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Literature summary for 2.3.1.B43 extracted from
- NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65 (2017), J. Autoimmun., 81, 120-129 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene SIRT5, transient overexpression of wild-type and mutant enzymes in HEK-293T cells or RAW-264.7 cells | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| H158Y | site-directed mutagenesis, like the wild-type enzyme, mutant SIRT5-H158Y overexpression significantly increases secondary LPS stimulation-induced interleukin-6 and TNF-alpha production in RAW264.7 cells | Mus musculus |
| additional information | knockdown of SIRT5 expression in macrophages using siRNA | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Mus musculus | 5737 | - |
| mitochondrion | - |
Mus musculus | 5739 | - |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mus musculus | Q8K2C6 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| liver | - |
Mus musculus | - |
| lung | - |
Mus musculus | - |
| macrophage | SIRT5 and SIRT1/2 have opposite expression patterns and functions in macrophages, overview | Mus musculus | - |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| NAD+ dependent deacetylase | - |
Mus musculus |
| sirtuin 5 | - |
Mus musculus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NAD+ | - |
Mus musculus |  |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Mus musculus | decreased expression of SIRT5 is found in cultured macrophages upon primary or second LPS stimulation | down |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | SIRT5 deficiency decreases TLR-triggered inflammation in both acute and immunosuppressive phases of sepsis. Acetylation of p65 K310 is impaired in SIRT5-/- peritoneal macrophages upon TLR4 activation. The p65 overexpression-induced NF-kappaB reporter activity is significantly increased by SIRT5 overexpression, but impaired by SIRT1/2 overexpression in HEK-293T cells. Decreased expression of SIRT5 is found in cultured macrophages upon primary or second LPS stimulation | Mus musculus |
| metabolism | function of sirtuin family members in the inflammatory responses, overview. SIRT5 and SIRT1/2 have opposite expression patterns and functions in macrophages. Cytoplasmic SIRT5 counteracts the inhibitory effects of SIRT2 and enhances the innate inflammatory responses in macrophages and even in endotoxin-tolerant macrophages by promoting acetylation of p65 and activation of NF-kappaB pathway. Mechanistically, SIRT5 competes with SIRT2 to interact with NF-kappaB p65, in a deacetylase activity-independent way, to block the deacetylation of p65 by SIRT2, which consequently leads to increased acetylation of p65 and the activation of NF-kB pathway and its downstream cytokines | Mus musculus |
| physiological function | SIRT5 enhances acetylation (K310) of NF-kappaB p65 in response to innate stimuli. SIRT5 enhances acetylation of p65 by blocking p65 interaction of SIRT2. Endogenous SIRT5 interacts with p65 in the cytoplasm of macrophages. SIRT5 rescues hypo-inflammatory response in endotoxin-tolerant macrophages | Mus musculus |
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Release 2023.1 (January 2023)
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