Protein: Histone deacetylase 5 (HD5) (EC 3.5.1.98) (Antigen NY-CO-9) (Q9UQL6)
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 by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Serves as a corepressor of RARA and causes its deacetylation. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response.
Subcellular location: Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-259 and Ser-498 by AMPK, CaMK1 and SIK1.
Sequence: MNSPNESDGMSGREPSLEILPRTSLHSIPVTVEVKPVLPRAMPSSMGGGGGGSPSPVELRGALVGSVDPTLREQQLQQELLALKQQQQLQKQLLFAEFQKQHDHLTRQHEVQLQKHLKQQQEMLAAKQQQEMLAAKRQQELEQQRQREQQRQEELEKQRLEQQLLILRNKEKSKESAIASTEVKLRLQEFLLSKSKEPTPGGLNHSLPQHPKCWGAHHASLDQSSPPQSGPPGTPPSYKLPLPGPYDSRDDFPLRKTASEPNLKVRSRLKQKVAERRSSPLLRRKDGTVISTFKKRAVEITGAGPGASSVCNSAPGSGPSSPNSSHSTIAENGFTGSVPNIPTEMLPQHRALPLDSSPNQFSLYTSPSLPNISLGLQATVTVTNSHLTASPKLSTQQEAERQALQSLRQGGTLTGKFMSTSSIPGCLLGVALEGDGSPHGHASLLQHVLLLEQARQQSTLIAVPLHGQSPLVTGERVATSMRTVGKLPRHRPLSRTQSSPLPQSPQALQQLVMQQQHQQFLEKQKQQQLQLGKILTKTGELPRQPTTHPEETEEELTEQQEVLLGEGALTMPREGSTESESTQEDLEEEDEEDDGEEEEDCIQVKDEEGESGAEEGPDLEEPGAGYKKLFSDAQPLQPLQVYQAPLSLATVPHQALGRTQSSPAAPGGMKSPPDQPVKHLFTTGVVYDTFMLKHQCMCGNTHVHPEHAGRIQSIWSRLQETGLLSKCERIRGRKATLDEIQTVHSEYHTLLYGTSPLNRQKLDSKKLLGPISQKMYAVLPCGGIGVDSDTVWNEMHSSSAVRMAVGCLLELAFKVAAGELKNGFAIIRPPGHHAEESTAMGFCFFNSVAITAKLLQQKLNVGKVLIVDWDIHHGNGTQQAFYNDPSVLYISLHRYDNGNFFPGSGAPEEVGGGPGVGYNVNVAWTGGVDPPIGDVEYLTAFRTVVMPIAHEFSPDVVLVSAGFDAVEGHLSPLGGYSVTARCFGHLTRQLMTLAGGRVVLALEGGHDLTAICDASEACVSALLSVELQPLDEAVLQQKPNINAVATLEKVIEIQSKHWSCVQKFAAGLGRSLREAQAGETEEAETVSAMALLSVGAEQAQAAAAREHSPRPAEEPMEQEPAL
InterPro domains: - IPR037138: Histone deacetylase domain superfamily (homologous_superfamily) [680-1066]
- IPR023696: Ureohydrolase domain superfamily (homologous_superfamily) [682-1062]
- IPR046949: Histone deacetylase 4/5/7/9 (family) [25-1122]
- IPR024643: Histone deacetylase, glutamine rich N-terminal domain (domain) [67-164]
- IPR023801: Histone deacetylase domain (domain) [704-1022]
- IPR000286: Histone deacetylase HDAC (family) [829-964]
Interaction partners: - Nuclear receptor corepressor 1
- Histone deacetylase 4
- Nuclear receptor subfamily 2 group E member 1
- Nuclear receptor corepressor 2
- Calcium/calmodulin-dependent protein kinase type IV
- Histone deacetylase 3
- Myocyte-specific enhancer factor 2D
- Myocyte-specific enhancer factor 2A
- Myocyte-specific enhancer factor 2C
- Serine/threonine-protein kinase D1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0008134 (transcription factor binding), GO:0019899 (enzyme binding), GO:0016810 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds), GO:0033558 (protein lysine deacetylase activity), GO:0019213 (deacetylase activity), GO:0004407 (histone deacetylase activity), GO:0140297 (DNA-binding transcription factor binding), GO:0016811 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0002376 (immune system process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0001775 (cell activation), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0045321 (leukocyte activation), GO:0019222 (regulation of metabolic process), GO:0051241 (negative regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0009892 (negative regulation of metabolic process), GO:0050793 (regulation of developmental process), GO:0033555 (multicellular organismal response to stress), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0001503 (ossification), GO:0006950 (response to stress), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0048729 (tissue morphogenesis), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0034405 (response to fluid shear stress), GO:0001649 (osteoblast differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0006952 (defense response), GO:0060255 (regulation of macromolecule metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0031324 (negative regulation of cellular metabolic process), GO:0010033 (response to organic substance), GO:0046649 (lymphocyte activation), GO:1901862 (negative regulation of muscle tissue development), GO:0035295 (tube development), GO:0048635 (negative regulation of muscle organ development), GO:0042127 (regulation of cell population proliferation), GO:0009888 (tissue development), GO:1901698 (response to nitrogen compound), GO:0045596 (negative regulation of cell differentiation), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0033554 (cellular response to stress), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0045595 (regulation of cell differentiation), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0016043 (cellular component organization), GO:0080090 (regulation of primary metabolic process), GO:0048634 (regulation of muscle organ development), GO:1901861 (regulation of muscle tissue development), GO:0008284 (positive regulation of cell population proliferation), GO:1902074 (response to salt), GO:0035239 (tube morphogenesis), GO:0072001 (renal system development), GO:0030097 (hemopoiesis), GO:2001014 (regulation of skeletal muscle cell differentiation), GO:0060562 (epithelial tube morphogenesis), GO:0002521 (leukocyte differentiation), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0016202 (regulation of striated muscle tissue development), GO:0060284 (regulation of cell development), GO:2000179 (positive regulation of neural precursor cell proliferation), GO:0006325 (chromatin organization), GO:0002009 (morphogenesis of an epithelium), GO:0051147 (regulation of muscle cell differentiation), GO:0010468 (regulation of gene expression), GO:0030098 (lymphocyte differentiation), GO:2000177 (regulation of neural precursor cell proliferation), GO:0045668 (negative regulation of osteoblast differentiation), GO:0042220 (response to cocaine), GO:0006954 (inflammatory response), GO:0007399 (nervous system development), GO:0061326 (renal tubule development), GO:0010243 (response to organonitrogen compound), GO:0072359 (circulatory system development), GO:0031326 (regulation of cellular biosynthetic process), GO:0072091 (regulation of stem cell proliferation), GO:0007507 (heart development), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:2000648 (positive regulation of stem cell proliferation), GO:0071498 (cellular response to fluid shear stress), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0014070 (response to organic cyclic compound), GO:0051252 (regulation of RNA metabolic process), GO:0060429 (epithelium development), GO:0045667 (regulation of osteoblast differentiation), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010629 (negative regulation of gene expression), GO:0002076 (osteoblast development), GO:0042113 (B cell activation), GO:0043279 (response to alkaloid), GO:2001141 (regulation of RNA biosynthetic process), GO:0051153 (regulation of striated muscle cell differentiation), GO:0006355 (regulation of DNA-templated transcription), GO:0061333 (renal tubule morphogenesis), GO:1903131 (mononuclear cell differentiation), GO:0030183 (B cell differentiation), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0010830 (regulation of myotube differentiation), 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)