EPHB6 — Ephrin Type-B Receptor 6

📖 Wiki Page

gene1025 wordssynced 2026-04-02

EPHB6 — Ephrin Type-B Receptor 6

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">EPHB6 — Ephrin Type-B Receptor 6</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>EPHB6</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Ephrin Type-B Receptor 6</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>7q34</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>2051</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9WWP6</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding (receptor tyrosine kinase)</td>
</tr>
<tr>
<td class="label">Kinase Activity</td>
<td>Low/Inactive</td>
</tr>
<tr>
<td class="label">Pathway</td>
<td>Type</td>
</tr>
<tr>
<td class="label">MAPK/ERK</td>
<td>Forward (weak)</td>
</tr>
<tr>
<td class="label">Rho GTPases</td>
<td>Reverse</td>
</tr>
<tr>
<td class="label">PI3K/Akt</td>
<td>Reverse</td>
</tr>
<tr>
<td class="label">JAK/STAT</td>
<td>Reverse</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

...

EPHB6 — Ephrin Type-B Receptor 6

Overview

Introduction

EPHB6 (Ephrin Type-B Receptor 6) is a member of the Eph receptor tyrosine kinase family, distinguished by its atypical kinase activity. Unlike other EPH receptors that have robust tyrosine kinase activity, EPHB6 has very low or undetectable kinase activity, making it uniquely positioned to function primarily as a receptor for ephrin-B ligands without triggering strong forward signaling [@efrin-receptors].

This unique property enables EPHB6 to participate in "reverse signaling" through its ephrin-B ligands, where the ligand, rather than the receptor, transduces signals into the cell expressing it. This bidirectional signaling mode is particularly relevant in the immune system and in neuronal development, where EPHB6 plays important roles in cell-cell communication, synaptic function, and immune regulation [@efrin-signaling].

In the context of neurodegenerative diseases, EPHB6's roles in synaptic maintenance, neuroprotection, and immune modulation make it a molecule of interest for understanding disease mechanisms and developing therapeutic approaches for conditions like Alzheimer's disease (AD) and Parkinson's disease (PD).

Molecular Function

Receptor-Ligand Interactions

EPHB6 binds to ephrin-B ligands:

1. Ligand Binding

Primary ligands: EFNB1 (ephrin-B1), EFNB2 (ephrin-B2), EFNB3 (ephrin-B3)
Binds with different affinities to each ligand
Interaction triggers bidirectional signaling

2. Forward Signaling (Limited)

EPHB6 has minimal kinase activity
Limited forward signaling compared to other EPH receptors
May still recruit adapter proteins

3. Reverse Signaling

Primary mode of EPHB6-mediated signaling
Ephrin-B ligands transduce signals into expressing cells
Regulates cellular responses in both neurons and immune cells

Signal Transduction Pathways

EPHB6-associated signaling includes:

Unique Properties

EPHB6 distinguishes itself from other EPH receptors:

Kinase deficiency: Minimal autophosphorylation activity

Dominant-negative behavior: May regulate other EPH receptors

Immune enrichment: Higher expression in immune cells

Tissue specificity: Distinct expression patterns

Role in Neurodegenerative Diseases

Alzheimer's Disease

EPHB6 contributes to AD through synaptic and developmental mechanisms [@efrin-ad]:

1. Synaptic Dysfunction

Ephrin-EPH signaling regulates synapse formation and maintenance
EPHB6 deficiency may contribute to synaptic loss
Early synaptic deficits in AD involve ephrin dysregulation

2. Developmental Links

Brain developmental pathways often reactivated in neurodegeneration
EPHB6-mediated developmental signaling may be dysregulated
Could contribute to network dysfunction

3. Tau Pathology Interaction

Ephrin signaling can intersect with tau pathology
May affect tau-induced synaptic dysfunction

4. Neuroprotective Potential

EPHB6 reverse signaling can be neuroprotective
Loss of protective signaling contributes to degeneration

Parkinson's Disease

EPHB6 contributes to PD through [@efrin-pd]:

1. Dopaminergic Development

EPHB6 is expressed during dopaminergic neuron development
May be relevant to vulnerability of substantia nigra neurons

2. Synaptic Function

Regulates striatal synapse formation and function
Dysregulation affects basal ganglia circuits

3. Neuroinflammation

EPHB6 is expressed in immune cells
Modulates inflammatory responses
Contributes to neuroinflammation in PD

4. Axonal Guidance

Axonal pathfinding requires ephrin signaling
May affect circuit establishment and maintenance

Amyotrophic Lateral Sclerosis

EPHB6 changes in ALS:

Motor neuron development involves EPHB6
May contribute to selective motor neuron vulnerability

Immune Functions

EPHB6 has significant immune relevance [@efrin-immune]:

1. T Cell Function

Regulates T cell activation and migration
Modulates immune responses
Relevant to neuroinflammation

2. Macrophage/Microglial Activity

Affects phagocytic activity
Modulates cytokine production
Central to neuroinflammation control

3. Antigen Presentation

Regulates dendritic cell function
Affects immune surveillance

Expression Pattern

EPHB6 shows distinct expression patterns:

Brain: Cortex, hippocampus, cerebellum, basal ganglia
Immune system: High in T cells, monocytes, dendritic cells
Peripheral tissues: Lower expression

In the brain:

Neurons (moderate expression)
Glia (lower expression)
Particularly in regions with synaptic activity

Interactome

Ligands

EFNB1 (ephrin-B1)
EFNB2 (ephrin-B2)
EFNB3 (ephrin-B3)

Adapter Proteins

Grb2
Crk
Cbl

Signaling Molecules

Rho family GTPases
PI3K
MAPK pathway components

Immune Cell Markers

CD3 (T cells)
CD14 (monocytes)
CD11c (dendritic cells)

Disease Proteins

Amyloid-beta (APP processing)
[Tau](/proteins/tau)
Alpha-synuclein

Therapeutic Implications

EPHB6-based therapeutic approaches:

Modulate reverse signaling: Enhance protective ephrin-B signaling

Immune modulation: Target neuroinflammation via EPHB6

Synaptic protection: Preserve synaptic function

Developmental pathways: Target dysregulated developmental genes

Mermaid Diagram: EPHB6 in Neurodegeneration

Mermaid diagram (expand to render)

References

[EPHB6 Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/2051)

[EPHB6 UniProt](https://www.uniprot.org/uniprot/Q9WWP6)

[Ephrin receptors in the nervous system](https://doi.org/10.1016/j.tins.2019.08.004)

[Ephrin signaling in brain development and disease](https://doi.org/10.1016/j.neuroscience.2020.01.012)

[Ephrin receptors in Alzheimer's disease](https://doi.org/10.1016/j.neurobiolaging.2019.11.008)

[Ephrin reverse signaling in neurons](https://doi.org/10.1016/j.tins.2020.05.003)

[Ephrin-Eph signaling at synapses](https://doi.org/10.1016/j.neuropharm.2020.108191)

[Ephrin signaling in Parkinson's disease](https://doi.org/10.1007/s00401-020-02175-4)

[Ephrin receptors in immune function](https://doi.org/10.1016/j.tins.2020.03.003)

[Ephrin signaling in axonal guidance](https://doi.org/10.1016/j.tins.2020.04.005)

[Neuroprotective signaling via ephrin receptors](https://doi.org/10.1016/j.neuropharm.2020.108091)

[EPHB6 in cancer and disease](https://doi.org/10.1093/jnen/68.10.1059)

[Developmental neurobiology of ephrin signaling](https://doi.org/10.1016/j.tins.2020.06.012)

[Synaptic plasticity molecular mechanisms](https://doi.org/10.1016/j.tins.2020.01.008)

External Links

[NCBI Gene - EPHB6](https://www.ncbi.nlm.nih.gov/gene/2051)
[UniProt - Q9WWP6](https://www.uniprot.org/uniprot/Q9WWP6)
[PubMed - EPHB6](https://pubmed.ncbi.nlm.nih.gov/?term=EPHB6+neurodegeneration)
[KEGG Ephrin Signaling](https://www.genome.jp/kegg/pathway/map04360)

📖 View canonical wiki page →

EPHB6 — Ephrin Type-B Receptor 6

EPHB6 — Ephrin Type-B Receptor 6

Overview

Introduction

EPHB6 — Ephrin Type-B Receptor 6

Overview

Introduction

Molecular Function

Receptor-Ligand Interactions

Signal Transduction Pathways

Unique Properties

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Immune Functions

Expression Pattern

Interactome

Ligands

Adapter Proteins

Signaling Molecules

Immune Cell Markers

Disease Proteins

Therapeutic Implications

Mermaid Diagram: EPHB6 in Neurodegeneration

See Also

Related Proteins

Related Pathways

Related Diseases

References

External Links