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3.5.1.- Histone deacetylases (HDACs) C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Histone deacetylases act as erasers of epigenetic acetylation marks on lysine residues in histones. Removal of the acetyl groups facilitates tighter packing of chromatin (heterochromatin formation) leading to transcriptional repression.

The histone deacetylase family has been classified in to five subfamilies based on phylogenetic comparison with yeast homologues:
Class I contains HDACs 1, 2, 3 and 8
Class IIa contains HDACs 4, 5, 7 and 9
Class IIb contains HDACs 6 and 10
Class III contains the sirtuins (SIRT1-7)
Class IV contains only HDAC11.
Classes I, II and IV use Zn+ as a co-factor, whereas catalysis by Class III enzymes requires NAD+ as a co-factor, and members of this subfamily have ADP-ribosylase activity in addition to protein deacetylase function [23].

HDACs have more general protein deacetylase activity, being able to deacetylate lysine residues in non-histone proteins [3] such as microtubules [10], the hsp90 chaperone [13] and the tumour suppressor p53 [16].

Dysregulated HDAC activity has been identified in cancer cells and tumour tissues [14,21], making HDACs attractive molecular targets in the search for novel mechanisms to treat cancer [27]. Several small molecule HDAC inhibitors are already approved for clinical use: romidepsin, belinostat, vorinostat, panobinostat, belinostat, valproic acid and tucidinostat. HDACs and HDAC inhibitors currently in development as potential anti-cancer therapeutics are reviewed by Simó-Riudalbas and Esteller (2015) [24].

Enzymes

2712
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histone deacetylase 1 Show summary » More detailed page go icon to follow link

histone deacetylase 2 Show summary » More detailed page go icon to follow link

histone deacetylase 3 Show summary » More detailed page go icon to follow link

histone deacetylase 4 Show summary » More detailed page go icon to follow link

histone deacetylase 5 Show summary » More detailed page go icon to follow link

histone deacetylase 6 C Show summary » More detailed page go icon to follow link

histone deacetylase 7 Show summary » More detailed page go icon to follow link

histone deacetylase 8 Show summary » More detailed page go icon to follow link

histone deacetylase 9 Show summary » More detailed page go icon to follow link

histone deacetylase 10 Show summary » More detailed page go icon to follow link

histone deacetylase 11 Show summary » More detailed page go icon to follow link

sirtuin 1 Show summary » More detailed page go icon to follow link

sirtuin 2 Show summary » More detailed page go icon to follow link

sirtuin 3 Show summary »

sirtuin 4 Show summary »

sirtuin 5 Show summary »

sirtuin 6 Show summary »


Target Id 2712
Nomenclature sirtuin 6
Genes SIRT6 (Hs), Sirt6 (Mm), Sirt6 (Rn)
Ensembl ID ENSG00000077463 (Hs), ENSMUSG00000034748 (Mm), ENSRNOG00000006393 (Rn)
UniProtKB AC Q8N6T7 (Hs), P59941 (Mm)
EC number
2.4.2.31
Inhibitors
AKK(thioAc)LM21 pIC50 4.3 [12]
Allosteric modulators
MDL-800 (Binding) pKd 5.3 [9]
MDL-800 (Activation) pEC50 5.0 [9]
Comment SIRT6 plays a central role in cellular homeostasis. Small molecule SIRT6 modulators is being investigated for pharmaceutical potential in a range of diseases including cancer and age-related disorders [8].

sirtuin 7 Show summary »

Further reading

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References

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How to cite this family page

Database page citation:

3.5.1.- Histone deacetylases (HDACs). Accessed on 05/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=848.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.