Complement C1q Subunit A Protein

Complement C1q Subunit A Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Complement C1q Subunit A Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Complement C1q Subunit A</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[C1QA](/proteins/c1qa-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P02787](https://www.uniprot.org/uniprot/P02787)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>26 kDa (subunit), 460 kDa (complex)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Secreted, plasma membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>C1q family</td>
</tr>
<tr>
<td class="label">Drug/Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Anti-C1q antibodies</td>
<td>C1q</td>
</tr>
<tr>
<td class="label">C1s inhibitors</td>
<td>C1s</td>
</tr>
<tr>
<td class="label">CR3 antagonists</td>
<td>CD11b/CD18</td>
</tr>
<tr>
<td class="label">C3 inhibitors</td>
<td>C3</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/als" style="color:#ef9a9a">ALS</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 Connecti

Complement C1q Subunit A Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Complement C1q Subunit A Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Complement C1q Subunit A</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[C1QA](/proteins/c1qa-protein)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[P02787](https://www.uniprot.org/uniprot/P02787)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>26 kDa (subunit), 460 kDa (complex)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Secreted, plasma membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>C1q family</td>
</tr>
<tr>
<td class="label">Drug/Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Anti-C1q antibodies</td>
<td>C1q</td>
</tr>
<tr>
<td class="label">C1s inhibitors</td>
<td>C1s</td>
</tr>
<tr>
<td class="label">CR3 antagonists</td>
<td>CD11b/CD18</td>
</tr>
<tr>
<td class="label">C3 inhibitors</td>
<td>C3</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/als" style="color:#ef9a9a">ALS</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">1048 edges</a></td>
</tr>
</table>

Complement C1Q Subunit A 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.

C1q is the initiating molecule of the classical complement pathway and plays a critical role in synaptic pruning, neuroinflammation, and neurodegeneration. The C1q complex consists of six copies each of three subunits (A, B, and C), and C1q subunit A is essential for its function. [@hong2016]

Overview

C1q subunit A is a component of the C1 complex that initiates the classical complement cascade. C1q is expressed in the brain by microglia and neurons and plays important roles in synaptic pruning, phagocytosis, and neuroinflammation. It is emerging as a therapeutic target for neurodegenerative diseases. [@thielens2019]

This protein is involved in: [@bialas2020]

• Complement activation: Initiates classical pathway
• Synaptic pruning: Mediates synapse elimination
• Phagocytosis: Promotes microglial clearance
• Disease associations: Alzheimer's disease, ALS, synaptic loss

Protein Overview

Structure

The C1q molecule has a unique structural organization:

• Globular Heads (gC1q): Six globular domains at the C-terminus that bind to targets
• Stalk Regions: Collagen-like stems that trimerize
• N-terminal Cysteine Knot: Stabilizes the complex
• Glycosylation: N-linked glycans on the globular domains
• Quaternary Structure: Hexamer of A-B-C heterotrimers (18 polypeptide chains total)

Normal Function

C1q mediates complement activation and immune surveillance:

In the brain, C1q is produced by microglia and [astrocytes](/entities/astrocytes) and plays important roles in development and homeostasis.

Role in Disease

Alzheimer's Disease

C1q contributes to AD through multiple mechanisms:

• Synaptic Loss: Excessive pruning of synapses via complement activation
• [Aβ](/proteins/amyloid-beta) Engagement: Binds to amyloid plaques, enhancing inflammation
• Microglial Activation: Opsonizes targets for microglial phagocytosis
• Synapse Elimination: C1q-tagged synapses are eliminated by microglia
• Genetic Associations: C1Q polymorphisms linked to AD risk

Parkinson's Disease

In PD, C1q:

• Mediates complement activation in the substantia nigra
• Contributes to dopaminergic neuron death
• May tag Lewy bodies for immune clearance
• Affects microglial phagocytosis of [α-synuclein](/proteins/alpha-synuclein)

Amyotrophic Lateral Sclerosis

C1q in ALS:

• Upregulated in motor [cortex](/brain-regions/cortex) and spinal cord
• Contributes to neuromuscular junction elimination
• May accelerate motor neuron degeneration
• Target of therapeutic antibodies (αC1q)

Multiple Sclerosis

C1q signaling:

• Mediates demyelination through complement activation
• Affects oligodendrocyte survival
• Being targeted by anti-C1q antibodies in clinical trials

Molecular Mechanisms

Complement Cascade

C1q initiates the classical pathway:

• Binding to C1r/C1s protease complex → C1s activation
• C1s cleaves C4 and C2 → C4b2a (C3 convertase)
• C3 convertase cleaves C3 → C3b opsonization
• C5 convertase leads to membrane attack complex

Synaptic Pruning

Developmental and disease-associated pruning:

• C1q tags synapses for elimination
• C3b acts as opsonin for microglia
• CR3 (CD11b/CD18) receptor mediates phagocytosis
• Requires neuronal eat-me signals (e.g., phosphatidylserine exposure)

Therapeutic Targeting

Research Directions

Current investigation areas:

Key Publications

Background

The study of Complement C1Q Subunit A 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

• C1QA Gene
• [Proteins Index](/proteins)
• [Complement System](/entities/complement-system)
• [Synaptic Dysfunction](/mechanisms/synaptic-dysfunction)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Microglia](/cell-types/microglia)
• Synaptic Pruning