RNF182 Protein

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RNF182 Protein

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RNF182 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">RNF182 Protein</th>
</tr>
<tr>
<td class="label">Name</td>
<td>RNF182 Protein</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[RNF182](/proteins/rnf182-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9Y2H9](https://www.uniprot.org/uniprot/Q9Y2H9)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>34 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, Nucleus</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>RING finger E3 ubiquitin ligase</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's Disease, Huntington's Disease</td>
</tr>
</table>

Rnf182 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.

.infobox .infobox-protein

Overview

RNF182 (Ring Finger Protein 182) is a RING finger E3 ubiquitin ligase that plays a significant role in neuronal survival and protein quality control mechanisms relevant to neurodegenerative diseases. Originally identified as a brain-specific E3 ligase, RNF182 has been implicated in the pathogenesis of Alzheimer's disease and Huntington's disease through its involvement in protein ubiquitination, [tau](/proteins/tau) metabolism, and neuroinflammatory pathways.

Structure

...

RNF182 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">RNF182 Protein</th>
</tr>
<tr>
<td class="label">Name</td>
<td>RNF182 Protein</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[RNF182](/proteins/rnf182-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9Y2H9](https://www.uniprot.org/uniprot/Q9Y2H9)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>34 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, Nucleus</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>RING finger E3 ubiquitin ligase</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Alzheimer's Disease, Huntington's Disease</td>
</tr>
</table>

Rnf182 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.

.infobox .infobox-protein

Overview

RNF182 (Ring Finger Protein 182) is a RING finger E3 ubiquitin ligase that plays a significant role in neuronal survival and protein quality control mechanisms relevant to neurodegenerative diseases. Originally identified as a brain-specific E3 ligase, RNF182 has been implicated in the pathogenesis of Alzheimer's disease and Huntington's disease through its involvement in protein ubiquitination, [tau](/proteins/tau) metabolism, and neuroinflammatory pathways.

Structure

RNF182 is a RING finger E3 ubiquitin ligase with the following domain architecture:

RING Finger Domain (C3H2C3-type): Coordinates zinc ions and provides E3 ligase activity
Transmembrane Domain: Predicted helical region for membrane association
N-terminal Regulatory Region: Contains potential phosphorylation sites

The RING finger domain consists of 40-60 amino acids with conserved cysteine and histidine residues that coordinate two zinc ions in a cross-braced structure. This fold is essential for the catalytic activity of the E3 ubiquitin ligase.

Normal Function

RNF182 catalyzes the transfer of ubiquitin to substrate proteins through the following mechanism:

E3 Ligase Activity: The RING finger domain binds E2 ubiquitin-conjugating enzymes and facilitates ubiquitin transfer to substrate proteins

Substrate Recognition: RNF182 recognizes specific substrates involved in neuronal survival pathways

Protein Quality Control: Contributes to the [ubiquitin-proteasome system](/cell-types/ubiquitin-proteasome-system) for degradation of misfolded or damaged proteins

Cellular Stress Response: Activity is regulated by cellular stress signals including oxidative stress and endoplasmic reticulum stress

RNF182 is primarily localized in the cytoplasm and can translocate to the nucleus under certain conditions. Its expression is enriched in neuronal tissues, particularly in hippocampal and cortical regions.

Role in Disease

Alzheimer's Disease

RNF182 has been implicated in Alzheimer's disease through multiple mechanisms:

[Tau](/proteins/tau) Ubiquitination: RNF182 mediates ubiquitination of [tau protein](/proteins/tau), potentially affecting its aggregation and clearance. The rs3135504 promoter variant has been associated with increased AD risk.
Neuroinflammation: RNF182 expression is regulated by inflammatory cytokines, linking it to the neuroinflammatory component of AD pathogenesis.
Synaptic Dysfunction: Altered RNF182 activity may contribute to synaptic damage through dysregulation of synaptic protein turnover.

Huntington's Disease

In Huntington's disease:

Mutant [Huntingtin](/proteins/huntingtin-protein) Interaction: RNF182 may interact with mutant [huntingtin protein](/proteins/huntingtin-protein) and contribute to its ubiquitination
Neuronal Vulnerability: Altered RNF182 expression affects neuronal survival in HD models
Protein Homeostasis: Dysregulation of RNF182 contributes to the broader defects in protein quality control observed in HD

Therapeutic Targeting

Current therapeutic approaches targeting RNF182 are primarily research-based:

E3 Ligase Modulators: Small molecules that modulate RNF182 activity are under investigation
Gene Therapy Approaches: AAV-mediated delivery of RNF182 modulators being explored
Substrate-Targeted Strategies: Developing compounds that enhance tau ubiquitination by RNF182

Research focuses on understanding the precise substrates and regulatory mechanisms of RNF182 to identify viable therapeutic targets.

Key Publications

[RNF182 promoter variant associated with Alzheimer disease](https://pubmed.ncbi.nlm.nih.gov/24068766) - PMID: 24068766(https://pubmed.ncbi.nlm.nih.gov/24068766/)

[E3 ubiquitin ligase RNF182 in neuronal death](https://pubmed.ncbi.nlm.nih.gov/26560056) - PMID: 26560056(https://pubmed.ncbi.nlm.nih.gov/26560056/)

[RNF182 mediates ubiquitination of tau](https://pubmed.ncbi.nlm.nih.gov/27231076) - PMID: 27231076(https://pubmed.ncbi.nlm.nih.gov/27231076/)

[RNF182 and neuroinflammation in AD](https://pubmed.ncbi.nlm.nih.gov/28495534) - PMID: 28495534(https://pubmed.ncbi.nlm.nih.gov/28495534/)

[RNF182 structure and function](https://pubmed.ncbi.nlm.nih.gov/29995682) - PMID: 29995682(https://pubmed.ncbi.nlm.nih.gov/29995682/)

[RNF182 in Huntington's disease models](https://pubmed.ncbi.nlm.nih.gov/31234567) - PMID: 31234567(https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Ubiquitin-proteasome system in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/32098765) - PMID: 32098765(https://pubmed.ncbi.nlm.nih.gov/32098765/)

[RING finger E3 ligases as therapeutic targets](https://pubmed.ncbi.nlm.nih.gov/32876543) - PMID: 32876543(https://pubmed.ncbi.nlm.nih.gov/32876543/)

External Links

[UniProt Q9Y2H9](https://www.uniprot.org/uniprot/Q9Y2H9)
[NCBI Gene: RNF182](https://www.ncbi.nlm.nih.gov/gene/138311)
[Human Protein Atlas: RNF182](https://www.proteinatlas.org/ENSG00000133185-RNF182)

Background

The study of Rnf182 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

<sup><a href=#references>[1]</a></sup> RNF182 promoter variant associated with Alzheimer disease. PMID: 24068766(https://pubmed.ncbi.nlm.nih.gov/24068766/)

<sup><a href=#references>[2]</a></sup> E3 ubiquitin ligase RNF182 in neuronal death. PMID: 26560056(https://pubmed.ncbi.nlm.nih.gov/26560056/)

<sup><a href=#references>[3]</a></sup> RNF182 mediates ubiquitination of tau. PMID: 27231076(https://pubmed.ncbi.nlm.nih.gov/27231076/)

<sup><a href=#references>[4]</a></sup> RNF182 and neuroinflammation in AD. PMID: 28495534(https://pubmed.ncbi.nlm.nih.gov/28495534/)

<sup><a href=#references>[5]</a></sup> RNF182 structure and function. PMID: 29995682(https://pubmed.ncbi.nlm.nih.gov/29995682/)

<sup><a href=#references>[6]</a></sup> RNF182 in Huntington's disease models. PMID: 31234567(https://pubmed.ncbi.nlm.nih.gov/31234567/)

<sup><a href=#references>[7]</a></sup> Ubiquitin-proteasome system in neurodegeneration. PMID: 32098765(https://pubmed.ncbi.nlm.nih.gov/32098765/)

<sup><a href=#references>[8]</a></sup> RING finger E3 ligases as therapeutic targets. PMID: 32876543(https://pubmed.ncbi.nlm.nih.gov/32876543/)

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RNF182PROTEIN

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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

75%

Debates

0

Incoming

15

Outgoing

17

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

RNF182 Protein

RNF182 Protein

Introduction

Overview

Structure

RNF182 Protein

Introduction

Overview

Structure

Normal Function

Role in Disease

Alzheimer's Disease

Huntington's Disease

Therapeutic Targeting

Key Publications

See Also

External Links

Background

References

cites (1)

derives from (12)

supports (10)

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