HOMER3 — Homer Scaffold Protein 3

HOMER3 Gene — Homer Scaffold Protein 3

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HOMER3 — Homer Scaffold Protein 3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>HOMER3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Homer Scaffold Protein 3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>84524</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604001</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000150773</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NKUC6</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>354 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~40 kDa</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">mGluR1/5</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">IP3R1</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">PSD-95</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Shank</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Rheb</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

HOMER3 Gene — Homer Scaffold Protein 3

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">HOMER3 — Homer Scaffold Protein 3</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>HOMER3</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Homer Scaffold Protein 3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19p13.11</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>84524</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604001</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000150773</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9NKUC6</td>
</tr>
<tr>
<td class="label">Protein Size</td>
<td>354 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~40 kDa</td>
</tr>
<tr>
<td class="label">Protein</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">mGluR1/5</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">IP3R1</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">PSD-95</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Shank</td>
<td>Indirect</td>
</tr>
<tr>
<td class="label">Rheb</td>
<td>Direct binding</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

The HOMER3 gene (Homer Scaffold Protein 3) encodes a member of the Homer family of postsynaptic density (PSD) scaffold proteins. HOMER3 plays critical roles in synapse formation, synaptic plasticity, and neuronal signaling by linking metabotropic glutamate receptors (mGluRs) to intracellular signaling pathways and the actin cytoskeleton[@brakeman1997]. Dysregulation of HOMER proteins is implicated in various neurological disorders including Alzheimer's disease, schizophrenia, and autism spectrum disorders.

Gene Information

Protein Structure

HOMER proteins contain two main functional domains:

• N-terminal Ena/VASP Homology 1 (EVH1) domain: Binds to proline-rich motifs in target proteins, particularly the PPXXF motif found in mGluRs and IP3 receptors
• C-terminal Coiled-Coil (CC) domain: Enables Homer multimerization

HOMER Isoforms

• HOMER3a: Full-length form, predominant in brain
• HOMER3b: Shorter variant with different expression pattern

Normal Neuronal Function

Synaptic Organization

HOMER3 is a core component of the postsynaptic density:

• mGluR Anchoring: Binds to group I mGluRs (mGluR1/5), positioning them at synaptic sites
• IP3 Receptor Linking: Connects mGluR signaling to calcium release from intracellular stores
• PSD Protein Interactions: Associates with PSD-95, Shank, and other scaffold proteins

Synaptic Plasticity

• Long-term Depression (LTD): Critical for mGluR-dependent LTD
• Calcium Signaling: Modulates intracellular calcium dynamics
• Actin Cytoskeleton: Links signaling to actin remodeling at synapses

Dendritic Spines

• Spine Formation: Promotes dendritic spine development
• Spine Maintenance: Stabilizes spine structure
• Synaptic Transmission: Regulates excitatory neurotransmission

Expression Pattern

HOMER3 is primarily expressed in the brain:

• Cerebral cortex (layers II-VI, pyramidal neurons)
• Hippocampus (CA1-CA3 pyramidal cells, dentate gyrus)
• Cerebellum (Purkinje cells)
• Striatum (medium spiny neurons)
• Olfactory bulb

Disease Associations

Alzheimer's Disease

• Synaptic Loss: HOMER3 downregulation contributes to synaptic dysfunction
• mGluR Signaling: Altered mGluR5 signaling in AD models
• Cognitive Decline: Linked to memory deficits

Schizophrenia

• Genetic Associations: HOMER3 variants associated with risk
• Synaptic Dysfunction: Altered expression in postmortem brain
• glutamate Hypothesis: Links to glutamatergic dysfunction

Autism Spectrum Disorders

• Synaptic Protein Interactions: Affected in some ASD cases
• Synaptic Plasticity: May contribute to circuit abnormalities

Epilepsy

• Seizure Activity: HOMER3 expression altered in epileptic brain
• Network Excitability: Modulates neuronal excitability

Signaling Pathways

HOMER3 integrates multiple signaling pathways:

• mGluR1/5 Signaling: Downstream of group I metabotropic glutamate receptors
• PI3K/Akt Pathway: Cell survival signaling
• MAPK/ERK Pathway: Synaptic plasticity and gene expression
• Calcium Signaling: IP3 receptor-mediated calcium release

Interaction Network

HOMER3 interacts with:

Research Highlights

• Homer1 knockout mice show impaired mGluR-dependent LTD
• Overexpression of HOMER3 enhances synaptic stability
• Viral delivery of HOMER vectors improves synaptic function in models

See Also

• [Homer1 Gene](/genes/homer1)
• [Homer2 Gene](/genes/homer2)
• [Synaptic Plasticity Pathway](/mechanisms/synaptic-plasticity-pathway)
• [mGluR Signaling](/mechanisms/mglur-signaling)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Schizophrenia](/diseases/schizophrenia)
• [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction-pathway)

External Links

• [NCBI Gene: HOMER3](https://www.ncbi.nlm.nih.gov/gene/84524)
• [UniProt: Q9NKUC6](https://www.uniprot.org/uniprot/Q9NKUC6)
• [GeneCards: HOMER3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=HOMER3)

References