CYP2U1 Protein — Cytochrome P450 2U1

CYP2U1 Protein — Cytochrome P450 2U1

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CYP2U1 Protein — Cytochrome P450 2U1</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>CYP2U1 (Cytochrome P450 2U1)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>CYP2U1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5K1</td>
</tr>
<tr>
<td class="label">PDB ID</td>
<td>5T7Q</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>501 aa (~56 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cytochrome P450 family</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">20-HETE inhibitors</td>
<td>Block 20-HETE synthesis</td>
</tr>
<tr>
<td class="label">CYP2U1 siRNA</td>
<td>Reduce expression</td>
</tr>
<tr>
<td class="label">20-HETE antagonists</td>
<td>Receptor blockade</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Cyp2U1 Protein — Cytochrome P450 2U1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

CYP2U1 Protein — Cytochrome P450 2U1

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CYP2U1 Protein — Cytochrome P450 2U1</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>CYP2U1 (Cytochrome P450 2U1)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>CYP2U1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5K1</td>
</tr>
<tr>
<td class="label">PDB ID</td>
<td>5T7Q</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>501 aa (~56 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Endoplasmic reticulum membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>Cytochrome P450 family</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">20-HETE inhibitors</td>
<td>Block 20-HETE synthesis</td>
</tr>
<tr>
<td class="label">CYP2U1 siRNA</td>
<td>Reduce expression</td>
</tr>
<tr>
<td class="label">20-HETE antagonists</td>
<td>Receptor blockade</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Cyp2U1 Protein — Cytochrome P450 2U1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about CYP2U1 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.

Structure

CYP2U1 is a membrane-anchored cytochrome P450 with:

• N-terminal transmembrane helix (residues 1-20) - anchors to ER membrane
• Catalytic domain (residues 30-480) - contains heme cofactor
• C-terminal region (residues 480-501) - cytosolic tail

• Contains the heme-binding motif (FGxGPRNCIG)
• Unusual substrate access channel compared to typical P450s
• Lacks typical substrate recognition sites (SRS)

Normal Function

CYP2U1 is a specialized cytochrome P450 that metabolizes:

Arachidonic Acid Metabolism

• 20-HETE synthase - primary activity
• Hydroxylates arachidonic acid at ω-position
• Produces 20-hydroxyeicosatetraenoic acid (20-HETE)

Polyunsaturated Fatty Acids

• Metabolizes EPA (eicosapentaenoic acid)
• Metabolizes DHA (docosahexaenoic acid)
• Produces bioactive lipid mediators

20-HETE Functions

• Vasoconstriction - regulates blood pressure
• Sodium transport - modulates renal function
• Inflammation - pro-inflammatory mediator
• Cell proliferation - affects growth and survival

Role in Disease

Hereditary Spastic Paraplegia (SPG56)

CYP2U1 mutations cause HSP through:

• Loss of 20-HETE production
• Impaired lipid signaling in [neurons](/entities/neurons)
• Axonal degeneration in corticospinal tract

Neuroinflammation

CYP2U1-derived 20-HETE:

• Promotes microglial activation
• Modulates [blood-brain barrier](/entities/blood-brain-barrier)
• Enhances oxidative stress

Therapeutic Targeting

Key Publications

See Also

• [CYP2U1 Gene](/proteins/cyp2u1-protein)
• [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
• [Cytochrome P450](/cyp2u1-—-cytochrome-p450-family-2-subfamily-u-member-1)
• [Arachidonic Acid Metabolism](/mechanisms/arachidonic-acid-metabolism)
• [Neuroinflammation](/mechanisms/neuroinflammation-pathway)

External Links

• [UniProt: CYP2U1](https://www.uniprot.org/uniprot/Q9Y5K1)
• [PDB: CYP2U1](https://www.rcsb.org/structure/5T7Q)
• [NCBI Protein: CYP2U1](https://www.ncbi.nlm.nih.gov/protein/Q9Y5K1)

Disease Associations

Hereditary Spastic Paraplegia (SPG56)

• CYP2U1 mutations cause AR-SPG56
• First described in 2012 (Tesson et al.)
• Characterized by:
• Early-onset spastic paraplegia
• Cognitive impairment
• Thin corpus callosum
• Cerebellar ataxia

Neurodegeneration Mechanisms

• 20-HETE dysregulation affects:
• Cerebral blood flow autoregulation
• Neurovascular coupling
• Oxidative stress in neurons
• Inflammatory responses

Alzheimer's Disease

• Elevated 20-HETE in AD brains
• Associated with vascular dysfunction
• Potential biomarker for vascular cognitive impairment

Parkinson's Disease

• CYP2U1 expression altered in PD
• May affect dopamine neuron survival
• 20-HETE neurotoxicity at high concentrations

Therapeutic Approaches

20-HETE Inhibitors

• HET0016 - selective 20-HETE synthesis inhibitor
• TS011 - potent 20-HETE inhibitor
• Show neuroprotective effects in preclinical models

Gene Therapy

• AAV-mediated CYP2U1 delivery
• CRISPR-based approaches for SPG56
• Under investigation

Small Molecule Modulators

• 20-HETE receptor antagonists
• PPAR agonists affecting CYP2U1 expression
• Nrf2 activators upregulate CYP2U1

Research Directions

• Understanding CYP2U1 mutation spectrum in SPG56
• Developing brain-penetrant 20-HETE inhibitors
• Biomarker potential of 20-HETE in neurodegenerative diseases
• Elucidating CYP2U1 function in specific neuronal populations

Background

The study of Cyp2U1 Protein — Cytochrome P450 2U1 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.

Allen Brain Atlas Resources

Expression data for CYP2U1 in the human brain can be explored through the following Allen Brain Atlas resources:

• [Allen Human Brain Atlas - CYP2U1 Expression](https://human.brain-map.org/microarray/search/show?search_term=CYP2U1): Gene expression data across brain regions
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/): Developmental expression patterns for CYP2U1

References