Hdac4
Domain
The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.
Function
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. Deacetylates HSPA1A and HSPA1A at 'Lys-77' leading to their preferential binding to co-chaperone STUB1.
Post-translational modifications
Phosphorylated by CaMK4 at Ser-245, Ser-465 and Ser-629. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 (By similarity).
Sumoylation on Lys-556 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.
Sequence Similarities
Belongs to the histone deacetylase family. HD type 2 subfamily.
Cellular localization
- Nucleus
- Cytoplasm
- Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-245, Ser-465 and Ser-629 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation (By similarity). Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (PubMed:22318228).
Alternative names
Histone deacetylase 4, HD4, Hdac4