SCO2

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.[5][6][7] The encoded protein is one of the cytochrome c oxidase (COX)(Complex IV) assembly factors. Human COX is a multimeric protein complex that requires several assembly factors. Cytochrome c oxidase (COX) 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 ATP production. The encoded protein is a 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.[7]

For sCO2, the phase of carbon dioxide, see supercritical carbon dioxide.
SCO2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSCO2, CEMCOX1, MYP6, SCO1L, SCO2 cytochrome c oxidase assembly protein, cytochrome c oxidase assembly protein, PD-ECGF, TP, Gliostatin, TYMP, ECGF1, TdRPase, SCO cytochrome c oxidase assembly protein 2, synthesis of cytochrome C oxidase 2, MC4DN2
External IDsOMIM: 604272 MGI: 3818630 HomoloGene: 68444 GeneCards: SCO2
Orthologs
SpeciesHumanMouse
Entrez

9997

100126824

Ensembl

ENSG00000284194

ENSMUSG00000091780

UniProt

O43819

Q8VCL2

RefSeq (mRNA)

NM_005138
NM_001169109
NM_001169110
NM_001169111

NM_001111288

RefSeq (protein)

NP_001162580
NP_001162581
NP_001162582
NP_005129

NP_001104758

Location (UCSC)Chr 22: 50.52 – 50.53 MbChr 15: 89.26 – 89.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure

The SCO2 gene is located on the q arm of chromosome 22 at position 13.33 and it spans 2,871 base pairs.[7] The SCO2 gene produces a 15.1 kDa protein composed of 136 amino acids.[8][9] 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.[10] SCO2 is a subunit of the enzyme Mammalian cytochrome c oxidase (COX)(Complex IV).[7]

Function

The SCO2 gene encodes for a protein essential for the assembly and function of Mammalian cytochrome c oxidase (COX)(Complex IV) of the mitochondrial respiratory chain. SCO2 acts as a metallochaperone involved in the biogenesis of cytochrome c oxidase subunit II, an essential subunit of Complex IV which transfers the electrons from cytochrome c to the bimetallic center of the catalytic subunit 1 via its binuclear copper A center.[11] 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 cysteines 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 Mammalian cytochrome c oxidase (COX)(Complex IV).[12][13]Complex IV, a multimeric protein complex that requires several assembly factors, catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane.[7]

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 6 (MYP6), and Leigh syndrome (LS).[14][12] CEMCOX1 is characterized by disorders characterized by hypotonia, developmental delay, hypertrophic cardiomyopathy, lactic acidosis, gliosis, neuronal loss in basal ganglia, brainstem and spinal cord, and cytochrome c oxidase deficiency. Myopia 6 is characterized by a 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 neurodegenerative disorder characterized by the presence of focal, bilateral lesions 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.[12] 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 COX deficiencies.[15] A mutation of 1602T>G has been found to result in rapidly progressive disease phenotypes.[16] 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.[17][18][19]

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.[12][20]

References
  1. GRCh38: Ensembl release 89: ENSG00000284194 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000091780 - 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. Paret C, Ostermann K, Krause-Buchholz U, Rentzsch A, Rödel G (March 1999). "Human members of the SCO1 gene family: complementation analysis in yeast and intracellular localization". FEBS Letters. 447 (1): 65–70. doi:10.1016/S0014-5793(99)00266-5. PMID 10218584.
  6. Horng YC, Leary SC, Cobine PA, Young FB, George GN, Shoubridge EA, Winge DR (October 2005). "Human Sco1 and Sco2 function as copper-binding proteins". The Journal of Biological Chemistry. 280 (40): 34113–22. doi:10.1074/jbc.M506801200. PMID 16091356.
  7. "Entrez Gene: SCO2 SCO2 cytochrome c oxidase assembly protein [ Homo sapiens (human) ]".
  8. 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.
  9. "Protein SCO2 homolog, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  10. 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 (November 1999). "Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene". Nature Genetics. 23 (3): 333–7. doi:10.1038/15513. PMID 10545952. S2CID 23387553.
  11. "MT-CO2 - Cytochrome c oxidase subunit 2 - Homo sapiens (Human) - MT-CO2 gene & protein". www.uniprot.org. Retrieved 2018-07-31. This article incorporates [www.uniprot.org text] by UniProt available under the CC BY 4.0 license.
  12. "SCO2 - Protein SCO2 homolog, mitochondrial precursor - Homo sapiens (Human) - SCO2 gene & protein". www.uniprot.org. Retrieved 2018-07-31. This article incorporates [www.uniprot.org text] by UniProt 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. 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 (December 2001). "Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts". Human Molecular Genetics. 10 (26): 3025–35. doi:10.1093/hmg/10.26.3025. PMID 11751685.
  15. Tarnopolsky MA, Bourgeois JM, Fu MH, Kataeva G, Shah J, Simon DK, Mahoney D, Johns D, MacKay N, Robinson BH (March 2004). "Novel SCO2 mutation (G1521A) presenting as a spinal muscular atrophy type I phenotype". American Journal of Medical Genetics. Part A. 125A (3): 310–4. doi:10.1002/ajmg.a.20466. PMID 14994243. S2CID 24732177.
  16. Knuf M, Faber J, Huth RG, Freisinger P, Zepp F, Kampmann C (January 2007). "Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy". Acta Paediatrica. 96 (1): 130–2. doi:10.1111/j.1651-2227.2007.00008.x. PMID 17187620. S2CID 20422657.
  17. Salviati L, Sacconi S, Rasalan MM, Kronn DF, Braun A, Canoll P, Davidson M, Shanske S, Bonilla E, Hays AP, Schon EA, DiMauro S (May 2002). "Cytochrome c oxidase deficiency due to a novel SCO2 mutation mimics Werdnig-Hoffmann disease". Archives of Neurology. 59 (5): 862–5. doi:10.1001/archneur.59.5.862. PMID 12020273.
  18. Tay SK, Shanske S, Kaplan P, DiMauro S (June 2004). "Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality". Archives of Neurology. 61 (6): 950–2. doi:10.1001/archneur.61.6.950. PMID 15210538.
  19. Joost K, Rodenburg R, Piirsoo A, van den Heuvel B, Zordania R, Ounap K (March 2010). "A novel mutation in the SCO2 gene in a neonate with early-onset cardioencephalomyopathy". Pediatric Neurology. 42 (3): 227–30. doi:10.1016/j.pediatrneurol.2009.10.004. PMID 20159436.
  20. 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 (January 2007). "IntAct--open source resource for molecular interaction data". Nucleic Acids Research. 35 (Database issue): D561–5. doi:10.1093/nar/gkl958. PMC 1751531. PMID 17145710.

Further reading
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