// Workers AI · dad joke modeWhat did SCO2 say to its friend? "Let's bond.

For sCO₂, the phase of carbon dioxide, see supercritical carbon dioxide.

SCO2
Identifiers
Aliases	SCO2, 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 IDs	OMIM: 604272; MGI: 3818630; HomoloGene: 68444; GeneCards: SCO2; OMA:SCO2 - orthologs
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RLI
Gene location (Human) Chr. Chromosome 22 (human) Band 22q13.33 Start 50,523,568 bp End 50,526,461 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15|15 E3 Start 89,255,840 bp End 89,258,049 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube granulocyte mucosa of transverse colon monocyte gingival epithelium gonad palpebral conjunctiva periodontal fiber right lobe of liver epithelium of bronchus Top expressed in yolk sac blastocyst embryo duodenum colon proximal tubule right kidney muscle of thigh jejunum morula More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding copper ion binding metal ion binding protein-disulfide reductase activity Cellular component myofibril mitochondrial matrix mitochondrial inner membrane mitochondrion integral component of mitochondrial inner membrane membrane integral component of membrane Biological process cellular copper ion homeostasis copper ion transport eye development respiratory chain complex IV assembly cell redox homeostasis mitochondrial cytochrome c oxidase assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 15: 89.26 – 89.26 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. 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. 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.

Structure

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

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. 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 COX. 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.

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). 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. 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. A mutation of 1602T>G has been found to result in rapidly progressive disease phenotypes. 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.

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.

Further reading

• Jaksch M, Ogilvie I, Yao J, Kortenhaus G, Bresser HG, Gerbitz KD, Shoubridge EA (March 2000). "Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency". Human Molecular Genetics. 9 (5): 795–801. doi:10.1093/hmg/9.5.795. PMID 10749987.
• 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 (October 2001). "Homozygosity (E140K) in SCO2 causes delayed infantile onset of cardiomyopathy and neuropathy". Neurology. 57 (8): 1440–6. doi:10.1212/wnl.57.8.1440. PMID 11673586. S2CID 24920023.
• 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.
• Salviati L, Hernandez-Rosa E, Walker WF, Sacconi S, DiMauro S, Schon EA, Davidson MM (April 2002). "Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations". The Biochemical Journal. 363 (Pt 2): 321–7. doi:10.1042/0264-6021:3630321. PMC 1222481. PMID 11931660.
• Collins JE, Goward ME, Cole CG, Smink LJ, Huckle EJ, Knowles S, Bye JM, Beare DM, Dunham I (January 2003). "Reevaluating human gene annotation: a second-generation analysis of chromosome 22". Genome Research. 13 (1): 27–36. doi:10.1101/gr.695703. PMC 430954. PMID 12529303.
• Sacconi S, Salviati L, Sue CM, Shanske S, Davidson MM, Bonilla E, Naini AB, De Vivo DC, DiMauro S (February 2003). "Mutation screening in patients with isolated cytochrome c oxidase deficiency". Pediatric Research. 53 (2): 224–30. doi:10.1203/01.PDR.0000048100.91730.6A. hdl:11577/1368344. PMID 12538779. S2CID 12496207.
• 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 (June 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
• Leary SC, Kaufman BA, Pellecchia G, Guercin GH, Mattman A, Jaksch M, Shoubridge EA (September 2004). "Human SCO1 and SCO2 have independent, cooperative functions in copper delivery to cytochrome c oxidase". Human Molecular Genetics. 13 (17): 1839–48. doi:10.1093/hmg/ddh197. PMID 15229189.
• 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 (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
• Stiburek L, Vesela K, Hansikova H, Pecina P, Tesarova M, Cerna L, Houstek J, Zeman J (December 2005). "Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1". The Biochemical Journal. 392 (Pt 3): 625–32. doi:10.1042/BJ20050807. PMC 1316303. PMID 16083427.
• Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM (June 2006). "p53 regulates mitochondrial respiration". Science. 312 (5780): 1650–3. Bibcode:2006Sci...312.1650M. doi:10.1126/science.1126863. PMID 16728594. S2CID 36668814.
• Leary SC, Cobine PA, Kaufman BA, Guercin GH, Mattman A, Palaty J, Lockitch G, Winge DR, Rustin P, Horvath R, Shoubridge EA (January 2007). "The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory roles in the maintenance of cellular copper homeostasis". Cell Metabolism. 5 (1): 9–20. doi:10.1016/j.cmet.2006.12.001. PMID 17189203.
• Banci L, Bertini I, Ciofi-Baffoni S, Gerothanassis IP, Leontari I, Martinelli M, Wang S (September 2007). "A structural characterization of human SCO2". Structure. 15 (9): 1132–40. doi:10.1016/j.str.2007.07.011. PMID 17850752.

External links

• SCO2 human gene location in the UCSC Genome Browser.
• SCO2 human gene details in the UCSC Genome Browser.