View source for SCO2

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{For|sCO<sub>2</sub>, the phase of carbon dioxide|supercritical carbon dioxide}}
{{Infobox_gene}}
'''SCO2 cytochrome c oxidase assembly''' (also known as '''SCO2 homolog, mitochondrial''' and '''SCO cytochrome oxidase deficient homolog 2''') is a [[protein]] that in humans is encoded by the ''SCO2'' [[gene]].<ref name="pmid10218584">{{cite journal | vauthors = Paret C, Ostermann K, Krause-Buchholz U, Rentzsch A, Rödel G | title = Human members of the SCO1 gene family: complementation analysis in yeast and intracellular localization | journal = FEBS Letters | volume = 447 | issue = 1 | pages = 65–70 | date = March 1999 | pmid = 10218584 | doi = 10.1016/S0014-5793(99)00266-5 | doi-access = free }}</ref><ref name="pmid16091356">{{cite journal | vauthors = Horng YC, Leary SC, Cobine PA, Young FB, George GN, Shoubridge EA, Winge DR | title = Human Sco1 and Sco2 function as copper-binding proteins | journal = The Journal of Biological Chemistry | volume = 280 | issue = 40 | pages = 34113–22 | date = October 2005 | pmid = 16091356 | doi = 10.1074/jbc.M506801200 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SCO2 SCO2 cytochrome c oxidase assembly protein [ ''Homo sapiens'' (human) ] | url = https://www.ncbi.nlm.nih.gov/gene/9997 }}</ref> The encoded protein is one of the [[Cytochrome c oxidase|cytochrome c oxidase (COX)]](Complex IV) assembly factors. Human [[Cytochrome c oxidase|COX]] is a multimeric [[protein complex]] that requires several assembly factors. [[Cytochrome c oxidase|Cytochrome c oxidase (COX)]] [[catalysis|catalyzes]] the transfer of electrons from [[cytochrome c]] to [[molecular oxygen]], which helps to maintain the [[proton gradient]] across the [[inner mitochondrial membrane]] that is necessary for aerobic [[Adenosine triphosphate|ATP]] production. The encoded protein is a [[chaperone (protein)|metallochaperone]] that is involved in the biogenesis of [[cytochrome c oxidase subunit II]]. Mutations in this gene are associated with fatal infantile encephalocardiomyopathy and [[myopia]] 6.<ref name = entrez />

== Structure ==
The ''SCO2'' gene is located on the [[Locus (genetics)|q arm]] of [[chromosome 22]] at position 13.33 and it spans 2,871 base pairs.<ref name = entrez /> The ''SCO2'' gene produces a 15.1 kDa protein composed of 136 [[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 = October 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/C9JBU1 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Protein SCO2 homolog, mitochondrial }}{{Dead link|date=July 2025 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> The protein contains an [[N-terminal]] mitochondrial targeting presequence of 41 [[amino acids]], and shares identity with the [[yeast]] protein in regions between [[glycine]]-102 and [[glycine]]-242 in human SCO2.<ref>{{cite journal | vauthors = Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA | title = Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene | journal = Nature Genetics | volume = 23 | issue = 3 | pages = 333–7 | date = November 1999 | pmid = 10545952 | doi = 10.1038/15513 | s2cid = 23387553 }}</ref> SCO2 is a subunit of the enzyme [[Cytochrome c oxidase|Mammalian cytochrome c oxidase (COX)]](Complex IV).<ref name="entrez"/>

== Function ==
The ''SCO2'' gene encodes for a [[protein]] essential for the assembly and function of [[Cytochrome c oxidase|Mammalian cytochrome c oxidase (COX)]](Complex IV) of the [[mitochondrial respiratory chain]]. SCO2 acts as a [[Chaperone (protein)|metallochaperone]] involved in the [[biogenesis]] of [[cytochrome c oxidase subunit II]], an essential subunit of [[Cytochrome c oxidase|Complex IV]] which transfers the electrons from [[cytochrome c]] to the bimetallic center of the [[Cytochrome c oxidase subunit I|catalytic subunit 1]] via its binuclear copper A center.<ref name = "hehe">{{Cite web|url=https://www.uniprot.org/uniprot/P00403|title= MT-CO2 - Cytochrome c oxidase subunit 2 - Homo sapiens (Human) - MT-CO2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-07-31}}{{CC-notice|cc=by4 | url=www.uniprot.org | author(s)= UniProt }}</ref> The biogenesis involves the transport of copper to the Cu(A) site on the [[cytochrome c oxidase subunit II]] leading to the proper synthesis and maturation of the subunit. In addition, SCO2 acts as a [[thiol]]-[[disulfide]] [[oxidoreductase]] to regulate the redox state of the [[cystein]]es in [[SCO1]] during maturation of the [[cytochrome c oxidase subunit II]]. The maturation and synthesis of [[cytochrome c oxidase subunit II]] is required for the function of [[Cytochrome c oxidase|Mammalian cytochrome c oxidase (COX)]](Complex IV).<ref name="uniprot0">{{Cite web|url=https://www.uniprot.org/uniprot/O43819|title= SCO2 - Protein SCO2 homolog, mitochondrial precursor - Homo sapiens (Human) - SCO2 gene & protein|website=www.uniprot.org|language=en|access-date=2018-07-31}}{{CC-notice|cc=by4 | url=www.uniprot.org | author(s)= UniProt }}</ref><ref name="uniprot2">{{cite journal | 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>[[Cytochrome c oxidase|Complex IV]], a multimeric [[protein complex]] that requires several assembly factors, [[catalysis|catalyzes]] the transfer of reducing equivalents from [[cytochrome c]] to molecular [[oxygen]] and pumps [[protons]] across the [[inner mitochondrial membrane]].<ref name="entrez" />

==Clinical significance==
Mutations in ''SCO2'' that alter the regulation of [[copper]] and [[oxygen]] have been found to be associated with fatal infantile Cardioencephalomyopathy due to cytochrome c oxidase deficiency 1 (CEMCOX1), [[Myopia|Myopia 6]] (MYP6), and [[Leigh syndrome]] (LS).<ref>

{{cite journal | vauthors = Jaksch M, Paret C, Stucka R, Horn N, Müller-Höcker J, Horvath R, Trepesch N, Stecker G, Freisinger P, Thirion C, Müller J, Lunkwitz R, Rödel G, Shoubridge EA, Lochmüller H | title = Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts | journal = Human Molecular Genetics | volume = 10 | issue = 26 | pages = 3025–35 | date = December 2001 | pmid = 11751685 | doi = 10.1093/hmg/10.26.3025 | doi-access = free }}

</ref><ref name="uniprot0"/> CEMCOX1 is characterized by disorders characterized by [[hypotonia]], [[Developmental disability|developmental delay]], [[hypertrophic cardiomyopathy]], [[lactic acidosis]], [[gliosis]], neuronal loss in [[basal ganglia]], [[brainstem]] and [[spinal cord]], and [[cytochrome c oxidase]] deficiency. [[Myopia|Myopia 6]] is characterized by a [[refraction|refractive]] error of the eye, in which parallel rays from a distant object come to focus in front of the [[retina]], vision being better for near objects than for far. Lastly, [[leigh syndrome]] is an early-onset progressive [[Neurodegeneration|neurodegenerative disorder]] characterized by the presence of focal, bilateral [[lesion]]s in one or more areas of the [[central nervous system]] including the [[brainstem]], [[thalamus]], [[basal ganglia]], [[cerebellum]] and [[spinal cord]]. Clinical manifestations may include [[psychomotor retardation]], [[hypotonia]], [[ataxia]], weakness, [[vision loss]], [[eye movement]] abnormalities, [[seizures]], and [[dysphagia]].<ref name="uniprot0"/> A pathogenic mutation of G1541A in a patient has shown strong evidence in neonatal [[hypotonia]] with an SMA 1 phenotype, and has been found to result in less [[Cytochrome c oxidase|COX]] deficiencies.<ref>{{cite journal | vauthors = Tarnopolsky MA, Bourgeois JM, Fu MH, Kataeva G, Shah J, Simon DK, Mahoney D, Johns D, MacKay N, Robinson BH | title = Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype | journal = American Journal of Medical Genetics. Part A | volume = 125A | issue = 3 | pages = 310–4 | date = March 2004 | pmid = 14994243 | doi = 10.1002/ajmg.a.20466 | s2cid = 24732177 }}</ref> A mutation of 1602T>G has been found to result in rapidly progressive disease [[phenotypes]].<ref>{{cite journal | vauthors = Knuf M, Faber J, Huth RG, Freisinger P, Zepp F, Kampmann C | title = Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy | journal = Acta Paediatrica | volume = 96 | issue = 1 | pages = 130–2 | date = January 2007 | pmid = 17187620 | doi = 10.1111/j.1651-2227.2007.00008.x | s2cid = 20422657 }}</ref> Other pathogenic mutations have included a [[missense mutation]] of E140K, a [[nonsense mutation]] Q53X, and a 1541G > A mutation which resulted in a severe protein instability.<ref>{{cite journal | vauthors = Salviati L, Sacconi S, Rasalan MM, Kronn DF, Braun A, Canoll P, Davidson M, Shanske S, Bonilla E, Hays AP, Schon EA, DiMauro S | title = Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease | journal = Archives of Neurology | volume = 59 | issue = 5 | pages = 862–5 | date = May 2002 | pmid = 12020273 | doi = 10.1001/archneur.59.5.862 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tay SK, Shanske S, Kaplan P, DiMauro S | title = Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality | journal = Archives of Neurology | volume = 61 | issue = 6 | pages = 950–2 | date = June 2004 | pmid = 15210538 | doi = 10.1001/archneur.61.6.950 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Joost K, Rodenburg R, Piirsoo A, van den Heuvel B, Zordania R, Ounap K | title = A novel mutation in the SCO2 gene in a neonate with early-onset cardioencephalomyopathy | journal = Pediatric Neurology | volume = 42 | issue = 3 | pages = 227–30 | date = March 2010 | pmid = 20159436 | doi = 10.1016/j.pediatrneurol.2009.10.004 }}</ref>

== Interactions ==

In addition to co-complex interactions, SCO2 has been found to interact with [[COA6]], [[THEM177]] in a [[COX20]]-dependent manner, [[COX20]], [[COX16]], [[SCO1]], and others.<ref name="uniprot0"/><ref>
{{cite journal | vauthors = Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H | title = IntAct--open source resource for molecular interaction data | journal = Nucleic Acids Research | volume = 35 | issue = Database issue | pages = D561–5 | date = January 2007 | pmid = 17145710 | pmc = 1751531 | doi = 10.1093/nar/gkl958 }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Jaksch M, Ogilvie I, Yao J, Kortenhaus G, Bresser HG, Gerbitz KD, Shoubridge EA | title = Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency | journal = Human Molecular Genetics | volume = 9 | issue = 5 | pages = 795–801 | date = March 2000 | pmid = 10749987 | doi = 10.1093/hmg/9.5.795 | doi-access = free }}
* {{cite journal | vauthors = Jaksch M, Horvath R, Horn N, Auer DP, Macmillan C, Peters J, Gerbitz KD, Kraegeloh-Mann I, Muntau A, Karcagi V, Kalmanchey R, Lochmuller H, Shoubridge EA, Freisinger P | title = Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy | journal = Neurology | volume = 57 | issue = 8 | pages = 1440–6 | date = October 2001 | pmid = 11673586 | doi = 10.1212/wnl.57.8.1440 | s2cid = 24920023 }}
* {{cite journal | vauthors = Jaksch M, Paret C, Stucka R, Horn N, Müller-Höcker J, Horvath R, Trepesch N, Stecker G, Freisinger P, Thirion C, Müller J, Lunkwitz R, Rödel G, Shoubridge EA, Lochmüller H | title = Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts | journal = Human Molecular Genetics | volume = 10 | issue = 26 | pages = 3025–35 | date = December 2001 | pmid = 11751685 | doi = 10.1093/hmg/10.26.3025 | doi-access = free }}
* {{cite journal | vauthors = Salviati L, Hernandez-Rosa E, Walker WF, Sacconi S, DiMauro S, Schon EA, Davidson MM | title = Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations | journal = The Biochemical Journal | volume = 363 | issue = Pt 2 | pages = 321–7 | date = April 2002 | pmid = 11931660 | pmc = 1222481 | doi = 10.1042/0264-6021:3630321 }}
* {{cite journal | vauthors = Collins JE, Goward ME, Cole CG, Smink LJ, Huckle EJ, Knowles S, Bye JM, Beare DM, Dunham I | title = Reevaluating human gene annotation: a second-generation analysis of chromosome 22 | journal = Genome Research | volume = 13 | issue = 1 | pages = 27–36 | date = January 2003 | pmid = 12529303 | pmc = 430954 | doi = 10.1101/gr.695703 }}
* {{cite journal | vauthors = Sacconi S, Salviati L, Sue CM, Shanske S, Davidson MM, Bonilla E, Naini AB, De Vivo DC, DiMauro S | title = Mutation screening in patients with isolated cytochrome c oxidase deficiency | journal = Pediatric Research | volume = 53 | issue = 2 | pages = 224–30 | date = February 2003 | pmid = 12538779 | doi = 10.1203/01.PDR.0000048100.91730.6A | hdl = 11577/1368344 | s2cid = 12496207 | hdl-access = free }}
* {{cite journal | vauthors = Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW | title = Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation | journal = Nature Biotechnology | volume = 22 | issue = 6 | pages = 707–16 | date = June 2004 | pmid = 15146197 | doi = 10.1038/nbt971 | s2cid = 27764390 }}
* {{cite journal | vauthors = Leary SC, Kaufman BA, Pellecchia G, Guercin GH, Mattman A, Jaksch M, Shoubridge EA | title = Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase | journal = Human Molecular Genetics | volume = 13 | issue = 17 | pages = 1839–48 | date = September 2004 | pmid = 15229189 | doi = 10.1093/hmg/ddh197 | doi-access = free }}
* {{cite journal | vauthors = Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I | title = A genome annotation-driven approach to cloning the human ORFeome | journal = Genome Biology | volume = 5 | issue = 10 | pages = R84 | year = 2005 | pmid = 15461802 | pmc = 545604 | doi = 10.1186/gb-2004-5-10-r84 | doi-access = free }}
* {{cite journal | vauthors = Stiburek L, Vesela K, Hansikova H, Pecina P, Tesarova M, Cerna L, Houstek J, Zeman J | title = Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1 | journal = The Biochemical Journal | volume = 392 | issue = Pt 3 | pages = 625–32 | date = December 2005 | pmid = 16083427 | pmc = 1316303 | doi = 10.1042/BJ20050807 }}
* {{cite journal | vauthors = Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM | title = p53 regulates mitochondrial respiration | journal = Science | volume = 312 | issue = 5780 | pages = 1650–3 | date = June 2006 | pmid = 16728594 | doi = 10.1126/science.1126863 | bibcode = 2006Sci...312.1650M | s2cid = 36668814 }}
* {{cite journal | vauthors = Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA | title = The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis | journal = Cell Metabolism | volume = 5 | issue = 1 | pages = 9–20 | date = January 2007 | pmid = 17189203 | doi = 10.1016/j.cmet.2006.12.001 | doi-access = free }}
* {{cite journal | vauthors = Banci L, Bertini I, Ciofi-Baffoni S, Gerothanassis IP, Leontari I, Martinelli M, Wang S | title = A structural characterization of human SCO2 | journal = Structure | volume = 15 | issue = 9 | pages = 1132–40 | date = September 2007 | pmid = 17850752 | doi = 10.1016/j.str.2007.07.011 | doi-access = free }}
{{refend}}

== External links ==

* {{UCSC genome browser|SCO2}}
* {{UCSC gene details|SCO2}}