IL33 Protein

IL33 Protein - Interleukin-33

Introduction

Il33 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox .infobox-protein"> [@xiong2014]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Interleukin-33 (IL-33)</td></tr>
<tr><td><strong>Gene</strong></td><td>IL33</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9BY84</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>4KMC, 5V4D</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~30 kDa (full-length)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm, Secreted</td></tr>
<tr><td><strong>Protein Family</strong></td><td>IL-1 Family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/depression" style="color:#ef9a9a">Depression</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">25 edges</a></td>
</tr>
</table>
</div>

Overview

...

IL33 Protein - Interleukin-33

Introduction

Il33 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox .infobox-protein"> [@xiong2014]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Interleukin-33 (IL-33)</td></tr>
<tr><td><strong>Gene</strong></td><td>IL33</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9BY84</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>4KMC, 5V4D</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~30 kDa (full-length)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Nucleus, Cytoplasm, Secreted</td></tr>
<tr><td><strong>Protein Family</strong></td><td>IL-1 Family</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/depression" style="color:#ef9a9a">Depression</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">25 edges</a></td>
</tr>
</table>
</div>

Overview

IL-33 (Interleukin-33) is a cytokine belonging to the IL-1 family that functions as an alarmin released upon cell damage. IL-33 signals through the ST2 receptor (IL1RL1) and promotes type 2 immune responses. It is expressed in various tissues including the brain, where it plays important roles in neuroinflammation and has been implicated in neurodegenerative diseases.

Structure

IL-33 is a cytokine with dual function:

Domain Architecture

• N-terminal domain: Contains chromatin-binding motif
• Hematopoietic nuclear domain: Nuclear localization
• IL-1-like domain: Receptor-binding region at C-terminus
• Protease cleavage sites: Generates active fragments

Structure-Function

• Full-length IL-33 is biologically active
• Acts as both nuclear cytokine and extracellular alarmin
• Proteolytic processing enhances activity

Normal Function

IL-33 has dual functions as nuclear cytokine and alarmin:

Cellular Functions

• Nuclear cytokine: May regulate gene transcription
• Alarmin release: Released from damaged cells
• Type 2 immunity: Promotes Th2 responses

Signaling Pathways

ST2/IL-1RAcP receptor: MyD88-dependent signaling

[NF-kB](/entities/nf-kb) activation: Pro-inflammatory responses

MAPK pathways: Cell survival and activation

Biological Activities

• Th2 cytokine production: IL-4, IL-5, IL-13
• Mast cell activation: Histamine, cytokines
• Eosinophil recruitment: Inflammatory responses

Role in Disease

Alzheimer Disease

• IL-33 expression altered in AD brain
• Modulates microglial activation and neuroinflammation
• IL-33+ cells near amyloid plaques

Parkinson Disease

• IL-33 in PD pathogenesis
• Neuroinflammation and dopaminergic neuron survival
• May have protective or pathogenic effects

Multiple Sclerosis

• IL-33 polymorphisms linked to MS risk
• Role in demyelination and neuroinflammation

Expression

| Cell Type | Expression Level | Notes |
|----------|-----------------|-------|
| [Astrocytes](/entities/astrocytes) | High | Brain expression |
| [Neurons](/entities/neurons) | Moderate | Some neuronal types |
| [Microglia](/entities/microglia) | Moderate | Immune cells |
| Endothelial Cells | High | Vascular cells |
| Fibroblasts | High | Stromal cells |
| Epithelial Cells | Moderate | Barrier tissues |

Therapeutic Targeting

| Approach | Agent | Status | Notes |
|----------|-------|--------|-------|
| ST2 Antagonists | Soluble ST2-Fc | Research | Block IL-33 binding |
| Anti-IL-33 | Monoclonal antibodies | Research | Neutralize IL-33 |
| Natural Compounds | Various | Preclinical | Modulate pathway |

Protein Interactions

• ST2 (IL1RL1): Primary receptor
• IL-1RAcP: Co-receptor for signaling
• Soluble ST2: Decoy receptor
• Chromatin: Nuclear binding

Background

The study of Il33 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• IL33 Gene
• [IL1RL1](/genes/il1rl1)
• Interleukins
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)
• [Cytokines](/mechanisms/neuroinflammation)

External Links

• [UniProt: IL33](https://www.uniprot.org/uniprot/Q9BY84)
• [PDB: IL33](https://www.ebi.ac.uk/pdbe/pdbe-search?targetUrl=http://www.ebi.ac.uk/pdbe/entry/pdb/4kmc)
• [NCBI Protein: IL33](https://www.ncbi.nlm.nih.gov/protein/90865)

References

Liew FY, Girard JP, Turnquist HR, Interleukin-33 in health and disease (2016)

Xiong Z, Thangavel R, Kempuraj D, et al, Alzheimer disease: evidence for the altered expression of IL-33 and its receptor ST2 (2014)