The COX6A2 gene, located on the p arm of chromosome 16 in position 11.12, contains 3 exons and is 698 base pairs in length.[5] The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids.[6][7] The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. This nuclear gene encodes polypeptide 2 (heart/muscle isoform) of subunit VIa, and polypeptide 2 is present only in striated muscles. Polypeptide 1 (liver isoform) of subunit VIa is encoded by a different gene, COX6A1, and is found in all non-muscle tissues. These two polypeptides share 66% amino acid sequence identity.[5]
Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force. The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.[5]
Summary reaction:
4 Fe2+-cytochrome c + 8 H+in + O2 → 4 Fe3+-cytochrome c + 2 H2O + 4 H+out[8]
The Trans-activator of transcription protein (Tat) of human immunodeficiency virus (HIV) inhibits cytochrome c oxidase (COX) activity in permeabilized mitochondria isolated from both mouse and human liver, heart, and brain samples. Rapid loss of membrane potential (ΔΨm) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.[9]
^Voet D, Voet JG, Pratt CW (2013). "Chapter 18". Fundamentals of Biochemistry: Life at the Molecular Level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN978-0-470-54784-7.
Fabrizi GM, Sadlock J, Hirano M, Mita S, Koga Y, Rizzuto R, Zeviani M, Schon EA (Oct 1992). "Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase". Gene. 119 (2): 307–12. doi:10.1016/0378-1119(92)90288-z. PMID1327966.
Hey Y, Hoggard N, Burt E, James LA, Varley JM (1997). "Assignment of COX6A1 to 6p21 and a pseudogene (COX6A1P) to 1p31.1 by in situ hybridization and somatic cell hybrids". Cytogenetics and Cell Genetics. 77 (3–4): 167–8. doi:10.1159/000134565. PMID9284905.
Taanman JW, Hall RE, Tang C, Marusich MF, Kennaway NG, Capaldi RA (Nov 1993). "Tissue distribution of cytochrome c oxidase isoforms in mammals. Characterization with monoclonal and polyclonal antibodies". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1225 (1): 95–100. doi:10.1016/0925-4439(93)90128-n. PMID8241294.
Bachman NJ, Riggs PK, Siddiqui N, Makris GJ, Womack JE, Lomax MI (May 1997). "Structure of the human gene (COX6A2) for the heart/muscle isoform of cytochrome c oxidase subunit VIa and its chromosomal location in humans, mice, and cattle". Genomics. 42 (1): 146–51. doi:10.1006/geno.1997.4687. PMID9177785.
