Protein: Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-) (Q6P6W3)
Organism: Rattus norvegicus (Rat)
Function: Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. 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. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (By similarity). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (By similarity). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner. During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1. The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA. Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response. In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (By similarity). Catalyzes decrotonylation of MAPRE1/EB1 (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:O15379}. Chromosome {ECO:0000250|UniProtKB:O15379}. Cytoplasm {ECO:0000250|UniProtKB:O15379}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:O15379}. Note=Colocalizes with XBP1 and AKT1 in the cytoplasm. Predominantly expressed in the nucleus in the presence of CCAR2. {ECO:0000250|UniProtKB:O15379}.
InterPro domains:
- IPR037138: Histone deacetylase domain superfamily (homologous_superfamily) [1-376]
- IPR000286: Histone deacetylase HDAC (family) [131-259]
- IPR023696: Ureohydrolase domain superfamily (homologous_superfamily) [4-369]
- IPR003084: Class I/II Histone deacetylase HDAC (family) [1-427]
- IPR023801: Histone deacetylase domain (domain) [22-312]
Sequence:
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCRFHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVISQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDNDKESDVEI
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0003682 (chromatin binding), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:1990841 (promoter-specific chromatin binding), GO:0031072 (heat shock protein binding), GO:0019213 (deacetylase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0042221 (response to chemical), GO:0051716 (cellular response to stimulus), GO:0071840 (cellular component organization or biogenesis), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0016358 (dendrite development), GO:0070887 (cellular response to chemical stimulus), GO:0048731 (system development), GO:0016043 (cellular component organization), GO:0060996 (dendritic spine development), GO:0010033 (response to organic substance), GO:0022008 (neurogenesis), GO:0030030 (cell projection organization), GO:0007399 (nervous system development), GO:0071310 (cellular response to organic substance), GO:0014070 (response to organic cyclic compound), GO:0030182 (neuron differentiation), GO:0048666 (neuron development), GO:0031175 (neuron projection development), GO:0048699 (generation of neurons), GO:0120036 (plasma membrane bounded cell projection organization), GO:0071407 (cellular response to organic cyclic compound)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)