Ataxin-10 Protein

Ataxin-10 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Ataxin-10 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Ataxin-10</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>ATXN10</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBB6</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~47 kDa (420 amino acids)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, nucleus ( shuttles between compartments)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Ataxin family (non-aggregating)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>High in cerebellum (Purkinje cells), cerebral [cortex](/brain-regions/cortex), brainstem</td>
</tr>
</table>

Ataxin 10 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.

Ataxin-10 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Ataxin-10 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Ataxin-10</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>ATXN10</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9UBB6</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~47 kDa (420 amino acids)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, nucleus ( shuttles between compartments)</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Ataxin family (non-aggregating)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>High in cerebellum (Purkinje cells), cerebral [cortex](/brain-regions/cortex), brainstem</td>
</tr>
</table>

Ataxin 10 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.

Ataxin-10 is the protein encoded by the ATXN10 gene, located on chromosome 22q13.31. It is associated with spinocerebellar ataxia type 10 (SCA10), a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia, dysarthria, and seizures. Ataxin-10 is expressed ubiquitously in the brain, with particularly high expression in cerebellar Purkinje cells, which are the primary neuronal lost population in SCA10. The protein contains multiple HEAT repeat domains that mediate protein-protein interactions, suggesting it functions as a scaffold or regulatory protein rather than having catalytic activity. [@teive2014]

Overview

Ataxin-10 is a neuronal protein that plays a critical role in cerebellar function and survival. While its exact physiological function remains incompletely characterized, evidence suggests it acts as a survival factor for Purkinje cells and participates in various cellular processes including signal transduction, mRNA translation regulation, and stress response pathways. SCA10 is unique among spinocerebellar ataxias due to its characteristic pentanucleotide repeat expansion in the ATXN10 gene, which leads to both loss-of-function effects and toxic gain-of-function mechanisms. The disease primarily affects the cerebellum and brainstem, leading to progressive motor impairment, but can also involve extracerebellar features including epilepsy and peripheral neuropathy. [@chen2017]

Basic Information

Structure

Ataxin-10 has a relatively simple but distinctive structure:

• HEAT repeats: 6-7 HEAT ([Huntingtin](/proteins/huntingtin-protein), Elongation factor 3, [PP2A](/entities/pp2a), TOR1) repeat motifs throughout the protein
• Alpha-helical content: Predominantly alpha-helical secondary structure
• NLS/NES sequences: Nuclear localization and export signals for nucleocytoplasmic shuttling
• No known catalytic domains: Functions as a scaffolding/regulatory protein
• Disordered regions: Contains intrinsically disordered regions that may mediate interactions

Comparison with Other Ataxins

Unlike many other ataxins (such as ataxin-1, ataxin-3, and ataxin-7), ataxin-10 does not form nuclear inclusions in disease, which may reflect different pathogenic mechanisms.

Normal Function

The normal physiological functions of ataxin-10 are still being elucidated, but research has identified several important roles:

Neuronal Survival Factor

• Essential for Purkinje cell viability: Deletion of ATXN10 in mice leads to Purkinje cell degeneration
• Anti-apoptotic function: Protects [neurons](/entities/neurons) from various apoptotic stimuli
• Mitochondrial function: May help maintain mitochondrial homeostasis in neurons

Signal Transduction

• Modulates various intracellular signaling pathways
• May interact with neuronal calcium sensor proteins
• Potential role in phosphatidylinositol signaling

Translational Regulation

• Some evidence for association with translation initiation factors
• May regulate translation of specific mRNAs in neurons
• Could influence protein synthesis required for synaptic plasticity

Stress Response

• Induced by cellular stress conditions
• May participate in the cellular response to oxidative stress
• Potential role in protein quality control pathways

Role in Disease

Spinocerebellar Ataxia Type 10 (SCA10)

SCA10 is a pentanucleotide repeat expansion disorder caused by expansion of an ATTCT repeat in intron 1 of the ATXN10 gene:

• Normal repeat length: 8-32 ATTCT repeats
• Pathogenic repeat length: 800-4,500 ATTCT repeats (uninterrupted expansion)
• Anticipation: Earlier onset in successive generations (anticipation)
• Founder effect: Predominant in Latin American populations (Mexican, Brazilian, Argentine)

Pathogenic Mechanisms

The disease results from a combination of toxic gain-of-function and loss-of-function mechanisms:

RNA Toxicity

• Expanded ATTCT repeats form abnormal hairpin structures in RNA
• These structures sequester RNA-binding proteins
• Disrupts normal RNA processing and splicing

• Translation initiates from the expanded repeat without an AUG codon
• Produces toxic polyglutamine and polyalanine-containing peptides
• These peptides may contribute to neurodegeneration

• Expanded repeat may reduce ATXN10 expression through various mechanisms
• Haploinsufficiency may contribute to disease phenotype
• Ataxin-10 reduction leads to Purkinje cell vulnerability

Clinical Features

SCA10 presents with characteristic neurological symptoms:

• Progressive cerebellar ataxia: Gait instability, limb incoordination
• Dysarthria: Slurred speech due to cerebellar dysarthria
• Seizures: Occur in approximately 50% of patients (focal, generalized)
• Cognitive impairment: Mild cognitive deficits in some patients
• Peripheral neuropathy: Sensory neuropathy in advanced cases
• Oculomotor abnormalities: Nystagmus, saccadic pursuits

Therapeutic Strategies

Currently no disease-modifying treatments exist, but several approaches are under investigation:

• RNA toxicity mitigation: Compounds targeting toxic RNA structures
• RAN translation inhibitors: Drugs to block non-AUG translation
• Gene silencing: ASOs to reduce toxic repeat-containing RNA
• Neuroprotective agents: Compounds to support Purkinje cell survival
• Symptomatic management: Antiepileptic drugs, physical therapy

Key Publications

See Also

• [ATXN10 Gene](/proteins/atxn10-protein) - ATXN10 gene page
• [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia) - SCA disease category
• [Purkinje Cells](/cell-types/purkinje-cells) - Primary affected neuron type
• [Cerebellar Degeneration](/mechanisms/cerebellar-degeneration) - Degeneration mechanisms
• [Repeat Expansion Disorders](/trinucleotide-repeat-expansion-disorders) - Disease mechanism

Background

The study of Ataxin 10 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

Brain Atlas Resources

• [Allen Human Brain Atlas - Ataxin-10 Expression](https://human.brain-map.org/microarray/search/show?search_term=Ataxin-10)
• [Allen Cell Type Atlas - Ataxin-10](https://celltypes.brain-map.org/)
• [BrainSpan - Ataxin-10 Developmental Expression](https://brainspan.org/)
• [Allen Mouse Brain Atlas - Ataxin-10](https://mouse.brain-map.org/)
• [UniProt: Q9UBB6](https://www.uniprot.org/uniprot/Q9UBB6)
• [NCBI Gene: ATXN10](https://www.ncbi.nlm.nih.gov/gene/4720)
• [OMIM: SCA10](https://www.omim.org/entry/603516)
• [GeneReviews: SCA10](https://www.ncbi.nlm.nih.gov/books/NBK1116/)

References