CCS (Copper Chaperone for Superoxide Dismutase) is essential for the proper maturation of Cu/Zn superoxide dismutase (SOD1). CCS facilitates copper delivery to SOD1 and promotes the correct folding and dimerization of the enzyme, which is critical for antioxidant defense in neurons. This gene is located on chromosome 11q13.2 and encodes a protein that plays a critical role in cellular copper homeostasis.
| Property | Value |
|---|---|
| Gene Symbol | CCS |
| Full Name | Copper Chaperone for Superoxide Dismutase |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 9973 |
| OMIM | 603646 |
| Ensembl ID | ENSG00000129521 |
| UniProt | O15136 |
CCS performs essential functions in copper homeostasis and SOD1 maturation:
The CCS protein contains three domains: an N-terminal copper-binding domain, a central domain that interacts with SOD1, and a C-terminal domain involved in dimerization. The protein forms homodimers and facilitates the formation of functional SOD1 homodimers through a series of copper-mediated interactions[1].
CCS is directly implicated in ALS pathogenesis through its role in SOD1 maturation:
CCS is expressed in:
In the brain, CCS is particularly enriched in regions with high metabolic demand and oxidative stress susceptibility.
| Approach | Description | Status |
|---|---|---|
| Copper modulation | Modulate cellular copper to influence CCS-SOD1 interaction | Research |
| Gene therapy | Target CCS expression for ALS | Preclinical |
| Antioxidant therapy | Enhance SOD1 activity through CCS pathway | Research |
Wong PC, et al. Copper chaperone for superoxide dismutase (CCS) is essential for development. Proceedings of the National Academy of Sciences. 2000. ↩︎
Subramaniam JR, et al. The copper chaperone CCS is required for activation of mutant SOD1 associated with familial ALS. Neuron. 2002. ↩︎
Rothstein JD. Cord function in amyotrophic lateral sclerosis: mechanisms and role of CCS. Neurobiology of Aging. 2009. ↩︎