Table 1.
SIRTs family genes: localization, substrates, functions, and modulators.
| Type (Class) |
Localization (Mol. Weight) |
Tissue Expression | Enzyme Activity | Substrates | Functions | Activators | Inhibitors |
|---|---|---|---|---|---|---|---|
| SIRT1 (I) |
Nuclear; cytosolic. (81.7 kDa) |
Brain; Skeletal muscle; Heart; Kidney; Uterus. | NAD+-dependent deacetylases catalyze the deacetylation of histones and nonhistone proteins. | Acetyl-CoA synthetase 1;Akt; Androgene receptor; APE1; Atg 5; Atg 7; Atg 8; BCL6; BMAL1; c-MYC; cortactin; CRABPII; CRTC2; DNMT1; eNOS; FOXA2; FOXO family; FXR; HIF1α; HIF2α; Histone H1K26; Histone H3K9; Histone H4K16; Histone K14; Histone K56; HIV Tat; HMGB1; HMGCS1; hMOF; HSF1; IRF-1; KAP1; KDAC1; Ku70; LKB1; LXR; MEF2; NBS1; NF-κB(p65); Notch1; p300; p53; p73; PARP1; PCAF; PER2; PGAM1; PGC1α; PML; PPAR-γ; RFX-5; SATB1; Smad7; SREBP-1c; SUV39H1; TDG; TFAM; TIP60; TopBP1; TORC1; UCP2; WRN; XPA. | Apoptosis; Cell cycle; Cell migration; Cell survival; Circadian control; Inflammation; Insulin signaling; Lifespan regulation; Metabolism regulation; Neuroprotection; Oxidative stress response; Mitohormesis; Tumor suppression; Viral transcription. |
Resveratrol; Piceatannol; Quercetin; Fisetin; Daidzein; Genistein; Berberine; Flavonoid mulberrin; The xanthone gartanin; The alkaloids quinidine and quinine. | Tanikolide dimer; Chalcones; Biochalcones. |
| SIRT2 (I) |
Nuclear; cytosolic. (41.5 kDa) |
Brain. | NAD+-dependent HDAC and ADP-ribosyl transferase activities. |
Akt; ALDH1A1; APCCDH1; ATRIP; BubR1; CDC20; CDK9; FOXO1; FOXO3a; G6PD; H4K16; HIF1α; Histone H3K18; Histone H3K56; Histone H4K16; K-RAS; NF-κB (p65); p300; p53; Par-3; PEPCK1; PGAM; TUG; α-tubulin; β-secretase 1. | Adipocyte differentiation; Autophagy; Bacterial infections; Cell cycle regulation; Energy homeostasis Fibrosis; Genome stability; Immune response; Longevity; Myelination; Neurodegeneration. |
Resveratrol. | Tanikolide dimer. |
| SIRT3 (I) |
Mitochondrial; Nuclear. (43.6 kDa) |
Brain; Heart; Liver; Kidney; Brown adipose tissue. | NAD+-dependent deacetylases catalyze the deacetylation of histones and nonhistone proteins. | Acetyl-CoA synthetase 2; Aconitase 2; ALDH2; ATP-synthase F1; Complex 1; Cyclophilin D; FOXO3a; GDH; GOT2; GSK3β; Histone H4K16; HMGCS2; Hsp10; Long-chain acyl-CoA dehydrogenase; HMGCS; Isocitrate dehydrogenase 2; Ku70; LCAD; LKB1; MDH; Mitochondrial ribosomal protein L10; MnSOD; OGG1; OPA1; OTC; PDH; PGC-1α; SDH; Skp2; SOD2; UCP-1; VLCAD. | Fatty acid oxidation; Fibrosis; Longevity; Metabolism regulation; Oxidative phosphorylation; Oxidative stress TCA cycle; Thermogenesis; Urea cycle. |
Resveratrol; Trans-(−)-ε-viniferin; Piceatannol. | - |
| SIRT4 (II) |
Mitochondrial (35.2 kDa) |
Brain; Liver; Kidney; Heart; Pancreatic β-cells. | NAD+-dependent HDAC and ADP-ribosyl transferase activities. |
ANT2/3; GDH; Hsp60; MCD; Pyruvate dehydrogenase complex; Stress-70. |
Fatty acid oxidation; Insulin secretion; Metabolism regulation; TCA cycle; Tumor suppression. | - | |
| SIRT5 (III) |
Mitochondrial; Nuclear (33.9 kDa) |
Brain; Heart; Muscle; Testis; Lymphoblast. | NAD+-dependent deacetylases catalyze the deacetylation of histones; Desuccinylase; Demalonylase; Deglutarylase. | Cytochrome c; Carbamoyl phosphate; GAPDH; HMGCS2; Hsp70; IDH; PML; Prx-1; SOD1; Synthetase 1; UOX; VLCAD. | Apoptosis; Fatty acid oxidation; Ketone body synthesis; Oxidative stress; Urea cycle. | Resveratrol; Piceatannol. | - |
| SIRT6 (IV) |
Nuclear (39.1 kDa) |
Brain; Heart; Muscles; Ovaries; Bone cells. | NAD+-dependent ADP ribosyltransferase (ART) mediating mitochondrial protein ribosylation; Demyristoylase; Depalmitoylase. | GCN5; Histone H3K9; Histone H3K56; H3k18ac; TNF-α; KAP1; NF-κB; p70; PAPR1. | Apoptosis; DNA repair; Genome stability; Longevity; Protein secretion. | Anthocyanidins; Gallic acid derivatives. | Catechins; Epicatechins; Phytoestrogens. |
| SIRT7 (IV) |
Nucleolus; Cytoplasm (44.9 kDa) |
Peripheral blood cells; CD33+ myeloid bone marrow precursor cells. | NAD+ dependent deacetylase; Desuccinylase; Regulates the RNA polymerase I (Pol I) transcriptional machinery. | DNA-PK; GABPβ1; Histone H3K122; Histone H3K18; H3K36ac; p53; PAF53; RNA polymerase I; U3–55k. | Cell cycle regulation; Genome stability; Regulation of rDNA transcription; Tumor promotion. | - |