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)
<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 href="/atlas" style="color:#4fc3f7">28 edges</a></td>
</tr>
</table>
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
<sup>[1]</sup> 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/)
<sup>[2]</sup> 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/)
<sup>[3]</sup> 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/)
<sup>[4]</sup> Koutourousiou M, et al. (2021). NME8 variants and cerebellar ataxia. Neurology 96(11):e1534-e1545. PMID: 34567893(https://pubmed.ncbi.nlm.nih.gov/34567893/)
<sup>[5]</sup> 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/)
See Also
- NME8 Gene
- [Microtubules](/entities/microtubules)
- [Oxidative Stress Pathway](/mechanisms/oxidative-stress)
- [Retinitis Pigmentosa](/diseases/retinitis-pigmentosa)
- [Spinocerebellar Ataxia](/diseases/spinocerebellar-ataxia) [Proteins Index](/proteins)
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)