Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | binding of free fatty acids to SIRT6 significantly enhances SIRT6's in vitro histone deacetylase activity | Mus musculus | |
additional information | binding of free fatty acids to SIRT6 significantly enhances SIRT6's in vitro histone deacetylase activity. Given Sirt6 critical roles in multiple molecular pathways, including DNA repair, telomere maintenance, glycolysis, gluconeogenesis, lipid metabolism, inflammation, and tumor suppression, it is clear that attempts to enhance the activity of SIRT6 could provide therapeutic benefits, development of SIRT6 activators, overview | Homo sapiens |
Application | Comment | Organism |
---|---|---|
medicine | the enzyme is a potential therapeutic target for therapy of cancer and other metabolic diseases | Homo sapiens |
medicine | the enzyme is a potential therapeutic target for therapy of cancer and other metabolic diseases | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
nucleus | - |
Homo sapiens | 5634 | - |
nucleus | - |
Mus musculus | 5634 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Mus musculus | SIRT6 is a specific deacetylase for H3K9, see EC 2.3.1.286. It also deacetylates H3K56 and H3K18, as well as KAP1, CtIP, PGC-1alpha, TRF2, GCN5, SNF2H, and PKM2 | ? | - |
- |
|
additional information | Homo sapiens | SIRT6 is a specific deacetylase for H3K9, see EC 2.3.1.286. It also deacetylates H3K56 and H3K18, as well as KAP1, CtIP, PGC-1alpha, TRF2, GCN5, SNF2H, and PKM2, cf. EC 2.3.1.286 | ? | - |
- |
|
NAD+ + [protein]-N6-palmitoyl-L-lysine | Homo sapiens | - |
nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [protein]-N6-palmitoyl-L-lysine | Mus musculus | - |
nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [TNF-alpha]-N6-palmitoyl-L-lysine | Homo sapiens | - |
nicotinamide + [TNF-alpha]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [TNF-alpha]-N6-palmitoyl-L-lysine | Mus musculus | - |
nicotinamide + [TNF-alpha]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8N6T7 | - |
- |
Mus musculus | P59941 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
additional information | SIRT6 SUMOylation appears to specifically regulate SIRT6 deacetylation on H3K56 but not H3K9 | Homo sapiens |
additional information | SIRT6 SUMOylation appears to specifically regulate SIRT6 deacetylation on H3K56 but not H3K9 | Mus musculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
embryo | - |
Mus musculus | - |
neural stem cell | - |
Homo sapiens | - |
neural stem cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | SIRT6 is a specific deacetylase for H3K9, see EC 2.3.1.286. It also deacetylates H3K56 and H3K18, as well as KAP1, CtIP, PGC-1alpha, TRF2, GCN5, SNF2H, and PKM2 | Mus musculus | ? | - |
- |
|
additional information | SIRT6 is a specific deacetylase for H3K9, see EC 2.3.1.286. It also deacetylates H3K56 and H3K18, as well as KAP1, CtIP, PGC-1alpha, TRF2, GCN5, SNF2H, and PKM2, cf. EC 2.3.1.286 | Homo sapiens | ? | - |
- |
|
additional information | SIRT6 can undergo intramolecular mono-ADP-ribosylation utilizing NAD+ as a substrate, i.e. mono-ADP-ribosylation. SIRT6 also performs ADP-ribosyl transferase activity on other protein substrates, overview. Weak deacetylase activity of SIRT6 in vitro | Homo sapiens | ? | - |
- |
|
additional information | SIRT6 can undergo intramolecular mono-ADP-ribosylation utilizing NAD+ as a substrate. Purified mouse SIRT6 successfully catalyzes the transfer of radiolabel from [32P]NAD+ onto itself, i.e. mono-ADP-ribosylation. also performs ADP-ribosyl transferase activity on other protein substrates, overview. Weak deacetylase activity of SIRT6 in vitro | Mus musculus | ? | - |
- |
|
NAD+ + [protein]-N6-palmitoyl-L-lysine | - |
Homo sapiens | nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [protein]-N6-palmitoyl-L-lysine | - |
Mus musculus | nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [TNF-alpha]-N6-palmitoyl-L-lysine | - |
Homo sapiens | nicotinamide + [TNF-alpha]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [TNF-alpha]-N6-palmitoyl-L-lysine | - |
Mus musculus | nicotinamide + [TNF-alpha]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ADP-ribosyl transferase | - |
Homo sapiens |
ADP-ribosyl transferase | - |
Mus musculus |
chromatin deacylase | - |
Homo sapiens |
chromatin deacylase | - |
Mus musculus |
deacylase | - |
Homo sapiens |
deacylase | - |
Mus musculus |
histone deacetylase | - |
Homo sapiens |
histone deacetylase | - |
Mus musculus |
More | see also EC 2.3.1.286 | Homo sapiens |
More | see also EC 2.3.1.286 | Mus musculus |
SIRT6 | - |
Homo sapiens |
SIRT6 | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NAD+ | - |
Mus musculus |
Organism | Comment | Expression |
---|---|---|
Mus musculus | several factors regulate the expression of the SIRT6 gene. PARP1 may inhibit the expression of SIRT6, and the presence of PJ-34, a PARP1 inhibitor, results in enhanced mRNA level of nuclear SIRT6. A role for the transcription factor E2F1 as an enhancer of glycolysis and inhibitor of the expression of SIRT6. E2F1 directly binds the SIRT6 promoter and suppresses SIRT6 promoter activity under both normoxic and hypoxic culture conditions. In embryos and neural stem cells, SIRT6 expression becomes suppressed by maternal diabetes in vivo or high glucose in vitro through oxidative stress | down |
Homo sapiens | several factors regulate the expression of the SIRT6 gene. PARP1 may inhibit the expression of SIRT6, and the presence of PJ-34, a PARP1 inhibitor, results in enhanced mRNA level of nuclear SIRT6. A role for the transcription factor E2F1 as an enhancer of glycolysis and inhibitor of the expression of SIRT6. E2F1 directly binds the SIRT6 promoter and suppresses SIRT6 promoter activity under both normoxic and hypoxic culture conditions. In neural stem cells, SIRT6 expression becomes suppressed by maternal diabetes in vivo or high glucose in vitro through oxidative stress | down |
Homo sapiens | several factors regulate the expression of the SIRT6 gene. Notably, in a tumor-suppressing pathway, c-FOS binds to an AP-1 binding site (TAAGTCA) at the SIRT6 promoter, activating SIRT6 gene expression. In addition to the positive regulators of SIRT6, various chromatin factors negatively control the gene expression of SIRT6. presence of PJ-34, a PARP1 inhibitor, results in enhanced mRNA level of nuclear SIRT6 | up |
Mus musculus | several factors regulate the expression of the SIRT6 gene. Notably, in a tumor-suppressing pathway, c-FOS binds to an AP-1 binding site (TAAGTCA) at the SIRT6 promoter, activating SIRT6 gene expression. In addition to the positive regulators of SIRT6, various chromatin factors negatively control the gene expression of SIRT6. presence of PJ-34, a PARP1 inhibitor, results in enhanced mRNA level of nuclear SIRT6 | up |
General Information | Comment | Organism |
---|---|---|
metabolism | fatty acids and SIRT6 regulation, overview. Nucleosome structure may as well modulate SIRT6 activity. Role of SIRT6 metabolic homeostasis, cellular metabolism and metabolic diseases, and protein networks, detailed overview. Regulation in cancer, stress response, senescence, and aging | Homo sapiens |
metabolism | fatty acids and SIRT6 regulation, overview. Nucleosome structure may as well modulate SIRT6 activity. Role of SIRT6 metabolic homeostasis, cellular metabolism and metabolic diseases, and protein networks, detailed overview. Regulation in cancer, stress response, senescence, and aging | Mus musculus |
additional information | the extended NH2-terminal loop of SIRT6 covers the NAD+- and acyl-substrate binding sites | Homo sapiens |
additional information | the extended NH2-terminal loop of SIRT6 covers the NAD+- and acyl-substratebinding sites | Mus musculus |
physiological function | enzyme SIRT6 evolved in eukaryotes to perform multiple critical roles in modulating gene expression, metabolism, DNA repair, and lifespan. In this context, SIRT6 plays key roles as a tumor suppressor and a critical modulator of metabolic homeostasis. SIRT6 accomplishes the transfer of radiolabel from [32P]NAD+ through an intramolecular mechanism, suggesting that SIRT6 may utilize ADP-ribosylation as a method to autoregulate its own activity. By modulating H3K9 acetylation, SIRT6 appears to act as a co-repressor of transcription factors, such as nuclear factor kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha). The removal of H3K9 acetylation by SIRT6 helps to regulate telomeric chromatin and gene expression. The role of SIRT6 as a protein deacetylase seems to expand beyond histone proteins. In fact, SIRT6 can directly remove acetyl groups from non-histone proteins. For instance, SIRT6 regulates hepatic glucose production by deacetylating the K549 residue of histone acetyltransferase (HAT) GCN5 and promoting its enzymatic activity. SIRT6 can also deacetylate pyruvate kinase M2 (PKM2) at K433 residue, driving its nuclear export and suppressing PKM2 oncogenic functions. In addition to its NAD+-dependent deacetylation and ADP-ribosylation activity, SIRT6 is also able to catalyze long-chain fatty deacylation, acting as a deacylase of tumor necrosis factor-alpha (TNF-alpha) and multiple secreted proteins. SIRT6 contains a large hydrophobic pocket that may favorably interact with long-chain fatty acyl groups, such as myristoyl. Interaction with these long-chain fatty acyl groups may serve as a regulatory step to modulate the histone deacetylase activity of SIRT6. Regulation of SIRT6 in mammalian cells, SIRT6 has functions in DNA repair, gene expression, telomeric maintenance, mitosis and meiosis, and protein networks, detailed overview | Homo sapiens |
physiological function | enzyme SIRT6 evolved in eukaryotes to perform multiple critical roles in modulating gene expression, metabolism, DNA repair, and lifespan. In this context, SIRT6 plays key roles as a tumor suppressor and a critical modulator of metabolic homeostasis. SIRT6 accomplishes the transfer of radiolabel from [32P]NAD+ through an intramolecular mechanism, suggesting that SIRT6 may utilize ADP-ribosylation as a method to autoregulate its own activity. SIRT6 catalyzes ADP-ribosylation at K521 residue of PARP1 to promote DSB repair under oxidative stress. such as nuclear factor kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha). The removal of H3K9 acetylation by SIRT6 helps to regulate telomeric chromatin and gene expression. The role of SIRT6 as a protein deacetylase seems to expand beyond histone proteins. In fact, SIRT6 can directly remove acetyl groups from non-histone proteins. For instance, SIRT6 regulates hepatic glucose production by deacetylating the K549 residue of histone acetyltransferase (HAT) GCN5 and promoting its enzymatic activity. SIRT6 can also deacetylate pyruvate kinase M2 (PKM2) at K433 residue, driving its nuclear export and suppressing PKM2 oncogenic functions. In addition to its NAD+-dependent deacetylation and ADP-ribosylation activity, SIRT6 is also able to catalyze long-chain fatty deacylation, acting as a deacylase of tumor necrosis factor-alpha (TNF-alpha) and multiple secreted proteins. SIRT6 contains a large hydrophobic pocket that may favorably interact with long-chain fatty acyl groups, such as myristoyl. Interaction with these long-chain fatty acyl groups may serve as a regulatory step to modulate the histone deacetylase activity of SIRT6. Regulation of SIRT6 in mammalian cells, SIRT6 has functions in DNA repair, gene expression, telomeric maintenance, mitosis and meiosis, and protein networks, detailed overview | Mus musculus |