ANXA11 Protein — Annexin A11

ANXA11 Protein — Annexin A11

Introduction

Anxa11 Protein — Annexin A11 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

ANXA11 Protein — Annexin A11

Introduction

Anxa11 Protein — Annexin A11 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

<div class="infobox infobox-protein"> [@supsup2020]
<h3>ANXA11 Protein</h3>
<table>
<tr><th>Protein Name</th><td>Annexin A11</td></tr>
<tr><th>Gene</th><td>[ANXA11](/genes/anxa11)</td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/P50995">P50995</a></td></tr>
<tr><th>Protein Size</th><td>505 amino acids (~54 kDa)</td></tr>
<tr><th>Subcellular Localization</th><td>Cytoplasm; nucleus; plasma membrane; cytoskeleton</td></tr>
<tr><th>Protein Family</th><td>Annexin family (calcium-dependent phospholipid-binding proteins)</td></tr>
<tr><th>PDB Structures</th><td><a href="https://www.ebi.ac.uk/pdbe/search/pdb/1HMH">1HMH</a>, <a href="https://www.ebi.ac.uk/pdbe/search/pdb/1XJL">1XJL</a></td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/igg4-related-cholangitis" style="color:#ef9a9a">IgG4-related cholangitis</a>, <a href="/wiki/neurodegenerative-diseases" style="color:#ef9a9a">NEURODEGENERATIVE DISEASES</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">amyotrophic lateral sclerosis</a>, <a href="/wiki/bladder-cancer" style="color:#ef9a9a">bladder cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">18 edges</a></td>
</tr>
</table>
</div>

Annexin A11 (ANXA11) is a calcium-dependent phospholipid-binding protein that plays important roles in membrane organization, vesicle trafficking, and more recently has been implicated in the pathogenesis of ALS and other neurodegenerative diseases.

Structure

ANXA11 has a characteristic annexin domain structure:

• N-terminal unique region: First 30-40 amino acids, contains theALS-associated mutation site (D40G)
• Core domain: Four annexin repeats (each ~70 amino acids) that form the calcium-dependent phospholipid-binding pocket
• Type II Ca2+ binding sites: Multiple calcium-binding motifs that mediate phospholipid binding

Normal Function

In normal cells, ANXA11 functions in:

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

ANXA11 was identified as an ALS susceptibility gene through GWAS^[1]. Pathogenic mutations (e.g., D40G, R235C, G38R) disrupt the normal function of ANXA11 in several ways:

• Altered Calcium Binding: Mutations in the N-terminal region affect calcium-dependent membrane binding
• Impaired Vesicle Transport: Mutant ANXA11 disrupts axonal vesicle trafficking, contributing to motor neuron degeneration
• Aggregation Propensity: Some mutations increase the tendency of ANXA11 to form protein aggregates
• Stress Granule Dysregulation: ANXA11 localizes to stress granules, and ALS mutations alter this localization^[2]

Frontotemporal Dementia (FTD)

ANXA11 mutations have also been reported in FTD cases, suggesting a shared pathomechanism with ALS.

Alzheimer's Disease

ANXA11 is upregulated in AD brains and may contribute to altered membrane dynamics and inflammation.

Therapeutic Targeting

No specific ANXA11-targeted therapies exist yet, but strategies under investigation include:

• Small Molecule Stabilizers: Compounds that stabilize normal ANXA11 conformation
• RNAi/ASO: Gene silencing approaches to reduce mutant protein expression
• Protein-Protein Interaction Inhibitors: Blocking interactions with stress granule proteins

Interactions

ANXA11 interacts with:

• Calcyclin (S100A6): Calcium-binding protein that modulates ANXA11 function
• Actin: Cytoskeletal protein for membrane organization
• 14-3-3 proteins: Adaptor proteins that regulate ANXA11 localization
• SMN complex: Involved in mRNA processing; relevance to ALS

See Also

• [ANXA11 Gene](/genes/anxa11)
• [ALS Genes](/diseases/amyotrophic-lateral-sclerosis)
• [Stress Granules in Neurodegeneration](/mechanisms/stress-granules)
• [Annexin Family](/proteins/annexin-a1)
• [Actin Cytoskeleton in Neurons](/mechanisms/cytoskeleton-dynamics)

Background

The study of Anxa11 Protein — Annexin A11 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

PMID: 30636468(https://pubmed.ncbi.nlm.nih.gov/30636468/) PMID: 32482997(https://pubmed.ncbi.nlm.nih.gov/32482997/)