MERTK Protein - MER Tyrosine Kinase
Introduction
<table class="infobox infobox-protein">
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<th class="infobox-header" colspan="2">MERTK Protein - MER Tyrosine Kinase</th>
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<td class="label">Symbol</td>
<td><strong>MERTK</strong></td>
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<td class="label">Full Name</td>
<td>MERTK - MER Tyrosine Kinase</td>
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<td class="label">Type</td>
<td>Protein</td>
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<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=MERTK" target="_blank">Search UniProt</a></td>
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<td class="label">Associated Diseases</td>
<td><a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/hepatitis" style="color:#ef9a9a">Hepatitis</a></td>
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<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">60 edges</a></td>
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Mertk Protein Mer Tyrosine Kinase 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: MERTK Protein - MER Tyrosine Kinase
category: protein
Overview
...MERTK Protein - MER Tyrosine Kinase
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">MERTK Protein - MER Tyrosine Kinase</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>MERTK</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>MERTK - MER Tyrosine Kinase</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=MERTK" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cardiac" style="color:#ef9a9a">Cardiac</a>, <a href="/wiki/diabetes" style="color:#ef9a9a">Diabetes</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/hepatitis" style="color:#ef9a9a">Hepatitis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">60 edges</a></td>
</tr>
</table>
Mertk Protein Mer Tyrosine Kinase 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: MERTK Protein - MER Tyrosine Kinase
category: protein
Overview
MERTK (MER Tyrosine Kinase) is a protein encoded by a gene located on chromosome 2q13. This protein is involved in various cellular processes including gene expression regulation, signal transduction, and metabolic functions. MERTK plays important roles in neuronal function and is implicated in neurodegenerative diseases.
Protein Name: MERTK (MER Proto-Oncogene, Tyrosine Kinase)
Gene: MERTK
UniProt ID: Q12866
Molecular Weight: 110 kDa (full-length)
Subcellular Localization: Cell membrane, Phagolysosomes
Protein Family: TAM Receptor Tyrosine Kinase Family
Structure
MERTK is a type I transmembrane receptor with characteristic TAM family architecture:
- Extracellular Domain:
- Two N-terminal immunoglobulin-like (Ig-like) domains
- Two fibronectin type III (FNIII) repeats
- Binds Gas6 and Protein S with different affinities
- Transmembrane Domain: Single-pass membrane-spanning helix
- Intracellular Domain:
- Tyrosine kinase domain
- Multiple tyrosine phosphorylation sites
- Mediates downstream signaling
The receptor can form homodimers upon ligand binding[@graham2014].
Normal Function
Phagocytosis
MERTK is a key phagocytic receptor:
- Recognizes phosphatidylserine on apoptotic cells
- Mediates engulfment of dead cells
- Essential for tissue homeostasis
- Critical for photoreceptor outer segment phagocytosis in retina
Cell Survival Signaling
MERTK promotes cell survival through:
- PI3K/AKT pathway: Major pro-survival cascade
- MAPK/ERK pathway: Cell growth and differentiation
- STAT3 pathway: Transcriptional activation
Immune Regulation
MERTK modulates immune responses:
- Regulates macrophage activation
- Controls inflammatory cytokine production
- Maintains immune tolerance
Role in Neurodegeneration
Alzheimer's Disease
MERTK plays complex roles in AD:
- Amyloid Clearance: Mediates microglial phagocytosis of [Aβ](/proteins/amyloid-beta)
- Synaptic Pruning: Involved in developmental and pathological synapse elimination
- Neuroinflammation: Modulates microglial activation state
Dysregulated MERTK signaling may contribute to AD progression[@chung2018].
Retinitis Pigmentosa
MERTK mutations cause autosomal recessive retinitis pigmentosa:
- Impaired phagocytosis of photoreceptor outer segments
- Progressive photoreceptor degeneration
- Night blindness progressing to complete blindness
Gene therapy approaches are in development[@ghazi2018].
Parkinson's Disease
In PD, MERTK may:
- Modulate microglial activation
- Affect dopaminergic neuron survival
- Influence [α-synuclein](/proteins/alpha-synuclein) clearance
Amyotrophic Lateral Sclerosis
MERTK dysregulation in ALS:
- Altered microglial phagocytosis
- Dysregulated immune responses
Therapeutic Targeting
MERTK Modulators
Small molecules that activate or inhibit MERTK could treat various conditions:
Agonists could:
- Enhance amyloid clearance in AD
- Promote phagocytosis of protein aggregates
- Provide neuroprotective signaling
Inhibitors could:
- Reduce excessive phagocytosis
- Modulate neuroinflammation
Gene Therapy
AAV-mediated MERTK gene therapy for RP has shown promising results in clinical trials.
Key Publications
Graham DK, et al. (2014). "The TAM family: phosphatidylserine-sensing receptor tyrosine kinases." Cytokine Growth Factor Rev. 25(2):175-190. [DOI:10.1016/j.cytogfr.2014.03.003[@graham2014](https://doi.org/10.1016/j.cytogfr.2014.03.003[^1)]
Chung WS, et al. (2018). "[Microglia](/entities/microglia) are requisite for the enhanced therapeutic efficacy of neural progenitor cells in adult mouse brain." Nat Neurosci. 21(4):543-553. [DOI:10.1038/s41593-018-0093-4[@chung2018](https://doi.org/10.1038/s41593-018-0093-4[^2)]
Ghazi NG, et al. (2018). "Treatment of MERTK-associated retinitis pigmentosa with AAV-vector gene therapy." Nat Med. 24(7):939-947. [DOI:10.1038/s41591-018-0097-2[@ghazi2018](https://doi.org/10.1038/s41591-018-0097-2[^3)]See Also
- [Genes/MERTK](/genes/mertk) - Gene page
- [Genes/TYRO3](/genes/tyro3) - TYRO3 receptor
- [Genes/AXL](/genes/axl) - AXL receptor
- [Mechanisms/TAM Receptor Signaling](/mechanisms/tam-receptor-signaling) - TAM pathway
- [Cell Types/Microglia](/cell-types/microglia) - [Microglia](/cell-types/microglia-neuroinflammation)
- [Diseases/Alzheimer's Disease](/diseases/alzheimers-disease) - Alzheimer's disease
Background
The study of Mertk Protein Mer Tyrosine Kinase 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.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
[Graham DK, et al, (2014) (2014)](https://doi.org/10.1016/j.cytogfr.2014.03.003)
[Chung WS, et al, (2018) (2018)](https://doi.org/10.1038/s41593-018-0093-4)
[Ghazi NG, et al, (2018) (2018)](https://doi.org/10.1038/s41591-018-0097-2)