PSD-93 Protein

PSD93 (DLG3)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PSD-93 Protein</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DLG3</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Discs Large Homolog 3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1749</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165646</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q92796</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

PSD93 (Postsynaptic Density Protein of 93 kDa), encoded by the DLG3 gene, is a member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins. It plays a critical role in the organization of postsynaptic density complexes at excitatory synapses and has been implicated in synaptic plasticity, learning, and memory[@kim2004].

Gene Information

Protein Structure and Function

Domain Architecture

PSD93 contains multiple protein-protein interaction domains:

PSD93 (DLG3)

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PSD-93 Protein</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>DLG3</td>
</tr>
<tr>
<td class="label">Official Name</td>
<td>Discs Large Homolog 3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>Xq13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1749</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000165646</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q92796</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Overview

PSD93 (Postsynaptic Density Protein of 93 kDa), encoded by the DLG3 gene, is a member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins. It plays a critical role in the organization of postsynaptic density complexes at excitatory synapses and has been implicated in synaptic plasticity, learning, and memory[@kim2004].

Gene Information

Protein Structure and Function

Domain Architecture

PSD93 contains multiple protein-protein interaction domains:

• N-terminal region: Palmitoylation site for membrane targeting
• PDZ domains (3x): PDZ1-3 mediate interactions with [NMDA receptor](/entities/nmda-receptor) subunits (NR2A/B), AMPA receptor subunits, and other synaptic proteins
• SH3 domain: Binds to proline-rich motifs
• Guanylate kinase (GK) domain: Catalytic domain with binding sites for GKAP/SAP90

Synaptic Scaffolding

PSD93 is a core component of the postsynaptic density (PSD) scaffold, forming a complex network with:

• NMDA receptors (via PDZ domains)
• AMPA receptors (via PDZ interactions with GRIP/ABP)
• Kainate receptors
• Shank proteins (connecting to actin cytoskeleton)
• CRASH/Cortactin (actin remodeling)

Role in Neurodegeneration

Alzheimer's Disease

In AD, PSD93 alterations contribute to synaptic dysfunction through multiple mechanisms[@coley2020]:

Parkinson's Disease

PSD93 has been implicated in PD through[@jiang2019]:

• Dopaminergic synapse function: Role in maintaining dopaminergic synaptic architecture
• Excitotoxicity: Interaction with NMDA receptors may contribute to excitotoxic cell death
• Mitochondrial dysfunction: Possible connections to mitochondrial quality control pathways

Amyotrophic Lateral Sclerosis

In ALS, PSD93 may play a role in[@synaptic2020]:

• Motor neuron synaptic stability: Disruption of neuromuscular junction integrity
• Excitotoxicity: Altered glutamate receptor dynamics
• Axonal transport: Connections to cytoskeletal regulatory proteins

Expression Pattern

Brain Regions

• Cerebral [cortex](/brain-regions/cortex): High expression in layers II-III and V
• [Hippocampus](/brain-regions/hippocampus): Strong expression in CA1 and dentate gyrus
• Striatum: Moderate expression in medium spiny [neurons](/entities/neurons)
• Cerebellum: Purkinje cell expression
• Brainstem: Moderate expression

Cell Type Specificity

• Neurons: Primary expression in excitatory (glutamatergic) neurons
• [Astrocytes](/entities/astrocytes): Low expression
• [Microglia](/cell-types/microglia-neuroinflammation): Minimal expression
• Oligodendrocytes: Not expressed

Therapeutic Implications

Drug Targets

• PSD93-NMDAR interaction inhibitors: Potential neuroprotective agents
• PSD93 stability modulators: Enhance synaptic resilience
• PDZ domain modulators: Target protein-protein interactions

Biomarker Potential

• CSF PSD93 levels: Possible biomarker for synaptic loss
• Postmortem brain tissue: Diagnostic aid for synaptic pathology

Clinical Significance

Associated Conditions

• X-linked mental retardation: DLG3 mutations associated with non-syndromic intellectual disability[@tarpey2004]
• Epilepsy: Altered PSD93 expression in epileptic tissue
• Schizophrenia: Reduced PSD93 in prefrontal cortex
• Neurodevelopmental disorders: Synaptic scaffolding abnormalities

See Also

• [DLG3 Gene](/genes/dlg2)

External Links

• [Ensembl: ENSG00000165646](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000165646)
• [GeneCards: DLG3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DLG3)

Related Proteins

• PSD95 (DLG4) — Closely related MAGUK family member
• DLG2 — Another PSD93 homolog
• Shank3 — Postsynaptic scaffold interactor
• GRIP1 — AMPA receptor interacting protein
• NR2A (GRIN2A) — NMDA receptor subunit
• NR2B (GRIN2B) — NMDA receptor subunit

References