CCS transfers Cu to SOD1 and oxidizes cysteine residues in SOD1

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser

Copper chaperone of superoxide dismutase (CCS) transfers a copper(I) atom to a SOD1 monomer that already contains a Zn atom. After initial heterodimerization between SOD1 and CCS, the copper atom is transferred, intramolecular cysteine disulfide bonds are formed in SOD1, and SOD1 dimerizes (Banci et al. 2012, Casareno et al. 1998, Culotta et al. 1997, Rae et al. 2001, Brown et al. 2004, Carroll et al. 2006, Kawamata and Manfredi 2008). The transfer of copper to SOD1 requires oxygen but it is unknown at which step the oxygen acts (Brown et al. 2004). There is also a CCS-independent, oxygen-independent pathway of maturation of SOD1 (Leitch et al. 2009) whose molecular details and physiological role are not well characterized.

Literature References
PubMed ID Title Journal Year
9726962 The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase

Casareno, RL, Waggoner, D, Gitlin, JD

J. Biol. Chem. 1998
9295278 The copper chaperone for superoxide dismutase

Culotta, VC, Klomp, LW, Strain, J, Casareno, RL, Krems, B, Gitlin, JD

J. Biol. Chem. 1997
15064408 Oxygen and the copper chaperone CCS regulate posttranslational activation of Cu,Zn superoxide dismutase

Brown, NM, Torres, AS, Doan, PE, O'Halloran, TV

Proc. Natl. Acad. Sci. U.S.A. 2004
22869735 Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS)

Banci, L, Bertini, I, Cantini, F, Kozyreva, T, Massagni, C, Palumaa, P, Rubino, JT, Zovo, K

Proc. Natl. Acad. Sci. U.S.A. 2012
16880213 The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu,Zn superoxide dismutase

Carroll, MC, Outten, CE, Proescher, JB, Rosenfeld, L, Watson, WH, Whitson, LJ, Hart, PJ, Jensen, LT, Cizewski Culotta, V

J. Biol. Chem. 2006
18703498 Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria

Kawamata, H, Manfredi, G

Hum. Mol. Genet. 2008
19542232 Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS

Leitch, JM, Jensen, LT, Bouldin, SD, Outten, CE, Hart, PJ, Culotta, VC

J. Biol. Chem. 2009
11018045 Mechanism of Cu,Zn-superoxide dismutase activation by the human metallochaperone hCCS

Rae, TD, Torres, AS, Pufahl, RA, O'Halloran, TV

J. Biol. Chem. 2001
Participant Of
Catalyst Activity
Catalyst Activity
protein disulfide oxidoreductase activity of CCS:Zn2+:2xCu1+:SOD1:Zn2+ [cytosol]
Physical Entity
Orthologous Events