| 词条 | Cytochrome c oxidase subunit II |
| 释义 |
| Symbol = COX2_TM | Name = Cytochrome c oxidase subunit II, transmembrane domain | image =1qle_opm.png | width = | caption = Bacterial cytochrome c oxidase complex. Subunit II indicated by blue. | Pfam= PF02790 | InterPro= IPR011759 | SMART= | PROSITE = PDOC00075 | SCOP = 1occ | TCDB = 3.D.4 | OPM family= 4 | OPM protein= 1v55 }}{{Pfam_box | Symbol = COX2 | Name = Cytochrome C oxidase subunit II, periplasmic domain | image = | width = | caption = | Pfam= PF00116 | InterPro= IPR002429 | SMART= | PROSITE = | SCOP = | TCDB = | OPM family= | OPM protein= | CDD = cd13912 }} Cytochrome c oxidase subunit 2, also known as cytochrome c oxidase polypeptide II, is a protein that in humans is encoded by the MT-CO2 gene.[1] Cytochrome c oxidase subunit II, abbreviated COXII, COX2, COII, or MT-CO2, is the second subunit of cytochrome c oxidase. StructureThe MT-CO2 gene is located on the p arm of mitochondrial DNA at position 12 and it spans 683 base pairs.[1] The MT-CO2 gene produces a 25.6 kDa protein composed of 227 amino acids.[2][3] MT-CO2 is a subunit of the enzyme Cytochrome c oxidase ({{EC number|1.9.3.1}})[4][5] (Complex IV), an oligomeric enzymatic complex of the mitochondrial respiratory chain involved in the transfer of electrons from cytochrome c to oxygen. In eukaryotes this enzyme complex is located in the mitochondrial inner membrane; in aerobic prokaryotes it is found in the plasma membrane. The enzyme complex consists of 3-4 subunits (prokaryotes) to up to 13 polypeptides (mammals). The N-terminal domain of cytochrome C oxidase contains two transmembrane alpha-helices.[5][4] The structure of MT-CO2 is known to contain one redox center and a binuclear copper A center (CuA). The CuA is located in a conserved cysteine loop at 196 and 200 amino acid positions and conserved histidine at 204. Several bacterial MT-CO2 have a C-terminal extension that contains a covalently bound haem c.[6][7] FunctionThe MT-CO2 gene encodes for the second subunit of cytochrome c oxidase (complex IV), a component of the mitochondrial respiratory chain that catalyzes the reduction of oxygen to water. MT-CO2 is one of the three subunits which are responsible for the formation of the functional core of the cytochrome c oxidase. MT-CO2 plays an essential role in the transfer of electrons from cytochrome c to the bimetallic center of the catalytic subunit 1 by utilizing its binuclear copper A center. It contains two adjacent transmembrane regions in its N-terminus and the major part of the protein is exposed to the periplasmic or to the mitochondrial intermembrane space, respectively. MT-CO2 provides the substrate-binding site and contains the binuclear copper A center, probably the primary acceptor in cytochrome c oxidase.[8][9][1] Clinical significanceMitochondrial complex IV deficiencyVariants of MT-CO2 have been associated with the mitochonrdial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain that catalyzes the oxidation of cytochrome c utilizing molecular oxygen.[10] The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation.[11] Mutations of MT-CO2 is also known to cause Leigh's disease, which may be caused by an abnormality or deficiency of cytochrome oxidase.[5][4] A wide range of symptoms have been found in patients with pathogenic mutations in the MT-CO2 gene with the mitochonrdial Complex IV deficiency. A deletion mutation of a single nucleotide (7630delT) in the gene has been found to cause symptoms of reversible aphasia, right hemiparesis, hemianopsia, exercise intolerance, progressive mental impairment, and short stature.[12] Furthermore, a patient with a nonsense mutation (7896G>A) of the gene resulted in phenotypes such as short stature, low weight, microcephaly, skin abnormalities, severe hypotonia, and normal reflexes.[13] A novel heteroplasmic mutation (7587T>C) which altered the initiation codon of the MT-CO2 gene in patients have shown clinical manifestations such as progressive gait ataxia, cognitive impairment, bilateral optic atrophy, pigmentary retinopathy, a decrease in color vision, and mild distal-muscle wasting.[14] OthersJuvenile myopathy, encephalopathy, lactic acidosis, and stroke have also been associated with mutations in the MT-CO2 gene.[1] InteractionsMT-CO2 is known to interact with cytochrome c by the utilization of a lysine ring around the carboxyl containing heme edge of cytochrome c in MT-CO2, including glutamate 129, aspartate 132, and glutamate 19. References1. ^1 2 3 {{cite web | title = Entrez Gene: COX2 cytochrome c oxidase subunit II| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4513| access-date = }}{{PD-notice}} {{clear}}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 = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }} 3. ^{{cite web | url = https://amino.heartproteome.org/web/protein/P00403 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Cytochrome c oxidase subunit 2 }} 4. ^1 2 {{cite journal | vauthors = Capaldi RA, Malatesta F, Darley-Usmar VM | title = Structure of cytochrome c oxidase | journal = Biochimica et Biophysica Acta | volume = 726 | issue = 2 | pages = 135–48 | date = July 1983 | pmid = 6307356 | doi = 10.1016/0304-4173(83)90003-4 }} 5. ^1 2 {{cite journal | vauthors = García-Horsman JA, Barquera B, Rumbley J, Ma J, Gennis RB | title = The superfamily of heme-copper respiratory oxidases | journal = Journal of Bacteriology | volume = 176 | issue = 18 | pages = 5587–600 | date = September 1994 | pmid = 8083153 | pmc = 196760 | doi = }} 6. ^{{cite journal | vauthors = Capaldi RA | title = Structure and function of cytochrome c oxidase | journal = Annual Review of Biochemistry | volume = 59 | pages = 569–96 | date = 1990 | pmid = 2165384 | doi = 10.1146/annurev.bi.59.070190.003033 }} 7. ^{{cite journal | vauthors = Hill BC | title = The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen | journal = Journal of Bioenergetics and Biomembranes | volume = 25 | issue = 2 | pages = 115–20 | date = April 1993 | pmid = 8389744 }} 8. ^ {{Cite web|url=https://www.uniprot.org/uniprot/P00403|title= MT-CO2 - Cytochrome c oxidase subunit 2 - Homo sapiens (Human) - MT-CO2 gene & protein|access-date=2018-08-07}}{{CC-notice|cc=by4 | url=https://www.uniprot.org/uniprot/Q9Y2R0 | work = UniProt }} 9. ^{{cite journal | vauthors = | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158-D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }} 10. ^{{cite journal | vauthors = Ostergaard E, Weraarpachai W, Ravn K, Born AP, Jønson L, Duno M, Wibrand F, Shoubridge EA, Vissing J | title = Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature | journal = Journal of Medical Genetics | volume = 52 | issue = 3 | pages = 203–7 | date = March 2015 | pmid = 25604084 | doi = 10.1136/jmedgenet-2014-102914 }} 11. ^{{cite web |title=Mitochondrial complex IV deficiency |url=https://www.uniprot.org/diseases/DI-01469 |website=www.uniprot.org |language=en}} 12. ^{{cite journal | vauthors = Rossmanith W, Freilinger M, Roka J, Raffelsberger T, Moser-Thier K, Prayer D, Bernert G, Bittner RE | title = Isolated cytochrome c oxidase deficiency as a cause of MELAS | journal = Journal of Medical Genetics | volume = 45 | issue = 2 | pages = 117–21 | date = February 2008 | pmid = 18245391 | doi = 10.1136/jmg.2007.052076 }} 13. ^{{cite journal | vauthors = Campos Y, García-Redondo A, Fernández-Moreno MA, Martínez-Pardo M, Goda G, Rubio JC, Martín MA, del Hoyo P, Cabello A, Bornstein B, Garesse R, Arenas J | title = Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene | journal = Annals of Neurology | volume = 50 | issue = 3 | pages = 409–13 | date = September 2001 | pmid = 11558799 }} 14. ^{{cite journal | vauthors = Clark KM, Taylor RW, Johnson MA, Chinnery PF, Chrzanowska-Lightowlers ZM, Andrews RM, Nelson IP, Wood NW, Lamont PJ, Hanna MG, Lightowlers RN, Turnbull DM | title = An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy | journal = American Journal of Human Genetics | volume = 64 | issue = 5 | pages = 1330–9 | date = May 1999 | pmid = 10205264 | doi = 10.1086/302361 }} Further reading{{refbegin | 2}}
4 : Protein domains|Protein families|Transmembrane proteins|Human mitochondrial genes |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。