“COX6A2”的意思、由来-开放百科全书

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.^[1] The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids.^[2]^[3] 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.^[1]

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.^[1]

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.^[5]

References

1. ^¹²³{{cite web | title = Entrez Gene: Cytochrome c oxidase subunit VIa polypeptide 2 | url = https://www.ncbi.nlm.nih.gov/gene/1339 }}
2. ^]{{cite journal | vauthors = 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 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
3. ^{{cite web | url = https://amino.heartproteome.org/web/protein/Q02221 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Cytochrome c oxidase subunit 6A2, mitochondrial }}
4. ^{{cite book | first1 = Donald | last1 = Voet | first2 = Judith G. | last2 = Voet | first3 = Charlotte W. | last3 = Pratt | name-list-format = vanc | author1-link = Donald Voet | author2-link = Judith G. Voet | title = Fundamentals of Biochemistry: Life at the Molecular Level | date = 2013 | publisher = Wiley | location = Hoboken, NJ | isbn = 978-0-470-54784-7 | chapter = Chapter 18 | pages = 581–620 | edition = 4th }}
5. ^{{cite journal | vauthors = 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 | title = HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase | journal = Cell Death & Disease | volume = 3 | issue = 3 | pages = e282 | year = 2012 | pmid = 22419111 | pmc = 3317353 | doi = 10.1038/cddis.2012.21 }}

Further reading

{{cite journal | vauthors = Fabrizi GM, Sadlock J, Hirano M, Mita S, Koga Y, Rizzuto R, Zeviani M, Schon EA | title = Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase | journal = Gene | volume = 119 | issue = 2 | pages = 307–12 | date = Oct 1992 | pmid = 1327966 | doi=10.1016/0378-1119(92)90288-z}}

{{cite journal | vauthors = Hey Y, Hoggard N, Burt E, James LA, Varley JM | title = Assignment of COX6A1 to 6p21 and a pseudogene (COX6A1P) to 1p31.1 by in situ hybridization and somatic cell hybrids | journal = Cytogenetics and Cell Genetics | volume = 77 | issue = 3–4 | pages = 167–8 | pmid = 9284905 | year = 1997 | doi=10.1159/000134565}}

{{cite journal | vauthors = Lanfranchi G, Muraro T, Caldara F, Pacchioni B, Pallavicini A, Pandolfo D, Toppo S, Trevisan S, Scarso S, Valle G | title = Identification of 4370 expressed sequence tags from a 3'-end-specific cDNA library of human skeletal muscle by DNA sequencing and filter hybridization | journal = Genome Research | volume = 6 | issue = 1 | pages = 35–42 | date = Jan 1996 | pmid = 8681137 | doi=10.1101/gr.6.1.35}}

{{cite journal | vauthors = Taanman JW, Hall RE, Tang C, Marusich MF, Kennaway NG, Capaldi RA | title = Tissue distribution of cytochrome c oxidase isoforms in mammals. Characterization with monoclonal and polyclonal antibodies | journal = Biochimica et Biophysica Acta | volume = 1225 | issue = 1 | pages = 95–100 | date = Nov 1993 | pmid = 8241294 | doi=10.1016/0925-4439(93)90128-n}}

{{cite journal | vauthors = Bachman NJ, Riggs PK, Siddiqui N, Makris GJ, Womack JE, Lomax MI | title = 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 | journal = Genomics | volume = 42 | issue = 1 | pages = 146–51 | date = May 1997 | pmid = 9177785 | doi = 10.1006/geno.1997.4687 }}

{{cite journal | vauthors = 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 | title = HIV-1 Tat protein directly induces mitochondrial membrane permeabilization and inactivates cytochrome c oxidase | journal = Cell Death & Disease | volume = 3 | issue = 3 | pages = e282 | year = 2012 | pmid = 22419111 | pmc = 3317353 | doi = 10.1038/cddis.2012.21 }}

Structure

Function

Clinical significance

References

Further reading

External links