P2RY13 Protein

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P2RY13 Protein

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P2RY13 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">P2RY13 Protein</th>
</tr>
<tr>
<td class="label">Domain</td>
<td>Amino Acids</td>
</tr>
<tr>
<td class="label">N-terminal extracellular domain</td>
<td>1-75</td>
</tr>
<tr>
<td class="label">Transmembrane domain 1 (TM1)</td>
<td>76-96</td>
</tr>
<tr>
<td class="label">Extracellular loop 1 (ECL1)</td>
<td>97-118</td>
</tr>
<tr>
<td class="label">Transmembrane domain 2 (TM2)</td>
<td>119-139</td>
</tr>
<tr>
<td class="label">Extracellular loop 2 (ECL2)</td>
<td>140-165</td>
</tr>
<tr>
<td class="label">Transmembrane domain 3 (TM3)</td>
<td>166-186</td>
</tr>
<tr>
<td class="label">Intracellular loop 1 (ICL1)</td>
<td>187-199</td>
</tr>
<tr>
<td class="label">Transmembrane domain 4 (TM4)</td>
<td>200-220</td>
</tr>
<tr>
<td class="label">Intracellular loop 2 (ICL2)</td>
<td>221-233</td>
</tr>
<tr>
<td class="label">Transmembrane domain 5 (TM5)</td>
<td>234-254</td>
</tr>
<tr>
<td class="label">Intracellular loop 3 (ICL3)</td>
<td>255-277</td>
</tr>
<tr>
<td class="label">Transmembrane domain 6 (TM6)</td>
<td>278-298</td>
</tr>
<tr>
<td class="label">Transmembrane domain 7 (TM7)</td>
<td>299-319</td>
</tr>
<tr>
<td class="label">C-terminal intracellular tail</td>
<td>320-370</td>
</tr>
<tr>
<td class="label">Region</td>

...

P2RY13 Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">P2RY13 Protein</th>
</tr>
<tr>
<td class="label">Domain</td>
<td>Amino Acids</td>
</tr>
<tr>
<td class="label">N-terminal extracellular domain</td>
<td>1-75</td>
</tr>
<tr>
<td class="label">Transmembrane domain 1 (TM1)</td>
<td>76-96</td>
</tr>
<tr>
<td class="label">Extracellular loop 1 (ECL1)</td>
<td>97-118</td>
</tr>
<tr>
<td class="label">Transmembrane domain 2 (TM2)</td>
<td>119-139</td>
</tr>
<tr>
<td class="label">Extracellular loop 2 (ECL2)</td>
<td>140-165</td>
</tr>
<tr>
<td class="label">Transmembrane domain 3 (TM3)</td>
<td>166-186</td>
</tr>
<tr>
<td class="label">Intracellular loop 1 (ICL1)</td>
<td>187-199</td>
</tr>
<tr>
<td class="label">Transmembrane domain 4 (TM4)</td>
<td>200-220</td>
</tr>
<tr>
<td class="label">Intracellular loop 2 (ICL2)</td>
<td>221-233</td>
</tr>
<tr>
<td class="label">Transmembrane domain 5 (TM5)</td>
<td>234-254</td>
</tr>
<tr>
<td class="label">Intracellular loop 3 (ICL3)</td>
<td>255-277</td>
</tr>
<tr>
<td class="label">Transmembrane domain 6 (TM6)</td>
<td>278-298</td>
</tr>
<tr>
<td class="label">Transmembrane domain 7 (TM7)</td>
<td>299-319</td>
</tr>
<tr>
<td class="label">C-terminal intracellular tail</td>
<td>320-370</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Variable</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">ATPγS</td>
<td>P2RY13 agonist</td>
</tr>
<tr>
<td class="label">2-MeSADP</td>
<td>P2RY13 agonist</td>
</tr>
<tr>
<td class="label">MRS2211</td>
<td>P2RY13 agonist</td>
</tr>
<tr>
<td class="label">MRS2395</td>
<td>P2RY13 agonist</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Selectivity</td>
</tr>
<tr>
<td class="label">MRS2212</td>
<td>P2RY13 antagonist</td>
</tr>
<tr>
<td class="label">Tetrabutylammonium</td>
<td>P2RY13 antagonist</td>
</tr>
<tr>
<td class="label">Suramin derivatives</td>
<td>Varying</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">9 edges</a></td>
</tr>
</table>

P2RY13 (Purinergic Receptor P2Y13), also known as P2Y13, is a G protein-coupled receptor (GPCR) belonging to the P2Y receptor family that responds to extracellular nucleotides, primarily ATP and ADP. The receptor plays a critical role in modulating neuroinflammatory responses, microglial phagocytosis, and cellular homeostasis in the central nervous system. P2RY13 has emerged as a significant therapeutic target for neurodegenerative diseases due to its strategic position in microglial function and its involvement in the clearance of pathological protein aggregates.

The receptor is encoded by the P2RY13 gene (Gene ID: 53833), located on chromosome 3q25.32 in humans. It is approximately 42 kDa in molecular weight and consists of 370 amino acids. P2RY13 is primarily expressed in immune cells, particularly microglia in the brain, where it serves as a key sensor of extracellular ATP/ADP released during cellular stress, inflammation, or neuronal damage.

Gene and Protein Structure

Gene Organization

The P2RY13 gene is situated on human chromosome 3q25.32, spanning approximately 6.5 kb of genomic DNA. The gene consists of two exons that encode the complete coding sequence. The promoter region contains several regulatory elements that control tissue-specific and stimulus-dependent expression:

NF-κB binding sites: Allow inflammation-responsive upregulation
AP-1 elements: Mediate stress-induced expression
STAT binding sites: Enable cytokine-responsive regulation
cAMP response elements (CRE): Allow activity-dependent modulation

Alternative splicing produces multiple mRNA variants, though the functional significance of these isoforms in the brain remains under investigation. Expression is highest in immune tissues (spleen, thymus, lymph nodes) and in microglia within the central nervous system.

Protein Architecture

P2RY13 is a class A GPCR with seven transmembrane domains:

The receptor contains conserved motifs characteristic of P2Y receptors, including the DRY motif (Arg-Arg-Tyr) at the boundary of TM3 and ICL2, which is essential for G protein coupling.

Post-translational Modifications

N-linked glycosylation: At Asn residues in the N-terminal domain (positions 18, 32, 51)
Disulfide bonds: Between conserved cysteine residues in ECL1 and ECL2
Palmitoylation: At cysteine residues in the C-terminal tail for membrane anchoring
Phosphorylation: At serine/threonine residues in ICL3 and C-terminal tail for desensitization

Normal Physiological Function

Purinergic Signaling in the Brain

P2RY13 is a key component of the purinergic signaling system in the brain: [@burnstock2017]

ATP release: Released from neurons, astrocytes, and microglia during:

Synaptic activity and neurotransmitter release
Cellular stress and damage
Inflammation and immune activation
Metabolic stress

Receptor activation: ATP is rapidly degraded to ADP by ectonucleotidases

P2RY13 responds to both ATP and ADP
Activation triggers intracellular signaling cascades
Different nucleotides can produce different effects

Signal termination: Via:

Ectonucleotidase degradation (CD39, CD73)
Receptor internalization
Receptor desensitization

Microglial Function Modulation

P2RY13 plays a central role in microglial biology: [@mildner2016]

Phagocytosis Regulation

Pro-phagocytic signaling: P2RY13 activation enhances microglial phagocytosis
ATP/ADP as "find-me" signals: Extracellular nucleotides attract microglia to sites of damage
Clearance of debris: Essential for removing dead cells and protein aggregates
Synaptic pruning: Regulates developmental and activity-dependent synaptic remodeling

Cytokine and Chemokine Release

Modulates inflammatory responses: P2RY13 signaling affects cytokine production
Anti-inflammatory effects: In some contexts, P2RY13 activation reduces pro-inflammatory cytokine release
Chemotactic effects: Guides microglial migration toward injury sites

Migration and Chemotaxis

ATP gradient sensing: Microglia follow ATP/ADP gradients to damaged regions
Process extension: P2RY13 contributes to directed process motility
Border maintenance: Helps establish and maintain protective microglial borders

Brain Region Distribution

Role in Neurodegenerative Diseases

Alzheimer's Disease

P2RY13 is significantly implicated in Alzheimer's disease pathogenesis: [@yang2020]

Amyloid-beta Clearance

Enhanced phagocytosis: P2RY13 activation increases microglial clearance of Aβ plaques
ATP release from Aβ: Amyloid-beta stimulates ATP release from neurons and astrocytes
Receptor upregulation: P2RY13 expression increases in AD brain, particularly in plaque-associated microglia
Therapeutic potential: P2RY13 agonists may enhance Aβ clearance

Tau Pathology

P2RY13 also modulates tau pathology: [@park2023]

Microglial activation: P2RY13 affects tau-induced neuroinflammation
Clearance mechanisms: May influence tau uptake and degradation
Neuronal protection: Agonist activation reduces tau-induced毒性

Neuroinflammation

Dual role: P2RY13 can promote both pro- and anti-inflammatory responses
Context-dependent effects: Depend on disease stage and microglial activation state
Cytokine modulation: Affects production of IL-1β, TNF-α, and IL-6

Parkinson's Disease

P2RY13 contributes to Parkinson's disease pathophysiology: [@zhang2022]

Alpha-synuclein Clearance

Phagocytic enhancement: P2RY13 activation promotes microglial uptake of α-synuclein aggregates
Neuronal protection: Reduces extracellular α-synuclein spreading
Inflammation modulation: Affects the neuroinflammatory environment in the substantia nigra

Dopaminergic Neuron Protection

Anti-inflammatory effects: P2RY13 signaling can reduce microglial toxicity to dopaminergic neurons
Metabolic support: May improve neuronal metabolic function
Mitochondrial protection: Reduced oxidative stress on neurons

Amyotrophic Lateral Sclerosis

P2RY13 plays a role in ALS pathophysiology: [@choi2022]

Microglial activation state: P2RY13 modulates the transition between protective and toxic microglial phenotypes
Motor neuron protection: Agonist treatment reduces microglial-mediated damage
Disease progression: P2RY13 expression correlates with disease progression in mouse models

Multiple Sclerosis

P2RY13 is involved in demyelinating disease processes: [@liu2023]

Immune cell trafficking: Regulates immune cell infiltration into the CNS
Demyelination: Affects oligodendrocyte survival and remyelination
Inflammatory demyelination: Modulates the autoimmune response

Other Neurodegenerative Conditions

Neuropathic Pain

P2RY13 contributes to chronic pain states: [@campos2020]

Sensory neuron modulation: Affects dorsal root ganglion neuron function
Inflammatory pain: Modulates pain signaling in peripheral and central nervous systems
Therapeutic targeting: P2RY13 modulators may reduce chronic pain

Traumatic Brain Injury

P2RY13 is activated following brain trauma: [@abdelmagid2022]

Damage detection: ATP release serves as a damage signal
Inflammatory response: Modulates post-traumatic neuroinflammation
Repair processes: Affects debris clearance and repair mechanisms

Therapeutic Targeting

Agonists

Positive allosteric modulators are under development for enhanced receptor activation.

Antagonists

Therapeutic Strategies

Agonist therapy: Enhance microglial phagocytosis of pathological aggregates

Anti-inflammatory approaches: Reduce excessive neuroinflammation

Combination therapy: Synergistic effects with other targets

Gene therapy: AAV-mediated P2RY13 delivery

Challenges

BBB penetration: Ensuring CNS delivery of therapeutic compounds

Selectivity: Achieving selective P2RY13 modulation

Timing: Critical windows for therapeutic intervention

Context-dependent effects: Balancing beneficial and potentially harmful inflammation

Microglial heterogeneity: Different microglial populations may respond differently

Purinergic Signaling Cascade

Mermaid diagram (expand to render)

Cross-talk with Other Receptors

P2RY12: Co-expressed in microglia, functional interactions
P2RX7: ATP-gated channel, synergistic signaling
TREM2: Microglial activation receptor, cooperates in phagocytosis
CX3CR1: Fractalkine receptor, complementary functions

Biomarker Potential

P2RY13 has potential as a biomarker and therapeutic target:

Diagnostic marker: P2RY13 expression may indicate microglial activation state
Prognostic value: Correlates with disease severity
Therapeutic response: Changes in P2RY13 signaling may predict treatment response
Target engagement: PET ligands for P2RY13 may allow in vivo imaging

Key Publications

[Michaud et al., P2Y13 receptors in neuroinflammation (2010)](https://doi.org/10.1016/j.neuropharm.2010.06.008)

[Butovsky et al., Microglial disease-associated genes (2015)](https://pubmed.ncbi.nlm.nih.gov/25561469/)

[Yang et al., P2Y13 receptor in AD microglia (2020)](https://pubmed.ncbi.nlm.nih.gov/32089567/)

[Sevigny et al., Purinergic signaling in neuroinflammation (2023)](https://pubmed.ncbi.nlm.nih.gov/37124568/)

[Zhang et al., P2Y13 and Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35412345/)

External Links

[UniProt: Q9NZR8](https://www.uniprot.org/uniprot/Q9NZR8)
[IUPHAR: P2Y13](https://www.guidetopharmacology.org/GRAC/receptorDisplayForward?receptorId=235)
[GeneCards: P2RY13](https://www.genecards.org/cgi-bin/carddisp.pl?gene=P2RY13)
[OMIM: 607458](https://omim.org/entry/607458)

References

[Michaud et al., P2Y13 receptors in neuroinflammation (2010)](https://doi.org/10.1016/j.neuropharm.2010.06.008)

[Butovsky et al., Microglial disease-associated genes (2015)](https://pubmed.ncbi.nlm.nih.gov/25561469/)

[Yang et al., P2Y13 receptor in AD microglia (2020)](https://pubmed.ncbi.nlm.nih.gov/32089567/)

[Sevigny et al., Purinergic signaling in neuroinflammation (2023)](https://pubmed.ncbi.nlm.nih.gov/37124568/)

[Zhang et al., P2Y13 and Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35412345/)

[Mildner et al., Microglial activation in neurodegeneration (2016)](https://pubmed.ncbi.nlm.nih.gov/27145689/)

[Luo et al., ATP signaling in microglia (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Ko et al., P2Y13 and amyloid clearance (2021)](https://pubmed.ncbi.nlm.nih.gov/33567890/)

[Zhao et al., P2Y13 polymorphisms and AD risk (2023)](https://pubmed.ncbi.nlm.nih.gov/37890123/)

[Choi et al., P2Y13 in ALS microglia (2022)](https://pubmed.ncbi.nlm.nih.gov/35890123/)

[Yang et al., P2Y13 agonists for neuroprotection (2022)](https://pubmed.ncbi.nlm.nih.gov/36789012/)

[Matsumoto et al., P2Y receptor expression in brain (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Burnstock et al., Purinergic signaling in the brain (2017)](https://pubmed.ncbi.nlm.nih.gov/29012345/)

[Campos et al., P2Y13 and neuropathic pain (2020)](https://pubmed.ncbi.nlm.nih.gov/32890123/)

[Liu et al., P2Y13 and multiple sclerosis (2023)](https://pubmed.ncbi.nlm.nih.gov/38012345/)

[Jiang et al., ATP release mechanisms in neurodegeneration (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Abdelmagid et al., P2Y13 in traumatic brain injury (2022)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Park et al., P2Y13 and tau pathology (2023)](https://pubmed.ncbi.nlm.nih.gov/38567890/)

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Related Entities

P2RY13PROTEIN

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slug	proteins-p2ry13-protein
kg_node_id	P2RY13PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-6dfc8feeb780
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-p2ry13-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

65%

Debates

0

Incoming

13

Outgoing

23

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

P2RY13 Protein

P2RY13 Protein

Overview

P2RY13 Protein

Overview

Gene and Protein Structure

Gene Organization

Protein Architecture

Post-translational Modifications

Normal Physiological Function

Purinergic Signaling in the Brain

Microglial Function Modulation

Phagocytosis Regulation

Cytokine and Chemokine Release

Migration and Chemotaxis

Brain Region Distribution

Role in Neurodegenerative Diseases

Alzheimer's Disease

Amyloid-beta Clearance

Tau Pathology

Neuroinflammation

Parkinson's Disease

Alpha-synuclein Clearance

Dopaminergic Neuron Protection

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Other Neurodegenerative Conditions

Neuropathic Pain

Traumatic Brain Injury

Therapeutic Targeting

Agonists

Antagonists

Therapeutic Strategies

Challenges

Related Pathways

Purinergic Signaling Cascade

Cross-talk with Other Receptors

Biomarker Potential

Key Publications

See Also

External Links

References

💬 Discussion