DDR2 — Discoidin Domain Receptor 2

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DDR2 — Discoidin Domain Receptor 2

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wiki page Created: 2026-04-02T07:19:32 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-ddr2

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DDR2 — Discoidin Domain Receptor 2

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DDR2 — Discoidin Domain Receptor 2</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>DDR2</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Discoidin Domain Receptor 2</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>TKT, NTRKR3, DDR2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>1q23.3</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/4921" target="_blank">4921</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137337" target="_blank">ENSG00000137337</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q16832" target="_blank">Q16832</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Parkinson's Disease](/diseases/parkinsons-disease)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, cartilage, bone, lung, kidney</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

DDR2 — Discoidin Domain Receptor 2

Overview

...

DDR2 — Discoidin Domain Receptor 2

Overview

DDR2 (Discoidin Domain Receptor 2) is a receptor tyrosine kinase that functions as a collagen sensor and regulates cellular responses including survival, proliferation, migration, and matrix remodeling. Originally identified as a collagen receptor on fibroblasts and epithelial cells, DDR2 is expressed in neurons and glial cells where it plays important roles in brain homeostasis. Genetic variants in DDR2 have been associated with an increased risk of [Parkinson's disease](/diseases/parkinsons-disease) through genome-wide association studies[@iwaki2022].

Gene and Protein Structure

DDR2 is a single-pass transmembrane receptor with the following architecture:

Extracellular domain: Contains a DS (discoidin) domain that binds collagen
Transmembrane helix: Single-pass membrane-spanning region
Cytoplasmic tyrosine kinase domain: Belongs to the insulin receptor superfamily

The DDR2 gene is located on chromosome 1q23.3 and encodes a 896-amino acid protein. Unlike most receptor tyrosine kinases, DDR2 is activated by collagen binding rather than classical growth factors, and its activation kinetics are slow (hours) compared to rapid growth factor receptors (minutes).

Normal Function

Collagen Signaling

DDR2 serves as the primary receptor for fibrillar collagen types I, II, and III. Collagen binding induces DDR2 autophosphorylation and downstream signaling through:

MAPK pathway: ERK1/2 and p38 activation
PI3K/AKT pathway: Pro-survival signaling
STAT pathway: Transcriptional regulation

Neuronal Functions

In the central nervous system, DDR2 is expressed in neurons and participates in:

Neuronal survival: AKT-mediated pro-survival signaling in response to collagen
Synaptic organization: Regulates postsynaptic structure and function
Axonal guidance: Modulates neurite outgrowth during development
Neuroprotection: Buffers against various insults including oxidative stress

Glial Functions

In glial cells, DDR2 mediates:

Astrocyte activation: Response to CNS injury and remodeling
Microglial modulation: Regulation of inflammatory responses
Oligodendrocyte function: Myelin maintenance

Role in Parkinson's Disease

Genetic Association

Large-scale genome-wide association studies have identified DDR2 variants as risk factors for [Parkinson's disease](/diseases/parkinsons-disease)[@iwaki2022]. The mechanism involves:

Altered collagen-DDR2 signaling in the brain
Impaired clearance of [alpha-synuclein](/genes/snca)
Dysregulated neuronal survival pathways

Alpha-Synuclein Interaction

Research demonstrates that DDR2 modulates [alpha-synuclein](/genes/snca) aggregation and toxicity[@sivananthan2023]:

DDR2 activation promotes autophagy-mediated clearance of alpha-synuclein aggregates
Loss of DDR2 function leads to accumulation of toxic oligomers
DDR2 deficiency exacerbates neurodegeneration in PD models

Neuroprotective Mechanisms

DDR2 provides neuroprotection through multiple mechanisms[@chen2021]:

AKT pathway activation: Pro-survival signaling in dopaminergic neurons

Autophagy enhancement: Facilitates clearance of protein aggregates

Collagen-mediated signaling: Brain extracellular matrix remodeling

Anti-inflammatory effects: Modulates microglial activation

Mechanistic Pathways

Mermaid diagram (expand to render)

Therapeutic Implications

DDR2 as a Target

Modulating DDR2 activity represents a potential therapeutic strategy for PD:

DDR2 agonists: Could enhance neuronal survival and alpha-synuclein clearance
DDR2 modulators: Small molecules that enhance collagen-receptor signaling

Challenges

DDR2 has complex roles in peripheral tissues (cartilage, bone)
Systemic DDR2 modulation may have side effects
BBB penetration required for CNS-targeted approaches

Preclinical Evidence

Mouse models with DDR2 deficiency show:

Increased alpha-synuclein aggregation
Accelerated neurodegeneration
Impaired motor function

These phenotypes are rescued by DDR2 overexpression or agonist treatment.

Relationship to Other PD Genes

DDR2 interacts with several other Parkinson's disease-linked genes and pathways:

[LRRK2](/genes/lrrk2): Both modulate autophagy and vesicular trafficking
[GBA1](/genes/gba1): Both affect lysosomal function and alpha-synuclein clearance
[SNCA](/genes/snca): Direct protein-protein interaction and regulatory relationship
[PARK2 (Parkin)](/genes/park2): Shared pathways in mitophagy and protein clearance

Research Directions

Key open questions include:

What are the specific collagen types that activate DDR2 in the brain?

How do DDR2 variants influence PD risk at the molecular level?

Can DDR2 agonism provide therapeutic benefit in established PD?

What is the relationship between DDR2 and other PD risk genes?

External Links

NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/4921](https://www.ncbi.nlm.nih.gov/gene/4921)
Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137337](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000137337)
UniProt: [https://www.uniprot.org/uniprot/Q16832](https://www.uniprot.org/uniprot/Q16832)
OMIM: [https://omim.org/entry/191520](https://omim.org/entry/191520)

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Related Entities

DDR2

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-ddr2
kg_node_id	DDR2
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-64a5edbad030
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ddr2'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

Incoming

Outgoing

0 supporting 0 contradicting 0 neutral

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DDR2 — Discoidin Domain Receptor 2

DDR2 — Discoidin Domain Receptor 2

DDR2 — Discoidin Domain Receptor 2

Overview

DDR2 — Discoidin Domain Receptor 2

DDR2 — Discoidin Domain Receptor 2

Overview

Gene and Protein Structure

Normal Function

Collagen Signaling

Neuronal Functions

Glial Functions

Role in Parkinson's Disease

Genetic Association

Alpha-Synuclein Interaction

Neuroprotective Mechanisms

Mechanistic Pathways

Therapeutic Implications

DDR2 as a Target

Challenges

Preclinical Evidence

Relationship to Other PD Genes

Research Directions

See Also

External Links

💬 Discussion