Crystallization (Comment) | Organism |
---|---|
analysis of in silico cocrystal structure of SIRT6 bound to ADP-ribose and a H3K9 myristoylated peptide, PDB ID 3ZG6 | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
D63H | naturally occuring mutation in SIRT6, the homozygous inactivating mutation of histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses, it causes human perinatal lethality, missense mutation SIRT6 p.D63H in affected fetal amniocytes. SIRT6 D63H mutant mESCs fail to form EBs and retain pluripotent gene expression. The amino acid change at Asp63 to a histidine results in virtually complete loss of H3K9 deacetylase and demyristoylase functions. Asp63 is located in the NAD+-binding pocket, forming hydrogen bonds with neighboring amino acids and thus providing structure to the NAD+-binding loop | Homo sapiens |
D63H | naturally occuring mutation in SIRT6, the homozygous inactivating mutation of histone deacetylase SIRT6. Asp63 is located in the NAD+-binding pocket, forming hydrogen bonds with neighboring amino acids and thus providing structure to the NAD+-binding loop | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
NAD+ + [protein]-N6-palmitoyl-L-lysine | Homo sapiens | - |
nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [protein]-N6-palmitoyl-L-lysine | Mus musculus | - |
nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8N6T7 | - |
- |
Mus musculus | P59941 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
cardiac muscle fiber | - |
Homo sapiens | - |
cardiac muscle fiber | - |
Mus musculus | - |
embryoid body | - |
Homo sapiens | - |
embryonic stem cell | - |
Homo sapiens | - |
embryonic stem cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
NAD+ + [protein]-N6-palmitoyl-L-lysine | - |
Homo sapiens | nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? | |
NAD+ + [protein]-N6-palmitoyl-L-lysine | - |
Mus musculus | nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose | - |
? |
Synonyms | Comment | Organism |
---|---|---|
histone deacetylase | - |
Homo sapiens |
histone deacetylase | - |
Mus musculus |
SIRT6 | - |
Homo sapiens |
SIRT6 | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NAD+ | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | an inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality. The homozygous inactivating mutation D63H in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses. Human induced pluripotent stem cells (iPSCs) derived from D63H homozygous fetuses fail to differentiate into embryoid bodies (EBs), functional cardiomyocytes, and neural progenitor cells due to a failure to repress pluripotent genes. SIRT6 knockout ESCs cultured to form EBs are significantly smaller than their wild-type counterparts. SIRT6 D63H mutant mESCs fail to differentiate into functional cardiomyocyte foci. SIRT6 D63H mutant cardiomyocytes fail to suppress HAND1 expression while exhibiting significantly reduced FBN1 levels when compared with SIRT6 knockout cells | Homo sapiens |
malfunction | functionally, SIRT6 D63H mouse embryonic stem cells (mESCs) fail to repress pluripotent gene expression, direct targets of SIRT6, and exhibit an even more severe phenotype than Sirt6-deficient ESCs when differentiated into embryoid bodies (EBs). When terminally differentiated toward cardiomyocyte lineage, D63H mutant mESCs maintain expression of pluripotent genes and fail to form functional cardiomyocyte foci | Mus musculus |