ELOVL4 Protein — ELOVL Fatty Acid Elongase 4
Overview
Elovl4 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Elovl4 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. [@liu2013]
<div class="infobox infobox-protein"> [@connor2015]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">ELOVL4 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>ELOVL4 (ELOVL Fatty Acid Elongase 4)</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>ELOVL4</td></tr>
<tr><td><strong>Chromosome</strong></td><td>6q14.1</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9GZR7](https://www.uniprot.org/uniprot/Q9GZR7)</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>34.9 kDa</td></tr>
<tr><td><strong>Protein Length</strong></td><td>314 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Macular Degeneration</td></tr>
</table>
</div>
Protein Structure
...ELOVL4 Protein — ELOVL Fatty Acid Elongase 4
Overview
Elovl4 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Elovl4 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. [@liu2013]
<div class="infobox infobox-protein"> [@connor2015]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">ELOVL4 Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>ELOVL4 (ELOVL Fatty Acid Elongase 4)</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>ELOVL4</td></tr>
<tr><td><strong>Chromosome</strong></td><td>6q14.1</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9GZR7](https://www.uniprot.org/uniprot/Q9GZR7)</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>34.9 kDa</td></tr>
<tr><td><strong>Protein Length</strong></td><td>314 amino acids</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Macular Degeneration</td></tr>
</table>
</div>
Protein Structure
ELOVL4 is a transmembrane protein localized to the endoplasmic reticulum membrane. It contains multiple transmembrane domains and a conserved HXXHH motif characteristic of the ELOVL family of fatty acid elongases. The enzyme has a cytosolic N-terminus and luminal C-terminus. The active site contains the HXXHH histidine-rich motif that coordinates metal ion binding and catalyzes the condensation reaction. Structural studies reveal that ELOVL4 forms homooligomers in the ER membrane, which may regulate its enzymatic activity and substrate specificity.
Molecular Function
ELOVL4 catalyzes the first and rate-limiting step of very-long-chain fatty acid (VLCFA) synthesis - the condensation of malonyl-CoA with a long-chain acyl-CoA. Unlike other ELOVL family members, ELOVL4 specifically synthesizes C24-C36 saturated and polyunsaturated fatty acids. These VLCFAs are essential components of neuronal membranes, myelin sheaths, and photoreceptor outer segments.
The substrate specificity of ELOVL4 is unique among ELOVLs, preferring C20-C26 acyl-CoAs as substrates and producing VLCFAs that are incorporated into phospholipids, sphingolipids, and ceramides. This specificity is determined by the transmembrane domain architecture and the size of the substrate-binding pocket.
Role in Neurodegeneration
In Alzheimer's disease, ELOVL4 dysfunction leads to:
- Reduced VLC-PUFA levels in [neurons](/entities/neurons)
- Impaired synaptic membrane composition
- Increased susceptibility to [Aβ](/proteins/amyloid-beta) toxicity
- Defects in [autophagy](/entities/autophagy) and protein trafficking
Studies have shown that ELOVL4 expression is downregulated in Alzheimer's disease brains, particularly in the [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex). This reduction correlates with decreased levels of very-long-chain omega-3 fatty acids (VLC-PUFAs) in brain tissue. Animal models with ELOVL4 deficiency exhibit learning and memory deficits, further supporting its role in cognitive function.
In addition to Alzheimer's disease, ELOVL4 dysfunction has been implicated in age-related macular degeneration (AMD), where it plays a critical role in photoreceptor outer segment maintenance. The shared requirement for VLCFAs in both neuronal and retinal cells highlights the importance of ELOVL4 in specialized membrane compartments.
Therapeutic Targeting
Several therapeutic strategies targeting ELOVL4 are under investigation:
- VLC-PUFA supplementation: Providing products of ELOVL4 activity to bypass enzymatic deficits
- Gene therapy: AAV-mediated ELOVL4 delivery to restore enzymatic function
- Small molecule activators: Enhancing ELOVL4 enzymatic activity through allosteric modulation
- Protein-protein interaction inhibitors: Modulating ELOVL4 oligomerization to regulate activity
Key Publications
[15870276](https://pubmed.ncbi.nlm.nih.gov/15870276/): ELOVL4 mutations cause macular dystrophy. Nat Genet, 2005.
[23431055](https://pubmed.ncbi.nlm.nih.gov/23431055/): ELOVL4 deficiency in AD models. Proc Natl Acad Sci, 2013.
[25632052](https://pubmed.ncbi.nlm.nih.gov/25632052/): ELOVL4 in brain lipid metabolism. J Lipid Res, 2015.See Also
- [ELOVL4 Gene](/proteins/elovl4-protein)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Fatty Acid Metabolism](/mechanisms/fatty-acid-metabolism)
- [Proteins Index](/proteins)
- [Genes Index](/genes)
Overview
Elovl4 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Elovl4 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.
External Links
- [UniProt - ELOVL4](https://www.uniprot.org/uniprot/Q9GZR7)
- [NCBI Gene - ELOVL4](https://www.ncbi.nlm.nih.gov/gene/67834)
- [PDB - ELOVL4 Structure](https://www.rcsb.org/)
References
McMahon A, et al, (2005) (2005)
Liu L, et al, (2013) (2013)
Connor WE, et al, (2015) (2015)