Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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.

Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256)

Homodimer. Homodimerization via its N-terminal domain (PubMed:12032081). Interacts with MEF2A (PubMed:10487761).

Interacts with MEF2C and MEF2D (PubMed:10523670). Interacts with AHRR (By similarity). Interacts with NR2C1 (PubMed:11463856).

Interacts with HDAC7 (By similarity). Interacts with a 14-3-3 chaperone proteins in a phosphorylation dependent manner (PubMed:10958686). Interacts with 14-3-3 protein YWHAB (PubMed:33537682).

Interacts with BTBD14B (By similarity). Interacts with KDM5B (PubMed:17373667). Interacts with MYOCD (By similarity).

Interacts with MORC2 (PubMed:20110259). Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2 (PubMed:25752541).

Interacts with EP300 in the presence of TFAP2C (PubMed:24413532). Interacts with HSPA1A and HSPA1B leading to their deacetylation at 'Lys-77' (PubMed:27708256). Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (By similarity).

Interacts with DHX36 (By similarity). Interacts with SIK3; this interaction leads to HDAC4 retention in the cytoplasm (By similarity). Interacts with ZNF638 (PubMed:30487602)

Ubiquitous

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm

The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2

• Unknown disease
• Neurodevelopmental disorder with central hypotonia and dysmorphic facies (NEDCHF)

  An autosomal dominant disease characterized by global developmental delay, impaired intellectual development, seizures, distinctive facial features, scoliosis, delayed closure of the anterior fontanel, and non-specific brain abnormalities.