EC - Cytochrome-c oxidase

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IntEnz Enzyme Nomenclature


Accepted name:
cytochrome-c oxidase
Other names:
NADH cytochrome c oxidase
Warburg's respiratory enzyme
complex IV (mitochondrial electron transport)
cytochrome a3
cytochrome aa3
cytochrome oxidase
ferrocytochrome c oxidase
indophenol oxidase
cytochrome caa3
cytochrome bb3
cytochrome cbb3
cytochrome ba3
Systematic name:
ferrocytochrome-c:oxygen oxidoreductase




An oligomeric membrane heme-Cu:O2 reductase-type enzyme that terminates the respiratory chains of aerobic and facultative aerobic organisms. The reduction of O2 to water is accompanied by the extrusion of four protons. The cytochrome-aa3 enzymes of mitochondria and many bacterial species are the most abundant group, but other variations, such as the bacterial cytochrome-cbb3 enzymes, also exist. All of the variants have a conserved catalytic core subunit (subunit I) that contains a low-spin heme (of a- or b-type), a binuclear metal centre composed of a high-spin heme iron (of a-, o-, or b-type heme, referred to as a3, o3 or b3 heme), and a Cu atom (CuB). Besides subunit I, the enzyme usually has at least two other core subunits: subunit II is the primary electron acceptor; subunit III usually does not contain any cofactors, but in the case of cbb3-type enzymes it is a diheme C-type cytochrome. While most bacterial enzymes consist of only 3-4 subunits, the mitochondrial enzyme is much more complex and contains 14 subunits. Formerly EC

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , NIST 74 , UniPathway
Protein domains and families: PROSITE:PDOC00074 , PROSITE:PDOC00075 , PROSITE:PDOC00663
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004129
CAS Registry Number: 9001-16-5
UniProtKB/Swiss-Prot: (757) [show] [UniProt]


  1. Keilin, D. and Hartree, E.F.
    Cytochrome oxidase.
    Proc. R. Soc. Lond. B Biol. Sci. 125 : 171-186 (1938).
  2. Keilin, D. and Hartree, E.F.
    Cytochrome and cytochrome oxidase.
    Proc. R. Soc. Lond. B Biol. Sci. 127 : 167-191 (1939).
  3. Wainio, W.W., Eichel, B. and Gould, A.
    Ion and pH optimum for the oxidation of ferrocytochrome c by cytochrome c oxidase in air.
    J. Biol. Chem. 235 : 1521-1525 (1960).
  4. Yonetani, T.
    Studies on cytochrome oxidase. II. Steady state properties.
    J. Biol. Chem. 235 : 3138-3243 (1960). [PMID: 13787372]
  5. Yonetani, T.
    Studies on cytochrome oxidase. III. Improved preparation and some properties.
    J. Biol. Chem. 236 : 1680-1688 (1961). [PMID: 13787373]
  6. Henning, W., Vo, L., Albanese, J., Hill, B. C.
    High-yield purification of cytochrome aa3 and cytochrome caa3 oxidases from Bacillus subtilis plasma membranes.
    Biochem. J. 309 ( Pt 1) : 279-283 (1995). [PMID: 7619069]
  7. Keightley, J. A., Zimmermann, B. H., Mather, M. W., Springer, P., Pastuszyn, A., Lawrence, D. M., Fee, J. A.
    Molecular genetic and protein chemical characterization of the cytochrome ba3 from Thermus thermophilus HB8.
    J. Biol. Chem. 270 : 20345-20358 (1995). [PMID: 7657607]
  8. Ducluzeau, A. L., Ouchane, S., Nitschke, W.
    The cbb3 oxidases are an ancient innovation of the domain bacteria.
    Mol. Biol. Evol. 25 : 1158-1166 (2008). [PMID: 18353797]

[EC created 1961 as as EC, modified 2000, transferred 2019 to EC]