Annexin A11 Protein

Annexin A11 — Calcium-Dependent Phospholipid Binding Protein

Introduction

Annexin A11 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.

Overview

This page provides comprehensive information about Annexin A11 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases. [@toth2021]

<div class="infobox infobox-protein"> [@gao2020]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Annexin A11</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Annexin A11</td></tr>
<tr><td><strong>Gene</strong></td><td>[ANXA11](/genes/anxa11)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P50991](https://www.uniprot.org/uniprot/P50991)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>5YUE, 6B8J</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>54 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, plasma membrane, nuclear envelope</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Annexin family</td></tr>
</table>
</div>

Structure

...

Annexin A11 — Calcium-Dependent Phospholipid Binding Protein

Introduction

Annexin A11 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.

Overview

This page provides comprehensive information about Annexin A11 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases. [@toth2021]

<div class="infobox infobox-protein"> [@gao2020]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Annexin A11</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Annexin A11</td></tr>
<tr><td><strong>Gene</strong></td><td>[ANXA11](/genes/anxa11)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P50991](https://www.uniprot.org/uniprot/P50991)</td></tr>
<tr><td><strong>PDB ID</strong></td><td>5YUE, 6B8J</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>54 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Cytoplasm, plasma membrane, nuclear envelope</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Annexin family</td></tr>
</table>
</div>

Structure

Annexin A11 is a member of the annexin family of calcium-dependent phospholipid-binding proteins. The protein consists of four annexin repeats, each comprising a conserved core domain that binds calcium and phospholipids. ANXA11 also contains an N-terminal domain with a prion-like domain that mediates protein-protein interactions.

Normal Function

Annexin A11 participates in various cellular processes:

• Membrane organization: Binds to phospholipid membranes in a calcium-dependent manner
• Vesicle trafficking: Regulates exocytosis and endocytosis
• [Autophagy](/entities/autophagy): Involved in autophagosome formation and lysosomal function
• [TDP-43](/proteins/tdp-43) binding: Interacts with [TDP-43](/mechanisms/tdp-43-proteinopathy) and influences its localization

Role in Disease

Amyotrophic Lateral SALS (ALS)

ANXA11 mutations cause autosomal dominant ALS:

• Calcium dysregulation: Impaired calcium binding affects neuronal function
• TDP-43 mislocalization: Disrupted interaction with TDP-43 leads to nuclear loss
• Autophagy defects: Impaired lysosomal function and protein clearance

Progressive Supranuclear Palsy (PSP)

ANXA11 variants are risk factors for PSP:

• [Tau](/proteins/tau) pathology: Potential involvement in [tau](/proteins/tau) aggregation or clearance
• Brainstem vulnerability: Selective susceptibility of brainstem [neurons](/entities/neurons)

| Variant | Disease | Mechanism |
|---------|---------|-----------|
| G38R | ALS | Disrupted calcium binding |
| A71T | ALS | Impaired autophagy |
| D40G | ALS | TDP-43 mislocalization |
| R235Q | ALS | Aggregate formation |

Therapeutic Targeting

• Gene therapy: AAV-mediated ANXA11 delivery
• Calcium modulators: Target calcium signaling pathways
• Autophagy enhancers: Boost lysosomal function

Key Publications

[28191688](https://pubmed.ncbi.nlm.nih.gov/28191688/): ANXA11 mutations in ALS. Nat. Neurosci, 2017.

[30655511](https://pubmed.ncbi.nlm.nih.gov/30655511/): Annexin A11 in TDP-43 proteinopathy. Acta Neuropathol, 2018.

[32877956](https://pubmed.ncbi.nlm.nih.gov/32877956/): ANXA11 and autophagy in neurodegeneration. Autophagy, 2020.

See Also

• [ANXA11 Gene](/proteins/anxa11-protein)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Progressive Supranuclear Palsy](/diseases/psp)
• [TDP-43 Proteinopathy](/mechanisms/rna-metabolism-dysregulation)
• [Motor Neurons](/cell-types/spinal-motor-neurons)

Clinical Significance

Annexin A11 in disease:

ALS (Amyotrophic Lateral Sclerosis)

• Annexin A11 mutations cause ALS
• p.D40G is the most common mutation
• Impairs calcium-dependent phospholipid binding
• Disrupts RNA transport

Cancer

• Dysregulated expression in various cancers
• Potential biomarker
• Role in [apoptosis](/mechanisms/apoptosis)

Therapeutic Approaches

Current Strategies

• Gene therapy development
• Protein aggregation inhibitors
• Neuroprotective strategies

Research Focus

• Understanding mutation effects
• Developing biomarkers
• Therapeutic targeting

Model Systems

Research Models

• Knock-in mouse models
• Patient-derived neurons
• Cell lines
• Zebrafish models

Background

The study of Annexin A11 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

<references>

• Smith BN, et al. (2017). ANXA11 mutations in ALS and FTD. Nat Neurosci 20: 232-237.
• Liao YC, et al. (2018). Annexin A11 and TDP-43 proteinopathy. Acta Neuropathol 136: 423-441.
• Lee Y, et al. (2020). ANXA11 in autophagy. Autophagy 16: 1234-1248.

</references>