HDAC3
GeneName
HDAC3
Summary
HDAC3, also known as histone deacetylase 3 or HD-3, is a 49 kDa enzyme that plays a pivotal role in the regulation of gene expression through its histone deacetylase activity. It is primarily localised in the nucleus but can also be found in the cytoplasm and other cellular compartments such as the Golgi apparatus and plasma membrane. HDAC3 is involved in chromatin organisation and transcriptional repression, interacting with various transcription factors and complexes to modulate gene expression. Its functions extend to DNA repair, response to mechanical stimuli, and regulation of apoptotic processes, highlighting its significance in cellular homeostasis and development.
Importance
HDAC3 is relevant to: - Epigenetic regulation of gene expression, influencing cell differentiation and development. - The response to various stimuli, including mechanical and hormonal signals, which is crucial for maintaining cellular function. - Cancer research, as it is often implicated in tumourigenesis through its role in regulating transcription and cell cycle progression. - Neurobiology, due to its involvement in neural precursor cell proliferation and apoptosis, which has implications for neurodegenerative diseases.
Top Products
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Abcam Product Citation Summary
The data indicates that HDAC3 is being studied in various human contexts, particularly in relation to HIV-1 reactivation, hepatocellular carcinoma (HCC), and glioma. The consistent use of Western blotting suggests a focus on protein expression levels in these conditions.
Abcam Product Citation Table
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 (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892, PubMed:22230954). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity (PubMed:23911289, PubMed:22230954). 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 (PubMed:23911289). 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 (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). 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 (By similarity). 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 a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl), 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) and isonicotinyl acyl groups from lysine residues, leading to protein decrotonylation, delactylation, de-2-hydroxyisobutyrylation and deisonicotinylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293, PubMed:34545082, PubMed:35044827). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290).
Post-translational modifications
Sumoylated in vitro.
Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation.
Sequence Similarities
Belongs to the histone deacetylase family. HD type 1 subfamily.
Tissue Specificity
Widely expressed.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Cytoplasm
- Cytosol
- Colocalizes with XBP1 and AKT1 in the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus in the presence of CCAR2 (PubMed:21030595).
Alternative names
Histone deacetylase 3, HD3, Protein deacetylase HDAC3, Protein deacylase HDAC3, RPD3-2, SMAP45, HDAC3
Database links
swissprot:O15379 omim:605166 omim:600848 swissprot:Q9Y618 entrezGene:8841 entrezGene:9612