Nop56 Protein

Nop56 (Nucleolar Protein 56)

Introduction

Nop56 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

<div class="infobox infobox-protein"> [@ishihara2021]
<table> [@ouyang2020]
<tr><th>Protein Name</th><td>Nop56</td></tr> [@nakam]
<tr><th>Gene</th><td>[NOP56](/genes/nop56)</td></tr>
<tr><th>UniProt ID</th><td>[O00447](https://www.uniprot.org/uniprot/O00447)</td></tr>
<tr><th>PDB Structure</th><td>3LWZ, 5XBM</td></tr>
<tr><th>Molecular Weight</th><td>~66 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Nucleolus</td></tr>
<tr><th>Protein Family</th><td>Box C/D snoRNP family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Structure

Nop56 is a core component of box C/D snoRNPs:

Domain Organization

• N-terminal domain: Protein interactions
• Central domain: Coiled-coil for oligomerization
• C-terminal domain: NOP domain (RNA binding)
• GAR domain: Arginine-glycine rich

SnoRNP Complex

Part of the box C/D snoRNP particle:

• Core proteins: Nop56, Nop58, fibrillarin (FLPN)
• snoRNA: Guide RNAs (SNORDs)
• Assembly factors: SNU13, RUVBL1/2

Normal Function

Nop56 is essential for ribosome biogenesis:

Pre-rRNA Processing

• 2'-O-methylation of ribose (site-specific)
• Assembly of active snoRNP complexes
• Processing of 18S rRNA (40S subunit)

...

Nop56 (Nucleolar Protein 56)

Introduction

Nop56 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

<div class="infobox infobox-protein"> [@ishihara2021]
<table> [@ouyang2020]
<tr><th>Protein Name</th><td>Nop56</td></tr> [@nakam]
<tr><th>Gene</th><td>[NOP56](/genes/nop56)</td></tr>
<tr><th>UniProt ID</th><td>[O00447](https://www.uniprot.org/uniprot/O00447)</td></tr>
<tr><th>PDB Structure</th><td>3LWZ, 5XBM</td></tr>
<tr><th>Molecular Weight</th><td>~66 kDa</td></tr>
<tr><th>Subcellular Localization</th><td>Nucleolus</td></tr>
<tr><th>Protein Family</th><td>Box C/D snoRNP family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Structure

Nop56 is a core component of box C/D snoRNPs:

Domain Organization

• N-terminal domain: Protein interactions
• Central domain: Coiled-coil for oligomerization
• C-terminal domain: NOP domain (RNA binding)
• GAR domain: Arginine-glycine rich

SnoRNP Complex

Part of the box C/D snoRNP particle:

• Core proteins: Nop56, Nop58, fibrillarin (FLPN)
• snoRNA: Guide RNAs (SNORDs)
• Assembly factors: SNU13, RUVBL1/2

Normal Function

Nop56 is essential for ribosome biogenesis:

Pre-rRNA Processing

• 2'-O-methylation of ribose (site-specific)
• Assembly of active snoRNP complexes
• Processing of 18S rRNA (40S subunit)

Neuronal Function

• Essential for neuronal protein synthesis
• Maintains nucleolar integrity
• Supports cell survival

Role in Disease

Spinocerebellar Ataxia Type 36 (SCA36)

GGCCTG hexanucleotide repeat expansion in NOP56 causes SCA36:

Pathogenic Mechanisms:

• RNA foci formation in nucleus
• Sequestration of RNA-binding proteins
• Disrupted RNA processing
• Cerebellar and motor neuron degeneration

Repeat Expansion Effects:

• Normal: < 15 repeats
• Pathogenic: > 18-500+ repeats
• Anticipation in families

Neurodegeneration

• Motor neuron vulnerability
• Cerebellar Purkinje cell loss
• Dorsal root ganglion involvement

Therapeutic Targeting

RNA-Targeted Therapies

• Antisense oligonucleotides: Target expanded repeat RNA
• RNAi: Silence mutant allele expression
• Small molecules: Disperse RNA foci

Gene Therapy

• CRISPR-based approaches
• AAV-delivered gene therapy

Key Publications

Arai T et al. (2011). "SCA36 and NOP56 expansion." Neurology. PMID: 21810694(https://pubmed.ncbi.nlm.nih.gov/21810694/)

García-Murias M et al. (2012). "SCA36 hexanucleotide expansion." Hum Mol Genet. PMID: 22536397(https://pubmed.ncbi.nlm.nih.gov/22536397/)

Kobayashi H et al. (2020). "RNA pathology in SCA36." Acta Neuropathol. PMID: 32086513(https://pubmed.ncbi.nlm.nih.gov/32086513/)

Clinical Presentation

SCA36 has characteristic features:

Motor Symptoms

• Progressive ataxia (gait instability)
• Dysarthria (slurred speech)
• Nystagmus (involuntary eye movements)
• Hyperreflexia in later stages

Non-Motor Symptoms

• Hearing loss (cochlear involvement)
• Muscle fasciculations
• Mild cognitive impairment in some cases
• Sleep disturbances

Disease Progression

• Age of onset: 40-60 years
• Slow progression over decades
• Wheelchair dependence in advanced stages
• Life expectancy typically normal

Research Directions

Current Studies

• Understanding RNA toxicity mechanisms
• Biomarker development for repeat length
• Natural history studies
• Therapeutic target identification

Model Systems

• Mouse models with expanded repeats
• Yeast models for toxicity screening
• Patient-derived [neurons](/entities/neurons)
• Zebrafish models

Protein Interactions

Nop56 interacts with key proteins:

| Partner | Interaction | Function |
|---------|-------------|----------|
| Nop58 | Heterodimer | SnoRNP core formation |
| Fibrillarin | Complex | rRNA methylation |
| SNU13 | Binding | snoRNP assembly |
| RUVBL1/2 | ATPase | Assembly chaperone |

Background

The study of Nop56 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.

References

[@nakam]: Nakam

See Also

• [NOP56 Gene](/genes/nop56)
• [Spinocerebellar Ataxia](/cell-types/cerebellar-purkinje-ataxia)
• [RNA Metabolism Dysregulation](/mechanisms/rna-metabolism-dysregulation)
• [Ribosome Biogenesis](/content/genes)
• [UniProt: O00447](https://www.uniprot.org/uniprot/O00447)
• [RCSB PDB: 3LWZ](https://www.rcsb.org/structure/3LWZ)
• [GeneReviews: SCA36](https://www.ncbi.nlm.nih.gov/books/NBK231487/)

NeuroWiki - Protein Page | Last Updated: 2026-03-04