Cloned (Comment) | Organism |
---|---|
gene SIRT6, recombinant overexpression of wild-type SIRT6 and catalytically inactive SIRT6 mutant H133Y using retroviral transduction in BxPC-3 and MCF-7 cells | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | knockdown of SIRT6 in HepG2 cells | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
intracellular | - |
Homo sapiens | 5622 | - |
nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | acetylation of nicotinamide phosphoribosyltransferase, i.e. NAMPT, on residue K53 by SIRT6 | ? | - |
- |
|
NAD+ + [protein]-N6-palmitoyl-L-lysine | Homo sapiens | - |
nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8N6T7 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
BxPC-3 cell | - |
Homo sapiens | - |
carcinoma cell | - |
Homo sapiens | - |
Hep-G2 cell | - |
Homo sapiens | - |
kidney | - |
Homo sapiens | - |
liver | - |
Homo sapiens | - |
lung | - |
Homo sapiens | - |
MCF-7 cell | - |
Homo sapiens | - |
additional information | SIRT6 expression levels regulate NAD+ levels in different organs | Homo sapiens | - |
pancreas | - |
Homo sapiens | - |
spleen | - |
Homo sapiens | - |
white adipose tissue | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | acetylation of nicotinamide phosphoribosyltransferase, i.e. NAMPT, on residue K53 by SIRT6 | Homo sapiens | ? | - |
- |
|
NAD+ + [protein]-N6-palmitoyl-L-lysine | - |
Homo sapiens | nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Synonyms | Comment | Organism |
---|---|---|
SIRT6 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | in SIRT6-overexpressing cells, NAD(H) levels are upregulated, as a consequence of NAMPT activation | Homo sapiens |
physiological function | in gastrointestinal tumors, SIRT6 acts as a tumor suppressor, through different mechanisms, which include its ability to prevent the Warburg effect and genomic instability. In other types of tumors, including multiple myeloma and skin squamous cell carcinoma, high SIRT6 expression is associated with poor clinical outcome and may act pro-oncogenically. SIRT6 is involved in the regulation of a wide number of metabolic processes. SIRT6 deacetylase activity regulates the activity of NAD(P)(H) pools and nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage pathway from nicotinamide, in cancer cells. By controlling the biosynthesis of NAD+, NAMPT regulates the activity of NAD+-converting enzymes, such as CD38, poly-ADP-ribosepolymerases, and sirtuins (SIRTs). SIRT6 expression modulates the intracellular NADP(H) levels and G6PD activity. SIRT6 expression levels regulate NAD+ levels in different organs. SIRT6 regulates eNAMPT secretion. NAMPT is a direct substrate of SIRT6 deacetylation, with a mechanism that upregulates NAMPT enzymatic activity. SIRT6 affects intracellular NAMPT activity, boosts NAD(P)(H) levels, and protects against oxidative stress. In cancer, SIRT6 has been reported to play a context-dependent role. K53 is a key residue responsible for SIRT6-mediated upregulation of NAMPT activity, while K79 does not seem to be involved in SIRT6-mediated regulation of NAMPT enzymatic activity | Homo sapiens |