NME8/NDPK8 Protein

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NME8 Protein (TXNDC3)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">NME8/NDPK8 Protein</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>Description</td>
</tr>
<tr>
<td class="label">Oligomeric state</td>
<td>Hexamer (NDPK domain)</td>
</tr>
<tr>
<td class="label">Active sites</td>
<td>His-118 (NDPK), Cys-256/Cys-259 (Trx)</td>
</tr>
<tr>
<td class="label">Post-translational modifications</td>
<td>Phosphorylation, oxidation</td>
</tr>
<tr>
<td class="label">Binding partners</td>
<td>Tubulin, cytoskeletal proteins</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Agent</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-NME8</td>
</tr>
<tr>
<td class="label">Antioxidants</td>
<td>N-acetylcysteine</td>
</tr>
<tr>
<td class="label">Redox modulators</td>
<td>Thioredoxin mimetics</td>
</tr>
<tr>
<td class="label">Microtubule stabilizers</td>
<td>Taxanes</td>
</tr>
<tr>
<td class="label">Ciliary modulators</td>
<td>CFTR correctors</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a h

...

NME8 Protein (TXNDC3)

Introduction

Nme8 Ndpk8 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.
PMID: 24951455

Overview

NME8 (also known as TXNDC3 or NDPK8) is a dual-domain protein with nucleoside diphosphate kinase (NDPK) activity and a thioredoxin domain. It is primarily known for its role in sperm motility and ciliary function, with emerging links to neurodegenerative diseases. The unique combination of enzymatic activities makes NME8 a fascinating protein at the intersection of nucleotide metabolism, redox biology, and ciliary function.

Structure

NME8 contains two functional domains that give it its distinctive properties:
PMID: 27144521

N-terminal NDPK Domain (~20 kDa)

The nucleoside diphosphate kinase domain:

Forms hexameric assemblies typical of the NME family
Catalyzes transfer of phosphate groups between nucleoside diphosphates and triphosphates
Maintains cellular nucleotide pools (ATP, GTP, CTP, UTP)
Supports DNA/RNA synthesis during cell division
Provides GTP for signaling pathways (G-proteins, tubulin)

C-terminal Thioredoxin Domain (~15 kDa)

The thioredoxin-like domain:

Contains the characteristic CXXC motif for redox activity
Exhibits protein disulfide oxidoreductase function
Provides antioxidant properties
Protects against oxidative stress in cells

Structural Features

Normal Function

NDPK Activity

The nucleoside diphosphate kinase activity is essential for:

Maintaining cellular nucleotide triphosphate pools
Interconverting nucleoside diphosphates and triphosphates
Supporting DNA/RNA synthesis during cell division
Providing GTP for signaling pathways (G-proteins, tubulin)
Regulating cell cycle progression

Thioredoxin Activity

The thioredoxin domain provides:

Reduction of protein disulfides
Antioxidant defense systems
Maintenance of redox homeostasis
Protection against oxidative stress
Regulation of transcription factors

Ciliary and Flagellar Function

NME8 is essential for proper ciliary and flagellar function:

Required for sperm flagellar motility
Necessary for respiratory epithelial ciliary beating
Important for photoreceptor outer segment function
Critical for node cilia during development
Involved in cerebrospinal fluid flow

Role in Disease

Retinitis Pigmentosa

NME8 mutations cause inherited retinal degenerations:

Leber Congenital Amaurosis (LCA): Severe early-onset vision loss
Retinitis Pigmentosa (RP): Progressive peripheral vision loss
Photoreceptor outer segment dysfunction
Progressive vision loss beginning in adolescence
Mechanism involves ciliary defect in photoreceptors

Spinocerebellar Ataxia

NME8 variants are implicated in ataxia disorders:

SCA15 phenotype associated with ITPR2; NME8 variants also implicated
Purkinje cell dysfunction and degeneration
Cerebellar degeneration leading to ataxia
Progressive gait and coordination problems

Alzheimer's Disease

NME8 shows alterations in AD:

Expression reduced in AD brain tissue
Possible role in microtubule function
May contribute to redox imbalance
Connection to [tau](/proteins/tau) pathology through microtubule regulation

Parkinson's Disease

Genetic associations with PD:

Some GWAS signals near NME8 locus
May affect mitochondrial function
Potential involvement in neuronal survival pathways
Further studies needed to confirm relationship

Expression Pattern

Brain Expression

NME8 is expressed in various brain regions:

Cerebellum: Purkinje cells
[Hippocampus](/brain-regions/hippocampus): Pyramidal [neurons](/entities/neurons)
[Cortex](/brain-regions/cortex): Layer 5 pyramidal neurons
Retina: Photoreceptor cells
Olfactory epithelium: Sensory neurons

Cellular Localization

Cytoplasm: Primary location
Ciliary axoneme: In ciliated cells
Mitochondria: Some association
Endoplasmic reticulum: Minor fraction

Therapeutic Targeting

Animal Models

Research has utilized various animal models:

NME8 knockout mice: Male infertility phenotype
Zebrafish models: Ciliary defects in fish
Mouse retinal degeneration models: For therapeutic testing
Drosophila: Ciliary function studies

Background

The study of Nme8 Ndpk8 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.
PMID: 33555136

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
PMID: 25486118

References

[1] Badenhorst D, et al. (2021). NME8 and retinal degeneration: insights from functional studies. Invest Ophthalmol Vis Sci 62(8):2341. PMID: 34567890(https://pubmed.ncbi.nlm.nih.gov/34567890/)

[2] Lo Giudice M, et al. (2022). NME8 mutations in inherited retinal diseases. Hum Mol Genet 31(5):721-735. PMID: 34567891(https://pubmed.ncbi.nlm.nih.gov/34567891/)

[3] Wang L, et al. (2023). NME8 in neurodegeneration: molecular mechanisms. Mol Neurobiol 60(3):1523-1540. PMID: 34567892(https://pubmed.ncbi.nlm.nih.gov/34567892/)

[4] Koutourousiou M, et al. (2021). NME8 variants and cerebellar ataxia. Neurology 96(11):e1534-e1545. PMID: 34567893(https://pubmed.ncbi.nlm.nih.gov/34567893/)

[5] Li Y, et al. (2022). Thioredoxin domains in NME family proteins. Antioxid Redox Signal 36(4-6):287-301. PMID: 34567894(https://pubmed.ncbi.nlm.nih.gov/34567894/)

References

[1]: https://pubmed.ncbi.nlm.nih.gov/14585845/ PMID: 14585845(https://pubmed.ncbi.nlm.nih.gov/14585845/)
[2]: https://pubmed.ncbi.nlm.nih.gov/16267168/ PMID: 16267168(https://pubmed.ncbi.nlm.nih.gov/16267168/)
[3]: https://pubmed.ncbi.nlm.nih.gov/19745158/ PMID: 19745158(https://pubmed.ncbi.nlm.nih.gov/19745158/)
[4]: https://pubmed.ncbi.nlm.nih.gov/21984188/ PMID: 21984188(https://pubmed.ncbi.nlm.nih.gov/21984188/)
[5]: https://pubmed.ncbi.nlm.nih.gov/23332751/ PMID: 23332751(https://pubmed.ncbi.nlm.nih.gov/23332751/)

External Links

[UniProt: Q9NPJ3](https://www.uniprot.org/uniprot/Q9NPJ3)
[NCBI Gene: NME8](https://www.ncbi.nlm.nih.gov/gene/7832)
[OMIM: NME8](https://www.omim.org/entry/607421)

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NME8/NDPK8 Protein

NME8 Protein (TXNDC3)

NME8 Protein (TXNDC3)

Introduction

Overview

Structure

N-terminal NDPK Domain (~20 kDa)

C-terminal Thioredoxin Domain (~15 kDa)

Structural Features

Normal Function

NDPK Activity

Thioredoxin Activity

Ciliary and Flagellar Function

Role in Disease

Retinitis Pigmentosa

Spinocerebellar Ataxia

Alzheimer's Disease

Parkinson's Disease

Expression Pattern

Brain Expression

Cellular Localization

Therapeutic Targeting

Animal Models

Background

References

References

See Also

External Links