HOMER2 Protein

HOMER2 Protein — Homer Scaffold Protein 2

Introduction

Homer2 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.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">HOMER2 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Homer Scaffold Protein 2</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>HOMER2</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NSC5](https://www.uniprot.org/uniprot/Q9NSC5)</td></tr>
<tr><td><strong>Function</strong></td><td>Postsynaptic scaffolding protein organizing glutamate receptor signaling complexes</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~184 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Postsynaptic density, [dendritic spines](/mechanisms/dendritic-spines)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Homer family of scaffold proteins</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

HOMER2 Protein — Homer Scaffold Protein 2

Introduction

Homer2 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.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">HOMER2 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Homer Scaffold Protein 2</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>HOMER2</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NSC5](https://www.uniprot.org/uniprot/Q9NSC5)</td></tr>
<tr><td><strong>Function</strong></td><td>Postsynaptic scaffolding protein organizing glutamate receptor signaling complexes</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~184 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Postsynaptic density, [dendritic spines](/mechanisms/dendritic-spines)</td></tr>
<tr><td><strong>Protein Family</strong></td><td>Homer family of scaffold proteins</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

HOMER2 (Homer Scaffold Protein 2) is a postsynaptic density (PSD) scaffolding protein that organizes glutamatergic synapse structure and function[@tu1999]. Homer proteins are characterized by an N-terminal EVH1 (Enabled/Vasp Homology 1) domain that binds to proline-rich motifs in target proteins and a C-terminal coiled-coil domain that mediates multimerization[@naisbitt1999]. HOMER2 plays critical roles in synaptic plasticity, calcium homeostasis, and group I metabotropic glutamate receptor (mGluR1/5) signaling. Dysregulation of HOMER2 has been implicated in Alzheimer's disease, schizophrenia, and other neuropsychiatric disorders[@sun2018][@liu2022].

Molecular Mechanisms

Domain Structure and Binding Partners

HOMER2 contains several functional domains[@tu1999][@naisbitt1999]:

• EVH1 Domain (N-terminal): Binds to proline-rich motifs (PPXXF) in target proteins including:
• Group I mGluRs (mGluR1, mGluR5)
• Shank proteins
• TRPV1 channels
• IRSp53/MIM
• Synaptic scaffolding proteins
• Coiled-Coil Domain (C-terminal): Mediates Homer-Homer multimerization, forming a lattice-like scaffold network
• Ligand-Binding Domain: Involved in interactions with other synaptic proteins

Synaptic Scaffold Function

HOMER2 organizes the postsynaptic density through multivalent interactions[@naisbitt1999]:

Synaptic Plasticity

HOMER2 is crucial for activity-dependent synaptic plasticity[@sun2018]:

• Long-Term Depression (LTD): mGluR5-HOMER2 signaling is essential for mGluR-LTD
• [Long-Term Potentiation](/mechanisms/long-term-potentiation) (LTP): HOMER2 affects [NMDA receptor](/entities/nmda-receptor) function indirectly through mGluR interactions
• Homeostatic Plasticity: HOMER2 levels adjust in response to chronic activity changes

Role in Neurodegeneration

Alzheimer's Disease

HOMER2 dysregulation contributes to AD pathogenesis through multiple mechanisms[@sun2018][@liu2022]:

Schizophrenia and Bipolar Disorder

HOMER2 is a risk gene for schizophrenia[@schizophrenia2014]:

• GWAS have identified HOMER2 variants associated with schizophrenia risk
• HOMER2 expression is altered in prefrontal [cortex](/brain-regions/cortex) of schizophrenia patients
• Dysregulated Homer2 affects glutamatergic synapse function relevant to psychotic disorders

Epilepsy

HOMER2 plays a role in seizure susceptibility[@tappe2006]:

• Homer2 knockout mice show increased seizure susceptibility
• HOMER2 regulates mGluR5 signaling that controls neuronal excitability
• Altered HOMER2 may contribute to hyperexcitability in epileptic tissue

Therapeutic Implications

HOMER2 is a potential therapeutic target[@liu2022][@tappe2006]:

Pathway Interactions

HOMER2 integrates synaptic signaling pathways:

Key Research Findings

• HOMER2 expression is significantly reduced in prefrontal cortex and [hippocampus](/brain-regions/hippocampus) of AD patients[@sun2018]
• Homer2 knockout mice show deficits in mGluR-LTD and impaired spatial memory[@sun2018]
• Genetic variants in HOMER2 are associated with schizophrenia risk in GWAS[@schizophrenia2014]
• HOMER2 regulates Aβ-induced synaptic dysfunction through mGluR5 signaling[@liu2022]
• Homer2/cain (a negative regulator) balance controls synaptic structure and function[@naisbitt1999]

Background

The study of Homer2 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.

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

See Also

• [genes/homer2](/content/genes)
• [mechanisms/glutamatergic-signaling](/content/mechanisms)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Synaptic Plasticity](/therapeutics/section-195-synaptic-plasticity-network-modulation-cbs-psp)

External Links

• [UniProt: Q9NSC5](https://www.uniprot.org/uniprot/Q9NSC5)
• [NCBI Gene: HOMER2](https://www.ncbi.nlm.nih.gov/gene/9455)
• [RCSB PDB: HOMER2 structure](https://www.rcsb.org/)

References