HDAC11 (Histone Deacetylase 11) is the sole member of the Class IV histone deacetylases, representing the smallest and most recently characterized HDAC enzyme. It catalyzes the removal of acetyl groups from lysine residues on histones and non-histone proteins, regulating gene expression, immune responses, and cellular metabolism. In the brain, HDAC11 may regulate neuronal gene expression and immune responses in glial cells. [@gaofeng2016]
HDAC11 (Histone Deacetylase 11) is the sole member of the Class IV histone deacetylases, representing the smallest and most recently characterized HDAC enzyme. It catalyzes the removal of acetyl groups from lysine residues on histones and non-histone proteins, regulating gene expression, immune responses, and cellular metabolism. In the brain, HDAC11 may regulate neuronal gene expression and immune responses in glial cells. [@gaofeng2016]
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Histone Deacetylase 11 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Histone Deacetylase 11 (HDAC11)</td></tr>
<tr><td><strong>Gene</strong></td><td>[HDAC11](/genes/hdac11)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9P0K5](https://www.uniprot.org/uniprot/Q9P0K5)</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>4RUI, 5ICR</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>39 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Class IV Histone Deacetylase</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/huntington" style="color:#ef9a9a">Huntington</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/neurodegeneration" style="color:#ef9a9a">Neurodegeneration</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">58 edges</a></td>
</tr>
</table>
</div>
HDAC11 is a 347 amino acid protein containing a catalytic domain distinct from Class I, II, and III enzymes. The structure reveals a Rossmann-fold-like catalytic core with a unique zinc-binding motif. HDAC11 is the smallest [HDAC](/entities/hdac-enzymes) with unique structural features.
| Feature | Function |
|---------|----------|
| Rossmann-fold catalytic core | Central deacetylase activity |
| Zinc-binding motif | Required for catalytic function |
| N-terminal regulatory region | Protein-protein interactions |
| L1 and L2 loops | Substrate specificity |
HDAC11 catalyzes the removal of acetyl groups from lysine residues on histones, primarily H3 and H4 tails. This modifies chromatin structure and regulates gene transcription. [@grunstein1997]
Histone acetylation dynamics:
HDAC11 also deacetylates non-histone proteins, including:
In immune cells, HDAC11 regulates: [@park2016]
In the central nervous system:
| Cancer Type | HDAC11 Role | Evidence |
|-------------|-------------|----------|
| Breast cancer | Overexpression promotes growth | High HDAC11 correlates with poor prognosis |
| Prostate cancer | Androgen receptor regulation | Tumor-specific expression |
| Colorectal cancer | Cell cycle progression | Knockdown reduces proliferation |
| Glioma | Stem cell maintenance | Expressed in glioma stem cells |
HDAC11 is frequently overexpressed in various cancers and promotes tumor growth through epigenetic and non-epigenetic mechanisms. [@khan2018]
While HDAC11 is the least studied HDAC in neurodegeneration, emerging evidence suggests important roles:
Alzheimer's Disease:
The balance of histone acetylation/deacetylation is critical for neuronal health: [@shen2015]
| Compound | Selectivity | Stage | Application |
|----------|-------------|-------|-------------|
| HDAC11-IN-1 | HDAC11-specific | Preclinical | Tool compound |
| HDAC11-IN-2 | HDAC11-selective | Discovery | Lead optimization |
| JH-X-01-02 | HDAC11>others | Preclinical | Cancer |
Pan-HDAC inhibitors that target HDAC11:
| HDAC Class | Members | Subcellular Location | Function |
|------------|---------|---------------------|----------|
| Class I | HDAC1,2,3,8 | Nucleus | Corepressor complexes |
| Class IIa | HDAC4,5,7,9 | Nucleus/Cytoplasm | Signal-dependent |
| Class IIb | HDAC6,10 | Cytoplasm | Cytoplasmic proteins |
| Class III | SIRT1-7 | Multiple | NAD+-dependent |
| Class IV | HDAC11 | Nucleus/Cytoplasm | Unique substrates |