COX5A explained

Cytochrome c oxidase subunit 5a is a protein that in humans is encoded by the COX5A gene. Cytochrome c oxidase 5A 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 COX5A gene, located on the q arm of chromosome 15 in position 24.1, is made up of 5 exons and is 17,880 base pairs in length.^[1] The COX5A protein weighs 17 kDa and is composed of 150 amino acids.^{[2] [3]} The protein is a subunit of Complex IV, which consists of 13 mitochondrial- and nuclear-encoded subunits.

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^[4]

Clinical significance

COX5A (this gene) and COX5B are involved in the regulation of cancer cell metabolism by Bcl-2. COX5A interacts specifically with Bcl-2, but not with other members of the Bcl-2 family, such as Bcl-xL, Bax or Bak.^[5]

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.^[6]

Further reading

• Williams SL, Valnot I, Rustin P, Taanman JW . Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1 . The Journal of Biological Chemistry . 279 . 9 . 7462–9 . Feb 2004 . 14607829 . 10.1074/jbc.M309232200 . free .
• Hughes GJ, Frutiger S, Paquet N, Pasquali C, Sanchez JC, Tissot JD, Bairoch A, Appel RD, Hochstrasser DF . Human liver protein map: update 1993 . Electrophoresis . 14 . 11 . 1216–22 . Nov 1993 . 8313870 . 10.1002/elps.11501401181. 33424554 .
• Kovalyov LI, Shishkin SS, Efimochkin AS, Kovalyova MA, Ershova ES, Egorov TA, Musalyamov AK . The major protein expression profile and two-dimensional protein database of human heart . Electrophoresis . 16 . 7 . 1160–9 . Jul 1995 . 7498159 . 10.1002/elps.11501601192. 32209361 .
• Yano M, Ueta Y, Murasaki A, Kanda H, Oka C, Kawaichi M . Binding of proteins to the PDZ domain regulates proteolytic activity of HtrA1 serine protease . The Biochemical Journal . 381 . Pt 3 . 895–904 . Aug 2004 . 15101818 . 1133901 . 10.1042/BJ20040435 .
• Hofmann S, Lichtner P, Schuffenhauer S, Gerbitz KD, Meitinger T . Assignment of the human genes coding for cytochrome c oxidase subunits Va (COX5A), VIc (COX6C) and VIIc (COX7C) to chromosome bands 15q25, 8q22-->q23 and 5q14 and of three pseudogenes (COX5AP1, COX6CP1, COX7CP1) to 14q22, 16p12 and 13q14-->q21 by FISH and radiation hybrid mapping . Cytogenetics and Cell Genetics . 83 . 3–4 . 226–7 . 1998 . 10072584 . 10.1159/000015185 .
• Cornelis MC, Monda KL, Yu K, Paynter N, Azzato EM, Bennett SN, Berndt SI, Boerwinkle E, Chanock S, Chatterjee N, Couper D, Curhan G, Heiss G, Hu FB, Hunter DJ, Jacobs K, Jensen MK, Kraft P, Landi MT, Nettleton JA, Purdue MP, Rajaraman P, Rimm EB, Rose LM, Rothman N, Silverman D, Stolzenberg-Solomon R, Subar A, Yeager M, Chasman DI, van Dam RM, Caporaso NE . Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption . PLOS Genetics . 7 . 4 . e1002033 . Apr 2011 . 21490707 . 3071630 . 10.1371/journal.pgen.1002033 . free .
• Rizzuto R, Nakase H, Zeviani M, DiMauro S, Schon EA . Subunit Va of human and bovine cytochrome c oxidase is highly conserved . Gene . 69 . 2 . 245–56 . Sep 1988 . 2853101 . 10.1016/0378-1119(88)90435-0.

External links

• • Mass spectrometry characterization of COX5A at COPaKB

Notes and References

1. Web site: Entrez Gene: Cytochrome c oxidase subunit Va .
2. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P . Integration of cardiac proteome biology and medicine by a specialized knowledgebase . Circulation Research . 113 . 9 . 1043–53 . Oct 2013 . 23965338 . 4076475 . 10.1161/CIRCRESAHA.113.301151 .
3. Web site: Cytochrome c oxidase subunit 5a . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) . 2018-07-18 . https://web.archive.org/web/20180719024437/https://amino.heartproteome.org/web/protein/P20674 . 2018-07-19 . dead .
4. 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 .
5. Chen ZX, Pervaiz S . Involvement of cytochrome c oxidase subunits Va and Vb in the regulation of cancer cell metabolism by Bcl-2 . Cell Death and Differentiation . 17 . 3 . 408–20 . Mar 2010 . 19834492 . 10.1038/cdd.2009.132 . free .
6. 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 .