Wikipedia

Cytochrome c oxidase subunit 2

(Redirected from COII)
"COX2" redirects here. For the cyclooxygenase isoenzyme, see Cyclooxygenase-2.

Cytochrome c oxidase II is a protein in eukaryotes that is encoded by the MT-CO2 gene.[5] 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.

COX2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCOX2, mitochondrially encoded cytochrome c oxidase II, COII, MTCO2, Cytochrome c oxidase subunit II, CO II
External IDsOMIM: 516040; MGI: 102503; HomoloGene: 5017; GeneCards: COX2; OMA:COX2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4513

17709

Ensembl

ENSG00000198712

ENSMUSG00000064354

UniProt

P00403

P00405

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

NP_904331

Location (UCSC)Chr M: 0.01 – 0.01 MbChr M: 0.01 – 0.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Location of the MT-CO2 gene in the human mitochondrial genome. MT-CO2 is one of the three cytochrome c oxidase subunit mitochondrial genes (orange boxes).
Cytochrome c oxidase subunit II, transmembrane domain
Bacterial cytochrome c oxidase complex. Subunit II indicated by blue.
Identifiers
SymbolCOX2_TM
PfamPF02790
InterProIPR011759
PROSITEPDOC00075
SCOP21occ / SCOPe / SUPFAM
TCDB3.D.4
OPM superfamily4
OPM protein1v55
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Cytochrome C oxidase subunit II, periplasmic domain
Identifiers
SymbolCOX2
PfamPF00116
InterProIPR002429
CDDcd13912
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Structure

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In humans, the MT-CO2 gene is located on the p arm of mitochondrial DNA at position 12 and it spans 683 base pairs.[5] The MT-CO2 gene produces a 25.6 kDa protein composed of 227 amino acids.[6][7] MT-CO2 is a subunit of the enzyme Cytochrome c oxidase (EC 1.9.3.1)[8][9] (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.[9][8] 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.[10][11]

Function

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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.[12][13][5]

Clinical significance

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Mitochondrial complex IV deficiency

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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.[14] 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 disability, delayed motor development and mental retardation.[15] Mutations of MT-CO2 is also known to cause Leigh's disease, which may be caused by an abnormality or deficiency of cytochrome oxidase.[9][8]

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.[16] 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.[17] 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.[18]

Others

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Juvenile myopathy, encephalopathy, lactic acidosis, and stroke have also been associated with mutations in the MT-CO2 gene.[5]

Interactions

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000198712 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000064354 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d "Entrez Gene: COX2 cytochrome c oxidase subunit II".  This article incorporates text from this source, which is in the public domain.
  6. ^ 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 (October 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.
  7. ^ "Cytochrome c oxidase subunit 2". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).[permanent dead link]
  8. ^ a b c Capaldi RA, Malatesta F, Darley-Usmar VM (July 1983). "Structure of cytochrome c oxidase". Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics. 726 (2): 135–48. doi:10.1016/0304-4173(83)90003-4. PMID 6307356.
  9. ^ a b c García-Horsman JA, Barquera B, Rumbley J, Ma J, Gennis RB (September 1994). "The superfamily of heme-copper respiratory oxidases". Journal of Bacteriology. 176 (18): 5587–600. doi:10.1128/jb.176.18.5587-5600.1994. PMC 196760. PMID 8083153.
  10. ^ Capaldi RA (1990). "Structure and function of cytochrome c oxidase". Annual Review of Biochemistry. 59: 569–96. doi:10.1146/annurev.bi.59.070190.003033. PMID 2165384.
  11. ^ Hill BC (April 1993). "The sequence of electron carriers in the reaction of cytochrome c oxidase with oxygen". Journal of Bioenergetics and Biomembranes. 25 (2): 115–20. doi:10.1007/bf00762853. PMID 8389744. S2CID 45975377.
  12. ^ "MT-CO2 - Cytochrome c oxidase subunit 2 - Homo sapiens (Human) - MT-CO2 gene & protein". Retrieved 2018-08-07.  This article incorporates text available under the CC BY 4.0 license.
  13. ^ "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  14. ^ Ostergaard E, Weraarpachai W, Ravn K, Born AP, Jønson L, Duno M, Wibrand F, Shoubridge EA, Vissing J (March 2015). "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. doi:10.1136/jmedgenet-2014-102914. PMID 25604084. S2CID 43018915.
  15. ^ "Mitochondrial complex IV deficiency". www.uniprot.org.
  16. ^ Rossmanith W, Freilinger M, Roka J, Raffelsberger T, Moser-Thier K, Prayer D, Bernert G, Bittner RE (February 2008). "Isolated cytochrome c oxidase deficiency as a cause of MELAS". Journal of Medical Genetics. 45 (2): 117–21. doi:10.1136/jmg.2007.052076. PMC 3027970. PMID 18245391.
  17. ^ 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 (September 2001). "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. doi:10.1002/ana.1141. PMID 11558799. S2CID 23891106.
  18. ^ 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 (May 1999). "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. doi:10.1086/302361. PMC 1377869. PMID 10205264.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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