Copper chaperone for superoxide dismutase (CCS)
The protein contains 274 amino acids for an estimated molecular weight of 29041 Da.
Delivers copper to copper zinc superoxide dismutase (SOD1). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| Found in a patient with congenital cataracts, hearing loss, neurodegen |
The reference OMIM entry for this protein is 603864
Copper chaperone for superoxide dismutase; ccs
CLONING
Copper (Cu) is required for aerobic life and yet, paradoxically, is highly toxic. This apparent contradiction has been rationalized by assuming that Cu, like other redox-active metals, is sequestered in nonreactive forms as it is transported into cells and moves through cellular compartments. Culotta et al. (1997) determined that one such Cu chaperone protein, Lys7, specifically delivers Cu to copper/zinc superoxide dismutase (Sod1; 147450) in S. cerevisiae. By searching EST databases, they identified cDNAs encoding the human Lys7 homolog, which they named CCS (copper chaperone for SOD1). The predicted 274-amino acid human protein is 28% identical to Lys7. CCS complemented a yeast Lys7 mutation, demonstrating that CCS is a functional homolog of Lys7. Northern blot analysis revealed that CCS was expressed as a 1.2-kb mRNA in all tissues and cell lines tested.MAPPING
Bartnikas et al. (2000) mapped the CCS gene to chromosome 11q13 by fluorescence in situ hybridization. They mapped the mouse Ccs gene to the proximal or centromeric end of chromosome 9 by haplotype analysis of a backcross panel.GENE FUNCTION
Casareno et al. (1998) found that the region of CCS encompassing amino acids 86-234 shares 47% identity with human SOD1. The residues of SOD1 identical to those of CCS include all of the known Cu and zinc ligands, the dimerization interface, and most of the amino acid residues mutated in familial ALS (105400). Binding assays and coimmunoprecipitation studies indicated that SOD1 and CCS directly interact in vitro and in vivo via the homologous domains in each protein. Immunofluorescence analysis experiments showed that CCS and SOD1 were distributed in an identical pattern throughout the cytoplasm and nucleus of mammalian cells. The authors proposed that Cu delivery to SOD1 is mediated via a direct interaction with CCS. Rae et al. (1999) demonstrated that the yeast Lys7 gene product, yCCS, activates Sod1 through direct insertion of the Cu cofactor. They found that the concentration of intracellular free Cu is limited to less than one free Cu ion per cell, suggesting that a pool of free Cu ions is not used in physiologic activation of metalloenzymes. Instead, Cu-dependent enzymes require accessory factors, such as the metallochaperone CCS, to compete with chelators and processes that sequester essentially all intracellular free Cu. Casareno et al. (1998) demonstrated that CCS interacts not only with wildtype SOD1 but also with SOD1 containing the common missense mutation resulting in familial amyotrophic lateral sclerosis (FALS), A4V (147450.0012), which is responsible for almost 50% of SOD1 mutations in FALS cases. The findings revealed a common mechanism whereby different SOD1 FALS mutants may result in neuronal injury and suggested a novel therapeutic approach in patients affected by this fatal disease. The delivery of copper by CCS to a target protein either unable or less able to incorporate this metal would inevitably lead to copper-mediated toxicity. Such a model is consistent with the failure to observe FALS in transgenic mice lacking SOD1, because under such circumstances no CCS-SOD1 interaction, and thus no copper transfer, will occur.MOLECULAR GENETICS
Huppke et al. (2012) identified mutations in the SLC33A1 gene (603690) in patients with an autosomal recessive disorder of congenital cataracts, hearing loss, and neurodegeneration (CCHLND; 614482). One of the patients, who had ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CCS
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603864 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed