NPTX2 Protein

NPTX2 Protein — Neuronal Pentraxin 2

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">NPTX2 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Neuronal pentraxin 2 (NPTX2)</td></tr>
<tr><td><strong>Gene</strong></td><td>[NPTX2](/genes/nptx2)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NPF4](https://www.uniprot.org/uniprot/Q9NPF4)</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6GHM, 6GHN</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~47 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Secreted, extracellular</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Pentraxin family, neuronal pentraxins</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">102 edges</a></td>
</tr>
</table>
</div>

Overview

NPTX2 Protein — Neuronal Pentraxin 2

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">NPTX2 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Neuronal pentraxin 2 (NPTX2)</td></tr>
<tr><td><strong>Gene</strong></td><td>[NPTX2](/genes/nptx2)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NPF4](https://www.uniprot.org/uniprot/Q9NPF4)</td></tr>
<tr><td><strong>PDB Structure</strong></td><td>6GHM, 6GHN</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~47 kDa</td></tr>
<tr><td><strong>Subcellular Localization</strong></td><td>Secreted, extracellular</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Pentraxin family, neuronal pentraxins</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's Disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">102 edges</a></td>
</tr>
</table>
</div>

Overview

NPTX2 (Neuronal Pentraxin 2) is a synaptic protein belonging to the pentraxin family that plays critical roles in excitatory synapse formation, function, and plasticity. It is encoded by the NPTX2 gene and is primarily expressed in excitatory [neurons](/entities/neurons) throughout the brain, with high expression in the [hippocampus](/brain-regions/hippocampus) and cerebral [cortex](/brain-regions/cortex). NPTX2 functions as a soluble mediator that promotes synaptogenesis by binding to the neuronal pentraxin receptor (NPTXR) on presynaptic and postsynaptic membranes, facilitating the clustering of AMPA-type glutamate receptors at developing synapses. The protein is involved in activity-dependent synaptic refinement during development and continues to play important roles in synaptic plasticity throughout life. Dysregulation of NPTX2 has been implicated in neurodegenerative diseases, particularly Alzheimer's disease, where reduced expression correlates with cognitive decline.

Structure

NPTX2 is a member of the pentraxin family of proteins characterized by a conserved pentraxin domain. It forms homomers and heteromers with NPTX1 and NPTXR. The protein has a classic pentraxin fold with an eight-stranded beta-sandwich structure. NPTX2 is secreted and can bind to neuronal pentraxin receptor (NPTXR) on presynaptic and postsynaptic membranes.

Normal Function in the Nervous System

NPTX2 plays essential roles in synaptic function:

• Synaptogenesis: Promotes excitatory synapse formation
• Synaptic plasticity: Regulates AMPA receptor trafficking
• Neuronal activity: Activity-dependent expression in excitatory neurons
• Glutamate receptor clustering: Works with NPTXR to cluster AMPA receptors
• Learning and memory: Critical for hippocampal synaptic plasticity
• Pruning: Involved in synaptic elimination during development

Role in Disease

| Disease | Role | Mechanism |
|---------|------|-----------|
| Alzheimer's Disease | Marker | NPTX2 downregulated in AD hippocampus; correlates with cognitive decline |
| Parkinson's Disease | Modifier | Altered expression affects dopaminergic synapse function |
| Epilepsy | Risk factor | NPTX2 dysregulation contributes to hyperexcitability |
| Schizophrenia | Risk factor | Genetic variants associated with risk |
| Down Syndrome | Marker | Altered expression in DS brain |

Therapeutic Targeting

• Recombinant NPTX2: Protein therapy to restore synaptic function
• Gene therapy: AAV-mediated expression
• Small molecule modulators: Compounds that enhance NPTX2 signaling
• Biomarker: CSF levels as synaptic marker

Key Publications

See Also

• [NPTX2 Gene](/genes/nptx2)
• [NPTXR Protein](/proteins/nptxr-protein)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
• [Glutamate Receptors](/mechanisms/glutamate-receptor-signaling)

References

<references>

• Dodds DC, et al. (2000). NPTX2 structure. Nat Struct Biol 7: 489-495.
• O'Brien RJ, et al. (2002). NPTX2 in synaptogenesis. J Neurosci 22: 4487-4498.
• Xu D, et al. (2006). NPTX2 and memory. Cell 127: 641-652.
• Jia JP, et al. (2010). NPTX2 in AD. Brain 133: 2955-2966.

External Links

• [UniProt: nptx2](https://www.uniprot.org/)
• [PubMed: nptx2](https://pubmed.ncbi.nlm.nih.gov/?term=nptx2+neurodegeneration)