SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SLC31A1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 31 Member 1 (Copper Transporter 1)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>9q32</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[10551](https://www.ncbi.nlm.nih.gov/gene/10551)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[603085](https://www.omim.org/entry/603085)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000137767</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[O15431](https://www.uniprot.org/uniprot/O15431)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Menkes disease (potential modifier), Wilson disease, Amyotrophic lateral sclerosis</td>
</tr>
</table>

{{.infobox .infobox-gene}}

Overview

SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SLC31A1 — Solute Carrier Family 3 Member 1A1 (SLC31A1)</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SLC31A1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Solute Carrier Family 31 Member 1 (Copper Transporter 1)</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>9q32</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>[10551](https://www.ncbi.nlm.nih.gov/gene/10551)</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>[603085](https://www.omim.org/entry/603085)</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000137767</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[O15431](https://www.uniprot.org/uniprot/O15431)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>Menkes disease (potential modifier), Wilson disease, Amyotrophic lateral sclerosis</td>
</tr>
</table>

{{.infobox .infobox-gene}}

Overview

The SLC31A1 gene encodes Copper Transporter 1 (CTR1), a high-affinity plasma membrane copper uptake protein essential for cellular copper homeostasis [@ctr]. CTR1 is the primary gateway for copper acquisition in most cell types, mediating the rapid uptake of copper required for the function of copper-dependent enzymes throughout the body [@copper].

Copper is an essential trace element required for the activity of numerous enzymes critical to energy metabolism, antioxidant defense, neurotransmitter synthesis, and iron metabolism. However, excess copper is highly toxic, making the tight regulation provided by CTR1 and other copper transporters crucial for cellular health [@coppera].

Function and Mechanism

Copper Uptake

CTR1 functions as a high-affinity copper transporter, facilitating the import of Cu⁺ ions (the reduced form of copper) across the plasma membrane. The transporter operates as a trimer, forming a pore that conducts copper ions driven by the transmembrane copper gradient [@structure].

Key features of CTR1-mediated copper uptake:

• High affinity: Kd in the low micromolar to nanomolar range
• Rapid kinetics: Enables efficient copper acquisition even at low extracellular concentrations
• Regulated expression: CTR1 levels are adjusted based on cellular copper status
• Endocytosis: Copper uptake triggers CTR1 internalization and degradation [@regulation]

Interaction with Copper Chaperones

Once inside the cell, copper is immediately handed off to copper chaperones that direct it to specific destinations:

• CCS (Copper Chaperone for SOD): Delivers copper to Cu/Zn superoxide dismutase (SOD1)
• COX17: Delivers copper to cytochrome c oxidase in mitochondria
• ATOX1: Delivers copper to copper-transporting ATPases (ATP7A, ATP7B) [@copperb]

Expression Pattern

CTR1 is expressed in virtually all tissues, with particularly high expression in:

• Intestine: Primary site of dietary copper absorption
• Liver: Central organ for copper metabolism
• Brain: [Neurons](/entities/neurons) and endothelial cells of the [blood-brain barrier](/entities/blood-brain-barrier)
• Kidney: Involved in copper reabsorption
• Heart and muscle: High metabolic demand tissues [@ctra]

Role in Neurodegeneration

Copper in Alzheimer's Disease

Copper dysregulation is strongly implicated in Alzheimer's disease pathogenesis:

• [Amyloid-beta](/proteins/amyloid-beta) interaction: Copper binds to amyloid-beta peptides, promoting aggregation and neurotoxicity [@copperc]
• Oxidative stress: Copper-catalyzed Fenton reactions generate [reactive oxygen species](/entities/reactive-oxygen-species) (ROS)
• Metal homeostasis disruption: Alzheimer's disease brains show altered copper levels
• CTR1 expression changes: CTR1 expression is modified in Alzheimer's disease brains [@copperd]

Copper in Parkinson's Disease

Copper also plays a role in Parkinson's disease:

• Alpha-synuclein interaction: Copper binds to alpha-synuclein, accelerating its aggregation [@coppere]
• Mitochondrial function: Copper is required for proper mitochondrial electron transport
• Dopaminergic neuron vulnerability: Copper metabolism affects dopamine neuron survival [@copperf]

Amyotrophic Lateral Sclerosis (ALS)

CTR1 may be relevant to ALS pathogenesis:

• Copper metabolism is altered in ALS
• CTR1 expression affects mutant SOD1 toxicity in familial ALS models
• Copper chelation strategies have been explored as potential therapies [@copperg]

Disease Associations

Menkes Disease

While Menkes disease is primarily caused by mutations in ATP7A (a copper-transporting ATPase), CTR1 function can modify disease severity. Reduced CTR1 expression can exacerbate copper deficiency in Menkes disease [@ctrc].

Wilson Disease

Wilson disease, caused by ATP7B mutations, involves copper overload. CTR1 expression may influence the rate of copper accumulation and disease progression [@ctrd].

Cancer

CTR1 is frequently upregulated in cancers, where copper is needed for proliferation and angiogenesis. CTR1 expression correlates with tumor growth and metastatic potential [@ctre].

Therapeutic Implications

CTR1 is a potential therapeutic target:

• Copper chelation therapy: For conditions of copper overload
• Copper supplementation: For conditions of copper deficiency
• Drug delivery: CTR1 can be exploited for targeted delivery of copper-based chemotherapeutic agents [@targeting]

See Also

• [SLC31A2](/genes/slc31a2) - CTR2 (low-affinity copper transporter)](/genes)
• [ATP7A](/proteins/atp7a-protein) - Menkes disease protein](/proteins)
• [ATP7B](/proteins/atp7b-protein) - Wilson disease protein](/proteins)
• [Copper and Alzheimer's disease](/diseases/alzheimers-disease)
• [Alpha-synuclein](/proteins/alpha-synuclein)

References