Protein: Histone deacetylase 4 (HD4) (EC 3.5.1.98) (P56524)
Organism: Homo sapiens (Human)
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. 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.
Subcellular location: Nucleus. Cytoplasm. Note=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). {ECO:0000250|UniProtKB:Q6NZM9}.
Sequence: MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLPVAEPALREQQLQQELLALKQKQQIQRQILIAEFQRQHEQLSRQHEAQLHEHIKQQQEMLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVLNKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPATGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLLEQPPAQAPLVTGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQNAQALQHLVIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPYLDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRFTTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNANAVRSMEKVMEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEEEPPL
InterPro domains: - IPR037138: Histone deacetylase domain superfamily (homologous_superfamily) [651-1036]
- IPR023696: Ureohydrolase domain superfamily (homologous_superfamily) [651-1032]
- IPR046949: Histone deacetylase 4/5/7/9 (family) [25-1084]
- IPR024643: Histone deacetylase, glutamine rich N-terminal domain (domain) [62-152]
- IPR023801: Histone deacetylase domain (domain) [675-992]
- IPR000286: Histone deacetylase HDAC (family) [799-934]
Interaction partners: - Nuclear receptor corepressor 2
- Nuclear receptor corepressor 1
- Runt-related transcription factor 2
- Ankyrin repeat family A protein 2
- 14-3-3 protein gamma
- Myocyte-specific enhancer factor 2C
- Heat shock protein HSP 90-alpha
- Myocyte-specific enhancer factor 2A
- Histone deacetylase 5
- B-cell lymphoma 6 protein
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0044877 (protein-containing complex binding), GO:0003682 (chromatin binding), GO:0097159 (organic cyclic compound binding), GO:0003712 (transcription coregulator activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0008134 (transcription factor binding), GO:0003676 (nucleic acid binding), GO:0031491 (nucleosome binding), GO:0016810 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds), GO:0003714 (transcription corepressor activity), GO:0019899 (enzyme binding), GO:0033558 (protein lysine deacetylase activity), GO:0019213 (deacetylase activity), GO:0004407 (histone deacetylase activity), GO:0140297 (DNA-binding transcription factor binding), GO:0003677 (DNA binding), GO:0019900 (kinase binding), GO:0019901 (protein kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0048519 (negative regulation of biological process), GO:0032501 (multicellular organismal process), GO:0050793 (regulation of developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0051241 (negative regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0006950 (response to stress), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0009892 (negative regulation of metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:2000026 (regulation of multicellular organismal development), GO:0044085 (cellular component biogenesis), GO:0045596 (negative regulation of cell differentiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0048731 (system development), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0006952 (defense response), GO:0060255 (regulation of macromolecule metabolic process), GO:0045595 (regulation of cell differentiation), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:1901343 (negative regulation of vasculature development), GO:0072001 (renal system development), GO:0006954 (inflammatory response), GO:0010556 (regulation of macromolecule biosynthetic process), GO:1901342 (regulation of vasculature development), GO:0031326 (regulation of cellular biosynthetic process), GO:0006325 (chromatin organization), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0051253 (negative regulation of RNA metabolic process), GO:0034330 (cell junction organization), GO:0001822 (kidney development), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:0007416 (synapse assembly), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0034329 (cell junction assembly), GO:0006357 (regulation of transcription by RNA polymerase II), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0045892 (negative regulation of DNA-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)