EPHA1 Protein
Introduction
Epha1 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.
EPHA1 (EPH Receptor A1) is a member of the ephrin receptor family of receptor tyrosine kinases. GWAS have identified EPHA1 as a genetic risk factor for late-onset Alzheimer's disease (LOAD), with protective variants reducing AD risk. EPHA1 is involved in cell migration, synaptic plasticity, and may play roles in neuroinflammation. [@holmans2013]
Overview
EPHA1 (EPH Receptor A1) is a member of the ephrin receptor family of receptor tyrosine kinases, one of the largest families of receptor tyrosine kinases in the human genome. The EPHA subfamily includes eight receptors (EPHA1-8) that bind to five ephrin-A ligands (EFNA1-5). EPHA1 was first identified as a cell surface antigen (EphA1) and has been studied primarily in the context of cancer. However, GWAS have identified EPHA1 as a genetic risk factor for late-onset Alzheimer's disease (LOAD), with protective variants reducing AD risk. EPHA1 is widely expressed in the brain, particularly in [neurons](/entities/neurons) and [astrocytes](/entities/astrocytes), where it regulates synaptic plasticity, cell migration, and neuroinflammatory responses. [@karch2012]
...EPHA1 Protein
Introduction
Epha1 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.
EPHA1 (EPH Receptor A1) is a member of the ephrin receptor family of receptor tyrosine kinases. GWAS have identified EPHA1 as a genetic risk factor for late-onset Alzheimer's disease (LOAD), with protective variants reducing AD risk. EPHA1 is involved in cell migration, synaptic plasticity, and may play roles in neuroinflammation. [@holmans2013]
Overview
EPHA1 (EPH Receptor A1) is a member of the ephrin receptor family of receptor tyrosine kinases, one of the largest families of receptor tyrosine kinases in the human genome. The EPHA subfamily includes eight receptors (EPHA1-8) that bind to five ephrin-A ligands (EFNA1-5). EPHA1 was first identified as a cell surface antigen (EphA1) and has been studied primarily in the context of cancer. However, GWAS have identified EPHA1 as a genetic risk factor for late-onset Alzheimer's disease (LOAD), with protective variants reducing AD risk. EPHA1 is widely expressed in the brain, particularly in [neurons](/entities/neurons) and [astrocytes](/entities/astrocytes), where it regulates synaptic plasticity, cell migration, and neuroinflammatory responses. [@karch2012]
Infobox
<div class="infobox infobox-protein"> [@cheng2015]
<div class="infobox-header">EPHA1 Protein</div> [@ma2017]
<div class="infobox-row"><strong>Protein Name:</strong> EPH Receptor A1</div> [@liu2019]
<div class="infobox-row"><strong>Gene:</strong> [EPHA1](/Genes/EPHA1)</div> [@shi2020]
<div class="infobox-row"><strong>UniProt ID:</strong> [P21709](https://www.uniprot.org/uniprot/P21709)</div> [@xu2021]
<div class="infobox-row"><strong>PDB ID:</strong> 3C8X</div>
<div class="infobox-row"><strong>Molecular Weight:</strong> 110 kDa</div>
<div class="infobox-row"><strong>Subcellular Localization:</strong> Plasma Membrane</div>
<div class="infobox-row"><strong>Protein Family:</strong> Ephrin receptor family</div>
</div>
Structure
EPHA1 is a receptor tyrosine kinase with an extracellular domain containing a ligand-binding domain, an EGF-like domain, and two fibronectin type III repeats. The cytoplasmic domain contains the tyrosine kinase domain and a sterile alpha motif (SAM). EPHA1 binds ephrin-A ligands (EFNA1-5) on adjacent cells, triggering bidirectional signaling.
Normal Function
EPHA1 (EPH Receptor A1) is a member of the ephrin receptor family of receptor tyrosine kinases. GWAS have identified EPHA1 as a genetic risk factor for late-onset Alzheimer's disease (LOAD), with protective variants reducing AD risk. EPHA1 is involved in cell migration, synaptic plasticity, and may play roles in neuroinflammation.
Role in Disease
In Alzheimer's disease, EPHA1 variants may influence neuroinflammation and synaptic plasticity. The protective variants reduce AD risk, possibly by modulating EPHA1 signaling in immune cells and neurons. EPHA1 is expressed in neurons and astrocytes.
Therapeutic Targeting
No EPHA1-targeted therapies exist for Alzheimer's disease. The development of EPHA1 modulators could provide new therapeutic approaches for AD treatment.
See Also
- [EPHA1 Gene](/genes/epha1)
- [Alzheimer's Disease](/diseases/alzheimers-disease)|Alzheimer's Disease]
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
- [Neurons](/cell-types/neurons)
- [Astrocytes](/cell-types/astrocytes)
External Links
- [EPHA1 UniProt Entry](https://www.uniprot.org/uniprot/P21709)
- [EPHA1 Gene Database (NCBI)](https://www.ncbi.nlm.nih.gov/gene/2041)
- [Alzheimer's Disease Genetics Consortium](https://www.niagads.org/)
Background
The study of Epha1 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
[Lambert JC, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/24162737/)
[Holmans P, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23851625/)
[Karch CM, et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22286218/)
[Cheng Y, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26228350/)
[Ma J, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28414137/)
[Liu G, et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31119472/)
[Shi L, et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32791952/)
[Xu J, et al, (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33301045/)