Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:23911289, PubMed:30279482). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:23911289). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:19204783). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (By similarity). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (PubMed:26776516). During the activation phase, promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1 (PubMed:26776516). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (PubMed:19037247). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (By similarity). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (By similarity). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (By similarity). In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:30279482). Catalyzes decrotonylation of MAPRE1/EB1 (By similarity). 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] H2O + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein] Interacts with HDAC7 and HDAC9 (PubMed:10984530, PubMed:11022042, PubMed:15711539). Interacts with DAXX, KDM4A, HDAC10 and DACH1 (PubMed:12130660). Found in a complex with NCOR1 and NCOR2 (By similarity). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (By similarity). Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY (PubMed:16537907). Interacts with BTBD14B (By similarity). Interacts with GLIS2 (PubMed:16326862). Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:19204783). Component of the Notch corepressor complex (By similarity). Interacts with CBFA2T3 and NKAP (PubMed:11533236). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (By similarity). Interacts with ZMYND15 (PubMed:20675388). Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements (By similarity). Interacts with INSM1 (By similarity). Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (By similarity). Interacts (via C-terminus) with CCAR2 (via N-terminus) (By similarity). Interacts with and deacetylates MEF2D (By similarity). Interacts with BEND3 (By similarity). Interacts with NKAPL (PubMed:25875095). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (By similarity). Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3 (PubMed:26776516). Interacts with FBXL3 and ARNTL/BMAL1 (PubMed:26776516). Interacts with NCOR1 (PubMed:19037247). Interacts with RARA (By similarity). Interacts with SETD5 (PubMed:30455454). Colocalizes with XBP1 and AKT1 in the cytoplasm. Predominantly expressed in the nucleus in the presence of CCAR2 (By similarity). Sumoylated in vitro. Liver-specific knockout mice exhibit low amplitude of circadian rhythms, dampened E-box-driven transcription and a significant reduction in the protein levels of ARNTL/BMAL1 and CRY1 in the liver. Belongs to the histone deacetylase family. HD type 1 subfamily. Truncated C-terminus. Truncated C-terminus. Truncated C-terminus.