Literature summary for 2.3.1.B41 extracted from

Pan, H.; Guan, Di; Liu, X.; Li, J.; Wang, L.; Wu5, J.; Zhou1, J.; Zhang, W.; Ren, R.; Zhang, W.; Li, Y.; Yang, J.; Hao, Y.; Yuan, T.; Yuan, G.; Wang, H.; Ju, Z.; Mao, Z.; Li, J.; Qu, J.; Tang, F.; Liu, G.-H.
SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2 (2016), Cell Res., 26, 190-205 .

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Protein Variants

Protein Variants	Comment	Organism
H133Y	inactive enzyme mutant	Homo sapiens
additional information	generation of SIRT6 knockout human mesenchymal stem cells (hMSCs) by targeted gene editing. For generation of SIRT6-deficient human embryonic stem cells (hESCs), the exon 1 of SIRT6 gene is removed in hESCs by a transcription activator-like effector nuclease. SIRT6-deficient hMSCs exhibit accelerated functional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs are predominately characterized by dysregulated redox metabolism and increased sensitivity to the oxidative stress. SIRT6 forms a protein complex with both nuclear factor erythroid 2-related factor 2 (NRF2) and RNA polymerase II, which is required for the transactivation of NRF2-regulated antioxidant genes, including heme oxygenase 1 (HO-1). Phenotype, overview	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q8N6T7	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
embryonic stem cell	-	Homo sapiens	-
mesenchymal stem cell	-	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
SIRT6	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
NAD+	-	Homo sapiens

General Information

General Information	Comment	Organism
evolution	SIRT6 belongs to the mammalian homologues of Sir2 histone NAD+-dependent deacylase family	Homo sapiens
malfunction	SIRT6 knockout human mesenchymal stem cells (hMSCs) exhibit accelerated functional decay, a feature distinct from typical premature cellular senescence. Rather than compromised chromosomal stability, SIRT6-null hMSCs are predominately characterized by dysregulated redox metabolism and increased sensitivity to the oxidative stress. SIRT6 forms a protein complex with both nuclear factor erythroid 2-related factor 2 (NRF2) and RNA polymerase II, which is required for the transactivation of NRF2-regulated antioxidant genes, including heme oxygenase 1 (HO-1). Overexpression of HO-1 in SIRT6 null hMSCs rescues premature cellular attrition. SIRT6-/- hMSCs are susceptible to oxidative stress. Reintroduction of wild-type SIRT6, but not of the H133Y mutant into SIRT6-/- hMSCs repress accelerated cellular senescence	Homo sapiens
physiological function	SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Function of SIRT6 in maintaining hMSC homeostasis by serving as a NRF2 coactivator, which represents another layer of regulation of oxidative stress-associated stem cell decay. SIRT6 is required for NRF2-depedent HO-1 expression in human mesenchymal stem cells (hMSCs)	Homo sapiens

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Release 2023.1 (January 2023)