Biology:Cytochrome c oxidase subunit 2
 Generic protein structure example |
| Cytochrome c oxidase subunit II, transmembrane domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Bacterial cytochrome c oxidase complex. Subunit II indicated by blue. | |||||||||
| Identifiers | |||||||||
| Symbol | COX2_TM | ||||||||
| Pfam | PF02790 | ||||||||
| InterPro | IPR011759 | ||||||||
| PROSITE | PDOC00075 | ||||||||
| SCOP2 | 1occ / SCOPe / SUPFAM | ||||||||
| TCDB | 3.D.4 | ||||||||
| OPM superfamily | 4 | ||||||||
| OPM protein | 1v55 | ||||||||
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| Cytochrome C oxidase subunit II, periplasmic domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | COX2 | ||||||||
| Pfam | PF00116 | ||||||||
| InterPro | IPR002429 | ||||||||
| CDD | cd13912 | ||||||||
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Cytochrome c oxidase II is a protein in eukaryotes that 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. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits (MT-CO1, MT-CO2, MT-CO3) of respiratory complex IV.
Structure
In humans, the 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 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]
Function
The 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 significance
Mitochondrial complex IV deficiency
Variants of MT-CO2 have been associated with the mitochondrial 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 mitochondrial 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]
Others
Juvenile myopathy, encephalopathy, lactic acidosis, and stroke have also been associated with mutations in the MT-CO2 gene.[1]
Interactions
MT-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.
References
- ↑ 1.0 1.1 1.2 1.3 "Entrez Gene: COX2 cytochrome c oxidase subunit II". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4513.
This article incorporates text from this source, which is in the public domain.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "Cytochrome c oxidase subunit 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/P00403.[yes|permanent dead link|dead link}}]
- ↑ 4.0 4.1 4.2 "Structure of cytochrome c oxidase". Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics 726 (2): 135–48. July 1983. doi:10.1016/0304-4173(83)90003-4. PMID 6307356.
- ↑ 5.0 5.1 5.2 "The superfamily of heme-copper respiratory oxidases". Journal of Bacteriology 176 (18): 5587–600. September 1994. doi:10.1128/jb.176.18.5587-5600.1994. PMID 8083153.
- ↑ "Structure and function of cytochrome c oxidase". Annual Review of Biochemistry 59: 569–96. 1990. doi:10.1146/annurev.bi.59.070190.003033. PMID 2165384.
- ↑ "The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen". Journal of Bioenergetics and Biomembranes 25 (2): 115–20. April 1993. doi:10.1007/bf00762853. PMID 8389744.
- ↑
"MT-CO2 - Cytochrome c oxidase subunit 2 - Homo sapiens (Human) - MT-CO2 gene & protein". https://www.uniprot.org/uniprot/P00403.
This article incorporates text available under the CC BY 4.0 license.
- ↑ "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622.
- ↑ "Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature". Journal of Medical Genetics 52 (3): 203–7. March 2015. doi:10.1136/jmedgenet-2014-102914. PMID 25604084.
- ↑ "Mitochondrial complex IV deficiency" (in en). https://www.uniprot.org/diseases/DI-01469.
- ↑ "Isolated cytochrome c oxidase deficiency as a cause of MELAS". Journal of Medical Genetics 45 (2): 117–21. February 2008. doi:10.1136/jmg.2007.052076. PMID 18245391.
- ↑ "Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene". Annals of Neurology 50 (3): 409–13. September 2001. doi:10.1002/ana.1141. PMID 11558799.
- ↑ "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". American Journal of Human Genetics 64 (5): 1330–9. May 1999. doi:10.1086/302361. PMID 10205264.
Further reading
- "Harvesting the fruit of the human mtDNA tree". Trends in Genetics 22 (6): 339–45. June 2006. doi:10.1016/j.tig.2006.04.001. PMID 16678300.
- "A different genetic code in human mitochondria". Nature 282 (5735): 189–94. November 1979. doi:10.1038/282189a0. PMID 226894. Bibcode: 1979Natur.282..189B.
- "Dinucleotide repeat in the human mitochondrial D-loop". Human Molecular Genetics 1 (2): 140. May 1992. doi:10.1093/hmg/1.2.140-a. PMID 1301157.
- "Differentiation of HT-29 human colonic adenocarcinoma cells correlates with increased expression of mitochondrial RNA: effects of trehalose on cell growth and maturation". Cancer Research 52 (13): 3718–25. July 1992. PMID 1377597.
- "Normal variants of human mitochondrial DNA and translation products: the building of a reference data base". Human Genetics 88 (2): 139–45. December 1991. doi:10.1007/bf00206061. PMID 1757091.
- "Replication-competent human mitochondrial DNA lacking the heavy-strand promoter region". Molecular and Cellular Biology 11 (3): 1631–7. March 1991. doi:10.1128/MCB.11.3.1631. PMID 1996112.
- "Nucleotide sequence of human mitochondrial cytochrome c oxidase II cDNA". Nucleic Acids Research 17 (16): 6734. August 1989. doi:10.1093/nar/17.16.6734. PMID 2550900.
- "Seven unidentified reading frames of human mitochondrial DNA encode subunits of the respiratory chain NADH dehydrogenase". Cold Spring Harbor Symposia on Quantitative Biology 51 (1): 103–14. 1987. doi:10.1101/sqb.1986.051.01.013. PMID 3472707.
- "URF6, last unidentified reading frame of human mtDNA, codes for an NADH dehydrogenase subunit". Science 234 (4776): 614–8. October 1986. doi:10.1126/science.3764430. PMID 3764430. Bibcode: 1986Sci...234..614C.
- "Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase". Nature 314 (6012): 592–7. 1985. doi:10.1038/314592a0. PMID 3921850. Bibcode: 1985Natur.314..592C.
- "Sequence and organization of the human mitochondrial genome". Nature 290 (5806): 457–65. April 1981. doi:10.1038/290457a0. PMID 7219534. Bibcode: 1981Natur.290..457A.
- "Distinctive features of the 5'-terminal sequences of the human mitochondrial mRNAs". Nature 290 (5806): 465–70. April 1981. doi:10.1038/290465a0. PMID 7219535. Bibcode: 1981Natur.290..465M.
- "Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs". Proceedings of the National Academy of Sciences of the United States of America 92 (2): 532–6. January 1995. doi:10.1073/pnas.92.2.532. PMID 7530363. Bibcode: 1995PNAS...92..532H.
- "Mitochondrial COII sequences and modern human origins". Molecular Biology and Evolution 10 (6): 1115–35. November 1993. doi:10.1093/oxfordjournals.molbev.a040068. PMID 8277847.
- "Somatic mutations of the mitochondrial genome in human colorectal tumours". Nature Genetics 20 (3): 291–3. November 1998. doi:10.1038/3108. PMID 9806551.
- "The mechanisms of death of an erythroleukemic cell line by p53: involvement of the microtubule and mitochondria". Leukemia & Lymphoma 33 (1–2): 181–6. March 1999. doi:10.3109/10428199909093740. PMID 10194136.
- "Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA". Nature Genetics 23 (2): 147. October 1999. doi:10.1038/13779. PMID 10508508.
- "Mitochondrial genome variation and the origin of modern humans". Nature 408 (6813): 708–13. December 2000. doi:10.1038/35047064. PMID 11130070. Bibcode: 2000Natur.408..708I.
- "Phylogenetic network for European mtDNA". American Journal of Human Genetics 68 (6): 1475–84. June 2001. doi:10.1086/320591. PMID 11349229.
- "Major genomic mitochondrial lineages delineate early human expansions". BMC Genetics 2: 13. 2003. doi:10.1186/1471-2156-2-13. PMID 11553319.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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