The SLC31A2 gene encodes Copper Transporter 2 (CTR2), a low-affinity copper uptake protein that works in conjunction with CTR1 (encoded by [SLC31A1](/genes/slc31a1)) to regulate cellular copper homeostasis [@ctr]. While CTR1 is the high-affinity copper transporter, CTR2 has lower affinity but higher capacity, and the two transporters together ensure appropriate copper uptake under varying copper concentrations [@ctra].
CTR2 is expressed in various tissues and plays complementary roles in copper acquisition, particularly in tissues where CTR1 expression is low or under conditions of high copper availability [@copper].
Function and Mechanism
Low-Affinity Copper Transport
CTR2, like CTR1, facilitates the uptake of Cu⁺ ions across the plasma membrane. However, CTR2 has significantly lower affinity for copper (Kd in the micromolar range compared to nanomolar for CTR1). This difference in affinity means:
CTR1: Dominates copper uptake at low extracellular copper concentrations
CTR2: Becomes more important when copper concentrations are elevated [@affinity]
Substrate Specificity
CTR2 can transport:
Copper (Cu⁺)
Possibly other metal ions, though with lower affinity
Silver (Ag⁺) as a copper mimetic [@ctrb]
Regulation
CTR2 expression is regulated by cellular copper status, but with different dynamics than CTR1:
Different transcriptional control mechanisms than CTR1 [@regulation]
Expression Pattern
CTR2 is expressed in various tissues, often complementary to CTR1:
Brain: [Neurons](/entities/neurons) and glial cells
Liver: Hepatocytes
Kidney: Tubular cells
Intestine: Enterocytes
Testis: Spermatogenic cells
Tumor tissues: Often upregulated in cancers [@tissue]
Relationship with CTR1
CTR1 and CTR2 work together to maintain copper homeostasis:
Complementary function: At low copper, CTR1 dominates; at high copper, CTR2 contributes more
Redundancy: CTR2 can partially compensate for CTR1 deficiency
Tissue-specific roles: Different tissues rely differently on each transporter [@ctrc]
Role in Disease
Cancer
CTR2 is frequently overexpressed in various cancers, where it may support the high copper demand of proliferating tumor cells. CTR2 expression in tumors correlates with:
Increased cell proliferation
Enhanced angiogenesis
Resistance to copper-based chemotherapy [@ctrd]
Neurodegeneration
While less studied than CTR1 in neurodegeneration, CTR2 may be relevant:
Alzheimer's disease: May contribute to copper dysregulation in the brain
Parkinson's disease: Potential role in dopaminergic neuron copper handling
Aging: Changes in CTR2 expression may affect neuronal copper homeostasis [@coppera]
Menkes and Wilson Disease
CTR2 may modify the severity of copper transport disorders:
Can partially compensate for ATP7A (Menkes) or ATP7B (Wilson) dysfunction
May influence disease progression and therapeutic response [@ctre]
Interactions with Other Proteins
CTR2 interacts with several copper homeostasis proteins: