Function: NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins such as ACLY, PCK1 and RELA. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA. Ref.12 Ref.13 Ref.20 Ref.21 Ref.22
Catalytic activity: NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.11
Cofactor: Binds 1 zinc ion per subunit.
Enzyme regulation: Inhibited by Sirtinol, A3 and M15 small molecules. Inhibited by nicotinamide.
Subunit structure: Interacts with HDAC6, suggesting that these proteins belong to a large complex that deacetylate the cytoskeleton. Ref.12
Subcellular location: Cytoplasm › cytoskeleton. Note: Colocalizes with microtubules. Ref.2 Ref.12 Ref.15
Tissue specificity: Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network. Ref.1 Ref.2 Ref.14
Developmental stage: Peaks during mitosis. After mitosis, it is probably degraded by the 26S proteasome. Ref.13
Post-translational modification: Phosphorylated at the G2/M transition of the cell cycle. Ref.13
Miscellaneous: Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo.
Sequence similarities: Belongs to the sirtuin family. Class I subfamily.Contains 1 deacetylase sirtuin-type domain.
Sequence caution: The sequence AAD45971.1 differs from that shown. Reason: Erroneous initiation. The sequence AAF67015.1 differs from that shown. Reason: Frameshift at several positions.
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