IL1RL1 Protein (ST2)

IL1RL1 Protein - Interleukin-1 Receptor-Like 1 (ST2)

Introduction

Il1Rl1 Protein (St2) 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"> [@griesenauer2017]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Interleukin-1 Receptor-Like 1 (ST2)</td></tr>
<tr><td><strong>Gene</strong></td><td>IL1RL1</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9INT6</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>4E90, 4R0U</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~63 kDa (membrane form)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cell membrane</td></tr>
<tr><td><strong>Protein Family</strong></td><td>IL-1 Receptor Family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>
</div>

Overview

ST2 (Interleukin-1 Receptor-Like 1, encoded by IL1RL1) is a member of the IL-1 receptor family and serves as the receptor for IL-33. ST2 exists in both membrane-bound (ST2L) and soluble (sST2) forms. The IL-33/ST2 axis plays critical roles in type 2 immune responses, tissue repair, and has been implicated in inflammatory and neurodegenerative diseases.

Structure

ST2 is a member of the IL-1 receptor family:

...

IL1RL1 Protein - Interleukin-1 Receptor-Like 1 (ST2)

Introduction

Il1Rl1 Protein (St2) 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"> [@griesenauer2017]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">Protein Information</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Interleukin-1 Receptor-Like 1 (ST2)</td></tr>
<tr><td><strong>Gene</strong></td><td>IL1RL1</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>Q9INT6</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>4E90, 4R0U</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~63 kDa (membrane form)</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cell membrane</td></tr>
<tr><td><strong>Protein Family</strong></td><td>IL-1 Receptor Family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>
</div>

Overview

ST2 (Interleukin-1 Receptor-Like 1, encoded by IL1RL1) is a member of the IL-1 receptor family and serves as the receptor for IL-33. ST2 exists in both membrane-bound (ST2L) and soluble (sST2) forms. The IL-33/ST2 axis plays critical roles in type 2 immune responses, tissue repair, and has been implicated in inflammatory and neurodegenerative diseases.

Structure

ST2 is a member of the IL-1 receptor family:

Domain Architecture

• Signal peptide: N-terminal signal peptide
• Immunoglobulin-like domain: Three Ig-like domains for ligand binding
• Transmembrane domain: Single pass transmembrane helix
• TIR domain: Toll/IL-1 receptor signaling domain

Isoforms

• ST2L: Membrane-bound functional receptor
• sST2: Soluble form acts as decoy receptor

Normal Function

ST2 is the receptor for IL-33:

Signaling Pathways

MyD88-dependent pathway: [NF-kB](/entities/nf-kb) and MAPK activation

IL-33 binding: Triggers pro-inflammatory responses

Soluble ST2: Neutralizes IL-33, regulates signaling

Cellular Functions

• IL-33 receptor: Binds IL-33 with high affinity
• Type 2 immunity: Promotes Th2 responses
• Tissue repair: Involved in tissue homeostasis

Role in Disease

Alzheimer Disease

• ST2 expression altered in AD brain
• Modulates IL-33 signaling in neuroinflammation
• ST2+ cells in AD brain regions
• Potential therapeutic target

Parkinson Disease

• ST2 in PD pathogenesis
• Role in neuroinflammation
• Dopaminergic neuron survival

Asthma

• ST2 critical in asthma pathogenesis
• IL-33/ST2 axis drives Th2 inflammation
• Therapeutic targeting in clinical trials

Cardiovascular Disease

• sST2 as biomarker for cardiac stress
• Prognostic value in heart failure

Expression

| Cell Type | Expression Level | Notes |
|----------|-----------------|-------|
| T Cells | High | Especially Th2 cells |
| Mast Cells | High | Allergic response |
| Eosinophils | Moderate | Type 2 inflammation |
| [Astrocytes](/entities/astrocytes) | Moderate | Brain expression |
| [Microglia](/entities/microglia) | Low-Moderate | Immune cells |
| Cardiac Cells | High | Cardiomyocytes |

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 |
| ST2 Blocking | Antibodies | Clinical trials | Various diseases |

Protein Interactions

• IL-33: Primary ligand
• MyD88: Primary adaptor protein
• IL-1RAcP: Co-receptor
• TIRAP: Adaptor protein

Background

The study of Il1Rl1 Protein (St2) 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

• IL1RL1 Gene
• [IL33](/genes/il33)
• Interleukins
• IL-1 Receptor Family
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)
• [Cytokines](/mechanisms/neuroinflammation)

External Links

• [UniProt: IL1RL1](https://www.uniprot.org/uniprot/Q9INT6)
• [PDB: ST2](https://www.ebi.ac.uk/pdbe/pdbe-search?targetUrl=http://www.ebi.ac.uk/pdbe/entry/pdb/4e90)
• [NCBI Protein: IL1RL1](https://www.ncbi.nlm.nih.gov/protein/9173)

References

Schmitz J, Owyang A, Oldham E, et al, IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines (2005)

Griesenauer B, Paczesny S, The ST2/IL-33 axis in immune cells during inflammatory diseases (2017)