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Literature summary extracted from

  • Ferrer, C.; Alders, M.; Postma, A.; Park, S.; Klein, M.; Cetinbas, M.; Pajkrt, E.; Glas, A.; van Koningsbruggen, S.; Christoffels, V.; Mannens, M.; Knegt, L.; Etchegaray, J.; Sadreyev, R.; Denu, J.; Mostoslavsky, G.; van Maarle, M.; Mostoslavsky, R.
    An inactivating mutation in the histone deacetylase SIRT6 causes human perinatal lethality (2018), Genes Dev., 32, 373-388 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.3.1.B41 analysis of in silico cocrystal structure of SIRT6 bound to ADP-ribose and a H3K9 myristoylated peptide, PDB ID 3ZG6 Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.B41 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
2.3.1.B41 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/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine Homo sapiens
-
 nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine Mus musculus
-
 nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.B41 Homo sapiens Q8N6T7
-
-
2.3.1.B41 Mus musculus P59941
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.1.B41 cardiac muscle fiber
-
 Homo sapiens
-
2.3.1.B41 cardiac muscle fiber
-
 Mus musculus
-
2.3.1.B41 embryoid body
-
 Homo sapiens
-
2.3.1.B41 embryonic stem cell
-
 Homo sapiens
-
2.3.1.B41 embryonic stem cell
-
 Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine
-
 Homo sapiens nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?
2.3.1.B41 NAD+ + [protein]-N6-palmitoyl-L-lysine
-
 Mus musculus nicotinamide + [protein]-L-lysine + 2'-O-palmitoyl-ADP ribose
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.B41 histone deacetylase
-
 Homo sapiens
2.3.1.B41 histone deacetylase
-
 Mus musculus
2.3.1.B41 SIRT6
-
 Homo sapiens
2.3.1.B41 SIRT6
-
 Mus musculus

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.B41 NAD+
-
 Homo sapiens
2.3.1.B41 NAD+
-
 Mus musculus

General Information

EC Number General Information Comment Organism
2.3.1.B41 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
2.3.1.B41 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