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. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. 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 (By similarity). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). 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. 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. 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 (By similarity). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA. Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response. 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 (By similarity). 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 BTBD14B (PubMed:16033423). Interacts with HDAC7 and HDAC9. Interacts with HDAC10, DAXX and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Component of the Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with and deacetylates MAPK14. Interacts with ZMYND15. Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements. Interacts with INSM1. Interacts with XBP1; the interaction occurs in endothelial cell (EC) under disturbed flow. Interacts (via C-terminus) with CCAR2 (via N-terminus). Interacts with and deacetylates MEF2D (By similarity). Interacts with BEND3 (By similarity). Interacts with NKAPL (By similarity). 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 (By similarity). Interacts with FBXL3 and ARNTL/BMAL1 (By similarity). Interacts with NCOR1 (By similarity). Interacts with RARA (By similarity). Interacts with SETD5 (By similarity). Colocalizes with XBP1 and AKT1 in the cytoplasm. Predominantly expressed in the nucleus in the presence of CCAR2 (By similarity). Belongs to the histone deacetylase family. HD type 1 subfamily.