View source for 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 [[Cellular respiration|respiratory pathway]]. [[Mutations]] in this gene can cause mitochondrial [[cytochrome c oxidase|complex IV]] deficiency. There are multiple [[pseudogenes]] for this gene. [[Alternative splicing]] results in multiple [[transcript variants]].<ref name="entrez">
{{cite web
| title = Entrez Gene: Cytochrome c oxidase assembly factor COX20
| url = http://www.ncbi.nlm.nih.gov/gene/116228
| accessdate = 2018-08-08
}}{{PD-notice}}</ref>

==Structure==
The ''COX20'' gene is located on the [[Locus (genetics)|q arm]] of [[chromosome 1]] at position 44 and it spans 9,757 base pairs.<ref name = entrez /> The ''COX20'' gene produces a 13.3 kDa protein composed of 118 [[amino acids]].<ref name=COPaKB>

{{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 }}

</ref><ref name="url_COPaKB">

{{cite web | url = https://amino.heartproteome.org/web/protein/Q5RI15 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Cytochrome c oxidase protein 20 homolog }}

</ref> It contains two [[Transmembrane domain|transmembrane helices]] and localizes to the [[mitochondrial membrane]].<ref name = entrez />

==Function==
The ''COX20'' gene encodes for a [[protein]] required for the assembly of [[cytochrome c oxidase]](complex IV). [[cytochrome c oxidase|Complex IV]] is the terminal complex of the [[mitochondrial respiratory chain]] which is required for [[catalysis|catalyzing]] the oxidation of [[cytochrome c]] by [[oxygen|molecular oxygen]].<ref name = "hello">{{cite journal |vauthors=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 |title=A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c oxidase assembly and is associated with ataxia and muscle hypotonia |journal=Hum. Mol. Genet. |volume=22 |issue=4 |pages=656–67 |date=February 2013 |pmid=23125284 |doi=10.1093/hmg/dds473 |url=}}</ref> COX20 is known to act as a [[chaperone (protein)|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 [[cytochrome c oxidase|complex IV]] holoenzyme assembly.<ref name = "hello"/><ref name="uniprot">

{{Cite web|url=https://www.uniprot.org/uniprot/Q5RI15|title= Cytochrome c oxidase assembly protein COX20, mitochondrial|access-date=2018-08-07}}{{CC-notice|cc=by4 | url=https://www.uniprot.org/uniprot/Q9Y2R0 | work = UniProt }}

</ref><ref name="uniprot1">

{{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 }}

</ref> However, it has been known that COX20 has no influence on [[Transcription (biology)|transcription]] or [[Translation (biology)|translation]] of [[COX2]] or any other genes.<ref name = "hello"/> The knockdown of the protein COX20 has been shown to result in reduced [[cellular respiration|respiratory capacity]] and the accumulation of respiratory chain intermediates]].<ref name = ":)">{{cite journal |vauthors=Bourens M, Boulet A, Leary SC, Barrientos A |title=Human COX20 cooperates with SCO1 and SCO2 to mature COX2 and promote the assembly of cytochrome c oxidase |journal=Hum. Mol. Genet. |volume=23 |issue=11 |pages=2901–13 |date=June 2014 |pmid=24403053 |pmc=4014192 |doi=10.1093/hmg/ddu003 |url=}}</ref>

==Clinical significance==
Variants of ''COX20'' have been associated with the [[mitochondria|mitochonrdial]] [[cytochrome c oxidase|Complex IV]] deficiency, a deficiency in an enzyme complex of the [[mitochondrial respiratory chain]] which catalyzes the oxidation of [[cytochrome c]] utilizing [[oxygen|molecular oxygen]].<ref name = "hi2">

{{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 }}

</ref> 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]].<ref>{{cite web |title=Mitochondrial complex IV deficiency |url=https://www.uniprot.org/diseases/DI-01469 |website=www.uniprot.org |language=en}}</ref><ref name="uniprot"/><ref name="uniprot1"/> 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.<ref name = "hello"/> Other mutations have included a homozygous T52P.<ref>{{cite journal |vauthors=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 |title=Recessive dystonia-ataxia syndrome in a Turkish family caused by a COX20 (FAM36A) mutation |journal=J. Neurol. |volume=261 |issue=1 |pages=207–12 |date=January 2014 |pmid=24202787 |doi=10.1007/s00415-013-7177-7 |url=}}</ref>

==Interactions==
COX20 has co-complex interactions with proteins such as [[TMEM177]], [[COX2]], [[SCO1]], [[COA6]], and others in a [[COX2]] and [[COX18]] dependent manner.<ref name = "hi">

{{cite journal | vauthors = Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I, Sasarman F, Weraarpachai W, Shoubridge EA, Warscheid B, Rehling P | title = MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation | journal = Cell | volume = 151 | issue = 7 | pages = 1528–41 | date = December 2012 | pmid = 23260140 | doi = 10.1016/j.cell.2012.11.053 }}</ref><ref name = "uniprot" /><ref name="uniprot1"/>

== References ==

{{reflist}}

== Further reading ==

{{refbegin | 2}}
*{{cite journal |vauthors=Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ |title=Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression |journal=PLoS ONE |volume=5 |issue=9 |pages=e12862 |date=September 2010 |pmid=20877624 |pmc=2943476 |doi=10.1371/journal.pone.0012862 |url=}}
*{{cite journal |vauthors=Thierry G, Bénéteau C, Pichon O, Flori E, Isidor B, Popelard F, Delrue MA, Duboscq-Bidot L, Thuresson AC, van Bon BW, Cailley D, Rooryck C, Paubel A, Metay C, Dusser A, Pasquier L, Béri M, Bonnet C, Jaillard S, Dubourg C, Tou B, Quéré MP, Soussi-Zander C, Toutain A, Lacombe D, Arveiler B, de Vries BB, Jonveaux P, David A, Le Caignec C |title=Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures |journal=Am. J. Med. Genet. A |volume=158A |issue=7 |pages=1633–40 |date=July 2012 |pmid=22678713 |doi=10.1002/ajmg.a.35423 |url=http://www.hal.inserm.fr/inserm-00706725/document}}

{{refend}}

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[[Category:Human proteins]]
[[Category:Genes on human chromosome 1]]