 peptide]-N6-butyryl-L-lysine
197652
0.14 - 10
[histone H3 peptide]-N6-myristoyl-L-lysine
197654
0.12 - 0.92
[histone H3 peptide]-N6-octanoyl-L-lysine
197653
3
[histone H3 peptide]-N6-palmitoyl-L-lysine
Homo sapiens
-
pH 8.0, 37C
197655
0.83
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine19
Homo sapiens
-
pH 8.0, 37C
197656
1.1
[synthetic tumor necrosis factor alpha peptide]-N6-myristoyl-L-lysine20
Homo sapiens
-
pH 8.0, 37C
197657
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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muscle invasive urothelial carcinoma of the bladder. Decline of SIRT6 expression when bladder cancer progresses from stage T2 to stage T4
Manually annotated by BRENDA team
-
SIRT6 is down-regulated in human glioma tissues
Manually annotated by BRENDA team
-
epidermal
Manually annotated by BRENDA team
-
SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
SIRT6 translocates into the cytoplasm under stress and regulates formation as well as disassembly of stress granules
Manually annotated by BRENDA team
-
Sirt6 partially colocalizes with mitotic spindles
Manually annotated by BRENDA team
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Sirt6 is enriched in the nucleolus in the G1 phase of the cell cycle, while S phase nucleoli are almost entirely free of Sirt6
Manually annotated by BRENDA team
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SIRT6 activity is nucleosome dependent, and suggest that its binding to the nucleosome might convert it into an active structure
Manually annotated by BRENDA team
-
during interphase, Sirt6 is mostly localized to the nucleus
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystals are grown by hanging drop method, structures of the enzyme bound to nictotinamide are determined from a single crystal diffracting to 2.4 A resolution. The structures show that free nicotinamide binds in a conserved pocket that participates in NAD+ binding and catalysis
-
vapor diffusion at 20C, crystal structure of the enzyme bound to KGLGKGGA(N6-myristoyl)KRHRKW
-
hanging drop vapor diffusion at 20C. Crystal structures in complex with ADP-ribose and the non-hydrolyzable analog of O-acetyl-ADP-ribose, 2'-N-acetyl-ADP-ribose
-
hanging drop vapor diffusion method at 18C, crystal structure of Sirt6 in complex with a histone H3 K9 myristoyl peptide and ADPribose at 2.2 A resolution
-
hanging drop vapor diffusion method, cocrystal of enzyme with [histone H3 peptide]-N6-myristoyl-L-lysine
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli with a C-terminal His6 tag and an N-terminal T7 tag
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expression in Escherichia coli
SIRT6 overexpression in terminally differentiated cortical and hippocampal neurons, mediated by a neuron-specific recombinant adeno-associated virus, downregulates cell viability under oxidative stress condition
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decline of SIRT6 expression when bladder cancer progresses from stage T2 to stage T4
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during mitosis, the Sirt6 expression level is increased
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H2O2 treatment significantly reduces Sirt6 protein. Stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy
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in cortical and hippocampal neurons SIRT6 is downregulated during maturation in vitro, reaching the lowest expression at 11 days in vitro
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SIRT6 is down-regulated in human glioma tissues
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SIRT6 is upregulated in squamous cell carcinoma
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M70R
-
further decrease in nicotinamide sensitivity compared to wild-type
H131Y
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the mutant enzyme can still bind NAD+ but has a decreased ability to bind ADP-ribose
H133Y
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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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine