COX6A2
| COX6A2 | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||||||
| Aliases | COX6A2, COX6AH, COXVIAH, cytochrome c oxidase subunit 6A2 | ||||||||||||||||
| External IDs | MGI: 104649 HomoloGene: 38020 GeneCards: COX6A2 | ||||||||||||||||
| |||||||||||||||||
| Orthologs | |||||||||||||||||
| Species | Human | Mouse | |||||||||||||||
| Entrez | |||||||||||||||||
| Ensembl | |||||||||||||||||
| UniProt | |||||||||||||||||
| RefSeq (mRNA) | |||||||||||||||||
| RefSeq (protein) | |||||||||||||||||
| Location (UCSC) | Chr 16: 31.43 – 31.43 Mb | Chr 7: 128.21 – 128.21 Mb | |||||||||||||||
| PubMed search | [1] | [2] | |||||||||||||||
| Wikidata | |||||||||||||||||
| View/Edit Human | View/Edit Mouse |
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.[3]
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.[3] The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids.[4][5] 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.[3]
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.[3]
Summary reaction:
- 4 Fe2+-cytochrome c + 8 H+in + O2 → 4 Fe3+-cytochrome c + 2 H2O + 4 H+out[6]
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 (ΔΨm) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.[7]
References
- ↑ "Human PubMed Reference:".
- ↑ "Mouse PubMed Reference:".
- 1 2 3 4 "Entrez Gene: Cytochrome c oxidase subunit VIa polypeptide 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 (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475
. PMID 23965338. - ↑ "Cytochrome c oxidase subunit 6A2, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ↑ 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. ISBN 978-0-470-54784-7.
- ↑ 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 (2012). "HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase". Cell Death & Disease. 3 (3): e282. doi:10.1038/cddis.2012.21. PMC 3317353. PMID 22419111.
Further reading
- 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. PMID 1327966.
- 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. PMID 9284905.
- Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, Toppo S, Trevisan S, Scarso S, Valle G (Jan 1996). "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. doi:10.1101/gr.6.1.35. PMID 8681137.
- 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. 1225 (1): 95–100. doi:10.1016/0925-4439(93)90128-n. PMID 8241294.
- 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. PMID 9177785.
- 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 (2012). "HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase". Cell Death & Disease. 3 (3): e282. doi:10.1038/cddis.2012.21. PMC 3317353. PMID 22419111.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.