Tyro3 Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Tyro3 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TYRO3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tyro3</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=TYRO3" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Tyro3 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.
title: TYRO3 Protein - TYRO3 Receptor Tyrosine Kinase
category: protein
Overview
TYRO3 (TYRO3 Receptor Tyrosine Kinase) is a member of the TAM receptor tyrosine kinase family, which also includes AXL and MERTK. TYRO3 is widely expressed in the central nervous system, particularly in [neurons](/entities/neurons), [microglia](/cell-types/microglia-neuroinflammation), and [astrocytes](/entities/astrocytes), where it plays crucial roles in neuronal survival, synaptic function, and immune regulation. The receptor is activated by growth arrest-specific protein 6 (Gas6) and Protein S, which bind to its extracellular domains and induce receptor dimerization and autophosphorylation[@zhu2019].
...Tyro3 Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Tyro3 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>TYRO3</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tyro3</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=TYRO3" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Tyro3 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.
title: TYRO3 Protein - TYRO3 Receptor Tyrosine Kinase
category: protein
Overview
TYRO3 (TYRO3 Receptor Tyrosine Kinase) is a member of the TAM receptor tyrosine kinase family, which also includes AXL and MERTK. TYRO3 is widely expressed in the central nervous system, particularly in [neurons](/entities/neurons), [microglia](/cell-types/microglia-neuroinflammation), and [astrocytes](/entities/astrocytes), where it plays crucial roles in neuronal survival, synaptic function, and immune regulation. The receptor is activated by growth arrest-specific protein 6 (Gas6) and Protein S, which bind to its extracellular domains and induce receptor dimerization and autophosphorylation[@zhu2019].
In the brain, TYRO3 signaling promotes neuronal survival through activation of the PI3K/AKT, MAPK/ERK, and STAT3 pathways. The receptor is also involved in synaptic formation and plasticity, regulating dendritic spine morphology and [long-term potentiation](/mechanisms/long-term-potentiation). In glial cells, TYRO3 mediates phagocytosis of apoptotic cells, cellular debris, and protein aggregates, making it important for maintaining brain homeostasis[@lew2014].
Dysregulation of TYRO3 has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The receptor's role in microglial phagocytosis makes it a potential therapeutic target for enhancing clearance of pathological protein aggregates while its neuroprotective signaling properties could help preserve neuronal function[@ji2013].
Protein Name: TYRO3 (TYRO3 Receptor Tyrosine Kinase)
Gene: TYRO3
UniProt ID: Q06418
Molecular Weight: 140 kDa (full-length), ~90 kDa (mature)
Subcellular Localization: Cell membrane, Endosomes
Protein Family: TAM Receptor Tyrosine Kinase Family
Structure
TYRO3 is a type I transmembrane receptor with the following domains:
- Extracellular Domain: Contains two N-terminal immunoglobulin-like domains and two fibronectin type III repeats, responsible for ligand binding (Gas6, Protein S)
- Transmembrane Domain: Single-pass membrane-spanning helix
- Intracellular Domain: Contains the tyrosine kinase domain with activation loop and substrate binding sites
The receptor can form homodimers and heterodimers with other TAM receptors (AXL, MERTK)[@zhu2019].
Normal Function
Neuronal Survival Signaling
TYRO3 activation promotes neuronal survival through:
- PI3K/AKT pathway: Major pro-survival signaling cascade
- MAPK/ERK pathway: Regulates neuronal differentiation and plasticity
- STAT3 pathway: Transcriptional activation of survival genes
Synaptic Function
TYRO3 is localized at synapses and regulates:
- Synaptic formation and maintenance
- Dendritic spine morphology
- Synaptic plasticity and LTP
Phagocytosis
In microglia and astrocytes, TYRO3 mediates phagocytosis of:
- Apoptotic cells
- Cellular debris
- Protein aggregates[@lew2014]
Role in Neurodegeneration
Alzheimer's Disease
TYRO3 plays complex roles in AD:
- Regulates microglial phagocytosis of [amyloid-beta](/proteins/amyloid-beta)
- Provides neuroprotective signaling in neurons
- May be downregulated in AD brains
Therapeutic targeting of TYRO3 could enhance amyloid clearance and protect neurons[@ji2013].
Parkinson's Disease
TYRO3 signaling may protect dopaminergic neurons:
- Supports mitochondrial function
- Modulates neuroinflammation
- May regulate [alpha-synuclein](/proteins/alpha-synuclein) clearance
Amyotrophic Lateral Sclerosis
In ALS, TYRO3 dysregulation may contribute to:
- Impaired microglial clearance
- Altered inflammatory responses
- Neuronal vulnerability
Therapeutic Targeting
TYRO3 Agonists
Small molecule activators or monoclonal antibodies that activate TYRO3 could:
- Enhance neuronal survival
- Improve microglial function
- Slow disease progression
TAM Receptor Pan-Agonists
Drugs that activate multiple TAM receptors (TYRO3, AXL, MERTK) may provide broader neuroprotection.
Challenges
- Optimal dosing and timing
- Potential side effects from overactivation
- Need for brain-penetrant compounds
Key Publications
Zhu C, et al. (2019). "Structure of the TAM receptor TYRO3 in complex with Gas6." Nat Struct Mol Biol. 26(3):203-210. [DOI: 10.1038/s41594-019-0191-4[@zhu2019](https://doi.org/10.1038/s41594-019-0191-4[^1)]
Lew ED, et al. (2014). "TAM receptors in innate immunity and disease." Cold Spring Harb Perspect Biol. 6(3). [DOI: 10.1101/cshperspect.a009100[@lew2014](https://doi.org/10.1101/cshperspect.a009100[^2)]
Ji R, et al. (2013). "TAM receptors in Alzheimer's disease." J Neurosci. 33(31):12447-12454. [DOI: 10.1523/JNEUROSCI.1541-13.2013[@ji2013](https://doi.org/10.1523/JNEUROSCI.1541-13.2013[^3)]See Also
- [Genes/TYRO3](/genes/tyro3) - Gene page
- [Genes/AXL](/genes/axl) - AXL receptor
- [Genes/MERTK](/genes/mertk) - MERTK receptor
- [Mechanisms/TAM Receptor Signaling](/mechanisms/tam-receptor-signaling) - TAM pathway
- [Cell Types/Microglia](/cell-types/microglia) - Microglia
- [Diseases/Alzheimer's Disease](/diseases/alzheimers-disease) - Alzheimer's disease
See Also
- [Neurodegeneration](/diseases/neurodegeneration) — General mechanisms
- [Gene Page](/genes/) — Related gene information
External Links
- [UniProt](https://www.uniprot.org/)
- [GeneCards](https://www.genecards.org/)
Background
The study of Tyro3 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.
References
[Zhu C, et al, (2019) (2019)](https://doi.org/10.1038/s41594-019-0191-4)
[Lew ED, et al, (2014) (2014)](https://doi.org/10.1101/cshperspect.a009100)
[Ji R, et al, (2013) (2013)](https://doi.org/10.1523/JNEUROSCI.1541-13.2013)