Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748, PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:10748112, PubMed:10922473, PubMed:10926844, PubMed:14701748). Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin (PubMed:22885700). May play a role in smooth muscle cell contractility (PubMed:15772115). In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones (PubMed:28497810). H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-[histone] H2O + N(6)-acetyl-L-lysyl-[protein] = acetate + L-lysyl-[protein] H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate + L-lysyl-[protein] Binds 1 divalent metal cation per subunit. Its activity is inhibited by trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), 3-(1-methyl-4-phenylacetyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamide (APHA), 4-dimethylamino-N-(6-hydroxycarbamoyethyl)benzamide-N-hydroxy-7-(4-dimethylaminobenzoyl)aminoheptanamide (MS-344), 5-(4-methyl-benzoylamino)-biphenyl-3,4'-dicarboxylic acid 3-dimethylamide 4'-hydroxyamide (CRA-A) and butyrate. Interacts with PEPB2-MYH11, a fusion protein consisting of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11 produced by the inversion Inv(16)(p13q22), a translocation associated with acute myeloid leukemia of M4EO subtype (PubMed:12509458). The PEPB2-MYH1 fusion protein also interacts with RUNX1, a well known transcriptional regulator, suggesting that the interaction with HDAC8 may participate in the conversion of RUNX1 into a constitutive transcriptional repressor (PubMed:12509458). Interacts with CBFA2T3 (PubMed:11533236). Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation (PubMed:16809764). Associates with alpha-SMA (smooth muscle alpha-actin) (PubMed:15772115). Excluded from the nucleoli (PubMed:10748112). Found in the cytoplasm of cells showing smooth muscle differentiation (PubMed:15772115, PubMed:16538051). Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney. Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4. The disease is caused by variants affecting the gene represented in this entry. Belongs to the histone deacetylase family. HD type 1 subfamily. Aberrant splicing.