HDAC4

Histone deacetylase 4 ;
HD4 ;

catalytic activity:Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.,domain:The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.,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.,PTM:Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues is required for the interaction with 14-3-3.,PTM:Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.,similarity:Belongs to the histone deacetylase family. Type 2 subfamily.,subcellular location: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-246, Ser-467 and Ser-632 by CaMK4. The nuclear localization probably depends on sumoylation.,subunit:Interacts with HDAC7 (By similarity). Homodimer. Homodimerization via its N-terminal domain. Interacts with MEF2C, AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with BTBD14B (By similarity). Interacts with KDM5B.,tissue specificity:Ubiquitous.,

negative regulation of transcription from RNA polymerase II promoter, skeletal system development, cell activation,immune system development, leukocyte differentiation, muscle system process, regulation of carbohydrate metabolic process, regulation of glycolysis, chromatin organization, chromatin remodeling, transcription, regulation of transcription, DNA-dependent, regulation of transcription from RNA polymerase II promoter, protein amino acid deacetylation, defense response, inflammatory response, positive regulation of cell proliferation, negative regulation of cell proliferation, response to wounding, negative regulation of biosynthetic process, positive regulation of biosynthetic process, regulation of catabolic process, negative regulation of catabolic process, response to organic substance, regulation of specific transcription from RNA polymerase II promoter, positive regulation of specific transcription from RNA polymerase II promoter, negative regulation of specific transcription from RNA polymerase II promoter, positive regulation of macromolecule biosynthetic process, negative regulation of macromolecule biosynthetic process, positive regulation of macromolecule metabolic process, negative regulation of macromolecule metabolic process, positive regulation of gene expression, negative regulation of gene expression, regulation of cellular carbohydrate metabolic process, negative regulation of cellular carbohydrate metabolic process, regulation of myotube differentiation, negative regulation of myotube differentiation, regulation of glucose metabolic process,response to inactivity, response to muscle inactivity, response to stimulus involved in regulation of muscle adaptation,response to muscle inactivity involved in regulation of muscle adaptation, cardiac muscle adaptation, striated muscle adaptation, response to denervation involved in regulation of muscle adaptation, muscle hypertrophy, striated muscle hypertrophy, cardiac muscle hypertrophy, regulation of striated muscle tissue development, negative regulation of transcription, chromatin modification, covalent chromatin modification, histone modification, histone deacetylation,peptidyl-lysine modification, hemopoiesis, lymphocyte differentiation, B cell differentiation, negative regulation of cellular biosynthetic process, positive regulation of cellular biosynthetic process, regulation of cellular catabolic process, negative regulation of cellular catabolic process, regulation of protein modification process, positive regulation of protein modification process, regulation of cellular protein metabolic process, positive regulation of cellular protein metabolic process, negative regulation of gene-specific transcription, regulation of gene-specific transcription, regulation of protein sumoylation, positive regulation of protein sumoylation, response to cytokine stimulus, peptidyl-lysine deacetylation, B cell activation, regulation of cell proliferation, response to drug, positive regulation of gene-specific transcription, positive regulation of DNA binding, negative regulation of DNA binding,regulation of protein binding, negative regulation of transcription factor activity, regulation of generation of precursor metabolites and energy, regulation of carbohydrate catabolic process, regulation of cellular carbohydrate catabolic process, muscle adaptation, regulation of muscle adaptation, regulation of system process, negative regulation of molecular function, positive regulation of molecular function, leukocyte activation, regulation of transcription, negative regulation of cell differentiation, negative regulation of glycolysis, negative regulation of transcription, DNA-dependent,positive regulation of transcription, DNA-dependent, negative regulation of carbohydrate metabolic process, negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process, positive regulation of transcription, positive regulation of transcription from RNA polymerase II promoter, lymphocyte activation, hemopoietic or lymphoid organ development,regulation of muscle development, regulation of skeletal muscle tissue development, regulation of skeletal muscle fiber development, regulation of transcription factor activity, positive regulation of transcription factor activity,regulation of binding, positive regulation of binding, negative regulation of binding, regulation of DNA binding,regulation of muscle cell differentiation, negative regulation of muscle cell differentiation, regulation of striated muscle cell differentiation, negative regulation of striated muscle cell differentiation, negative regulation of nitrogen compound metabolic process, positive regulation of nitrogen compound metabolic process, positive regulation of protein metabolic process, regulation of RNA metabolic process, negative regulation of RNA metabolic process, positive regulation of RNA metabolic process, chromosome organization, regulation of cell development, response to interleukin-1,

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-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation. Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (By similarity). .

Ubiquitous.