COX6A2 explained

Cytochrome c oxidase subunit VIa polypeptide 2 is a protein that in humans is encoded by the COX6A2 gene. Cytochrome c oxidase 6A2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.^[1]

Structure

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. The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids.^[2] 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.

Function

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.

Summary reaction:

4 Fe²⁺-cytochrome c + 8 H⁺_in + O₂ → 4 Fe³⁺-cytochrome c + 2 H₂O + 4 H⁺_out^[3]

Clinical significance

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 (ΔΨ_m) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.^[4]

Further reading

• Fabrizi GM, Sadlock J, Hirano M, Mita S, Koga Y, Rizzuto R, Zeviani M, Schon EA . Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase . Gene . 119 . 2 . 307–12 . Oct 1992 . 1327966 . 10.1016/0378-1119(92)90288-z.
• Hey Y, Hoggard N, Burt E, James LA, Varley JM . 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 . 9284905 . 1997 . 10.1159/000134565.
• Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, Toppo S, Trevisan S, Scarso S, Valle G . Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization . Genome Research . 6 . 1 . 35–42 . Jan 1996 . 8681137 . 10.1101/gr.6.1.35. free .
• Taanman JW, Hall RE, Tang C, Marusich MF, Kennaway NG, Capaldi RA . 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 . Nov 1993 . 8241294 . 10.1016/0925-4439(93)90128-n.
• Bachman NJ, Riggs PK, Siddiqui N, Makris GJ, Womack JE, Lomax MI . 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 . May 1997 . 9177785 . 10.1006/geno.1997.4687 .
• Lecoeur H, Borgne-Sanchez A, Chaloin O, El-Khoury R, Brabant M, Langonné A, Porceddu M, Brière JJ, Buron N, Rebouillat D, Péchoux C, Deniaud A, Brenner C, Briand JP, Muller S, Rustin P, Jacotot E . HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase . Cell Death & Disease . 3 . 3 . e282 . 2012 . 22419111 . 3317353 . 10.1038/cddis.2012.21 .

External links

• • Mass spectrometry characterization of COX6A2 at COPaKB

Notes and References

1. Web site: Entrez Gene: Cytochrome c oxidase subunit VIa polypeptide 2 .
2. Web site: Cytochrome c oxidase subunit 6A2, mitochondrial . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) . 2018-07-18 . https://web.archive.org/web/20180719161720/https://amino.heartproteome.org/web/protein/Q02221 . 2018-07-19 . dead .
3. Book: Donald . Voet . Judith G. . Voet . Charlotte W. . Pratt . vanc . Donald Voet . Judith G. Voet . Fundamentals of Biochemistry: Life at the Molecular Level . 2013 . Wiley . Hoboken, NJ . 978-0-470-54784-7 . Chapter 18 . 581–620 . 4th .
4. Lecoeur H, Borgne-Sanchez A, Chaloin O, El-Khoury R, Brabant M, Langonné A, Porceddu M, Brière JJ, Buron N, Rebouillat D, Péchoux C, Deniaud A, Brenner C, Briand JP, Muller S, Rustin P, Jacotot E . HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase . Cell Death & Disease . 3 . 3 . e282 . 2012 . 22419111 . 3317353 . 10.1038/cddis.2012.21 .