InterPro domain: IPR036639

Cytochrome c oxidase (CcO)( 1.9.3.1 ), the terminal oxidase in the respiratory chains of eukaryotes and most bacteria, is a multi-chain transmembrane protein located in the inner membrane of mitochondria and the cell membrane of prokaryotes. It catalyzes the reduction of O2 and simultaneously pumps protons across the membrane. The number of subunits varies from three to five in bacteria and up to 13 in mammalian mitochondria. Subunits I, II, and III of mammalian CcO are encoded within the mitochondrial genome and the remaining 10 subunits are encoded within the nuclear genome. Found only in eukaryotes, subunit IV is the largest of the nuclear-encoded subunits. It binds ATP at the matrix side, leading to an allosteric inhibition of enzyme activity at high intramitochondrial ATP/ADP ratios. In mammals, subunit IV has a lung-specific isoform and a ubiquitously expressed isoform [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ].

This superfamily is composed of cytochrome c oxidase subunit 4 [ 13 ], subunits 5A and 5B [ 13 ], subunit 6 [ 14 ] and subunit 7. Proteins in this entry also include the yeast COX IV subunit, Mtc3 (maintenance of telomere cappining 3) protein [ 15 , 16 ].

1. Mammalian subunit IV isoforms of cytochrome c oxidase. Gene 267, 111-23
2. Protein kinase Cepsilon interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning. Biochem. J. 393, 191-9
3. Mitochondrial proteome: altered cytochrome c oxidase subunit levels in prostate cancer. Proteomics 3, 1801-10
4. Episodic positive selection in ape cytochrome c oxidase subunit IV. Mol. Biol. Evol. 19, 1812-5
5. A third isoform of cytochrome c oxidase subunit VIII is present in mammals. Gene 312, 95-102
6. Mitochondrial energy metabolism is regulated via nuclear-coded subunits of cytochrome c oxidase. Free Radic. Biol. Med. 29, 211-21
7. Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Prog. Nucleic Acid Res. Mol. Biol. 61, 309-44
8. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A. Science 272, 1136-44
9. Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process. Am. J. Physiol., Cell Physiol. 291, C1129-47
10. Copper trafficking to the mitochondrion and assembly of copper metalloenzymes. Biochim. Biophys. Acta 1763, 759-72
11. Biogenesis of cytochrome c oxidase. Mitochondrion 5, 363-88
12. Cytochrome c oxidase, ligands and electrons. J. Inorg. Biochem. 99, 324-36
13. Structural analysis of two genes encoding divergent forms of yeast cytochrome c oxidase subunit V. Mol. Cell. Biol. 7, 3511-9
14. Characterization of a cDNA encoding subunit VI of cytochrome c oxidase from the slime mold Dictyostelium discoideum. Biochim. Biophys. Acta 1089, 386-8
15. A genomewide suppressor and enhancer analysis of cdc13-1 reveals varied cellular processes influencing telomere capping in Saccharomyces cerevisiae. Genetics 180, 2251-66
16. Global analysis of protein localization in budding yeast. Nature 425, 686-91