SIRT6 Protein, Human (His)

SIRT6 is an NAD-dependent protein deacetylase, deacylase, and mono-ADP-ribosyltransferase that plays pivotal roles in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis, and aging. It catalyzes deacetylation of histone H3 at Lys-9, Lys-18, and Lys-56 (H3K9ac, H3K18ac, and H3K56ac), suppressing target gene expression of transcription factors like NF-kappa-B. SIRT6 participates in double-strand break (DSB) repair by binding DSB sites, recruiting repair proteins (e.g., SMARCA5/SNF2H), and deacetylating H3K9ac/H3K56ac (By similar mechanisms potentially linked to lifespan extension). It also promotes DNA repair via deacetylation of non-histone proteins (e.g., DDB2 and p53/TP53). Metabolically, SIRT6 inhibits glycolysis (by repressing HIF1A), regulates gluconeogenesis (via FOXO1/KAT2A deacetylation), and modulates lipid catabolism (by activating PPARA through NCOA2 deacetylation) (By similar roles in brown adipocytes). Its defatty-acylase activity (e.g., demyristoylation/depalmitoylation of RRAS2/TNF) controls protein secretion, while mono-ADP-ribosylation (e.g., of PARP1/TRIM28) contributes to DNA repair and transcriptional regulation.