COX20

Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene. This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.[1]

Structure

The COX20 gene is located on the q arm of chromosome 1 at position 44 and it spans 9,757 base pairs.[1] The COX20 gene produces a 13.3 kDa protein composed of 118 amino acids.[2][3] It contains two transmembrane helices and localizes to the mitochondrial membrane.[1]

Function

The COX20 gene encodes for a protein required for the assembly of cytochrome c oxidase (complex IV). Complex IV is the terminal complex of the mitochondrial respiratory chain which is required for catalyzing the oxidation of cytochrome c by molecular oxygen.[4] COX20 is known to act as a chaperone protein during the early stages of COX2 (cytochrome c oxidase subunit II) maturation which leads to the stabilization of the protein. By presenting COX2 to the metallochaperones SCO1 and SCO2, they help facilitate the incorporation of the mature COX2 into the complex IV holoenzyme assembly.[4][5][6] However, it has been known that COX20 has no influence on transcription or translation of COX2 or any other genes.[4] The knockdown of the protein COX20 has been shown to result in reduced respiratory capacity and the accumulation of respiratory chain intermediates.[7]

Clinical significance

Variants of COX20 have been associated with the mitochondrial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen.[8] 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.[9][5][6] A homozygous mutation of c.154A-C in the COX20 gene has been found to result in reduced COX20, cytochrome c oxidase, and decreased activity.[4] Other mutations have included a homozygous T52P.[10]

Interactions

COX20 has co-complex interactions with proteins such as TMEM177, COX2, SCO1, COA6, and others in a COX2 and COX18 dependent manner.[11][5][6]

References
  1. "Entrez Gene: Cytochrome c oxidase assembly factor COX20". Retrieved 2018-08-08. This article incorporates text from this source, which is in the public domain.
  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.
  3. "Cytochrome c oxidase protein 20 homolog". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-09. Retrieved 2018-08-08.
  4. Szklarczyk R, Wanschers BF, Nijtmans LG, Rodenburg RJ, Zschocke J, Dikow N, van den Brand MA, Hendriks-Franssen MG, Gilissen C, Veltman JA, Nooteboom M, Koopman WJ, Willems PH, Smeitink JA, Huynen MA, van den Heuvel LP (February 2013). "A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c oxidase assembly and is associated with ataxia and muscle hypotonia". Hum. Mol. Genet. 22 (4): 656–67. doi:10.1093/hmg/dds473. PMID 23125284.
  5. "Cytochrome c oxidase assembly protein COX20, mitochondrial". Retrieved 2018-08-07. This article incorporates text available under the CC BY 4.0 license.
  6. "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  7. Bourens M, Boulet A, Leary SC, Barrientos A (June 2014). "Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase". Hum. Mol. Genet. 23 (11): 2901–13. doi:10.1093/hmg/ddu003. PMC 4014192. PMID 24403053.
  8. 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.
  9. "Mitochondrial complex IV deficiency". www.uniprot.org.
  10. Doss S, Lohmann K, Seibler P, Arns B, Klopstock T, Zühlke C, Freimann K, Winkler S, Lohnau T, Drungowski M, Nürnberg P, Wiegers K, Lohmann E, Naz S, Kasten M, Bohner G, Ramirez A, Endres M, Klein C (January 2014). "Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation". J. Neurol. 261 (1): 207–12. doi:10.1007/s00415-013-7177-7. PMID 24202787.
  11. Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I, Sasarman F, Weraarpachai W, Shoubridge EA, Warscheid B, Rehling P (December 2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation". Cell. 151 (7): 1528–41. doi:10.1016/j.cell.2012.11.053. PMID 23260140.

Further reading

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

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