SCO1

SCO1 is located on the p arm of chromosome 17 in position 13.1 and has 6 exons. The SCO1 gene produces a 33.8 kDa protein composed of 301 amino acids.{{Cite web|url=https://amino.heartproteome.org/web/protein/O75880|title=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information|last=Yao|first=Daniel|website=amino.heartproteome.org|access-date=2018-08-08}}{{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 | display-authors = 6 | 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 }} The protein is a member of the SCO1/2 family. It contains 3 copper metal binding sites at positions 169, 173, and 260, a transit peptide, a 25 amino acid topological domain from positions 68–92, a 19 amino acid helical transmembrane domain from positions 93–111, and a 190 amino acid topological domain from positions 112–301 in the mitochondrial intermembrane. Additionally, SCO1 has been predicted to contain 10 beta-strands, 7 helixes, and 2 turns and is a single-pass membrane protein.

Mammalian cytochrome c oxidase (COX) catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. In yeast, 2 related COX assembly genes, SCO1 and SCO2 (synthesis of cytochrome c oxidase), enable subunits 1 and 2 to be incorporated into the holoprotein. This gene is the human homolog to the yeast SCO1 gene. It is predominantly expressed in muscle, heart, and brain tissues, which are also known for their high rates of oxidative phosphorylation. SCO1 is a copper metallochaperone that is located in the inner mitochondrial membrane and is important for the maturation and stabilization of cytochrome c oxidase subunit II (MT-{{not a typo|CO2}}/COX2). It plays a role in the regulation of copper homeostasis by controlling the localization and abundance of CTR1 and is responsible for the transportation of copper to the Cu(A) site on {{not a typo|MT-CO2/COX2}}.{{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 = }}

Mutations in the SCO1 gene are associated with hepatic failure and encephalopathy resulting from mitochondrial complex IV deficiency also known as cytochrome c oxidase deficiency. This is a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly, and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development, mental retardation, and lactic acidosis. Some affected individuals manifest fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients also suffers from Leigh syndrome.{{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 = Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rötig A | title = Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy | journal = American Journal of Human Genetics | volume = 67 | issue = 5 | pages = 1104–9 | date = November 2000 | pmid = 11013136 | pmc = 1288552 | doi = 10.1016/S0002-9297(07)62940-1 }} Specifically, cases of pathogenic SCO1 mutations have resulted in fatal infantile encephalopathy, neonatal-onset hepatic failure, and severe hepatopathy. The P174L and M294V mutations have been identified and implicated in these diseases and phenotypes.{{cite journal | vauthors = Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S | title = Human Sco1 functional studies and pathological implications of the P174L mutant | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 1 | pages = 15–20 | date = January 2007 | pmid = 17182746 | pmc = 1765425 | doi = 10.1073/pnas.0606189103 | bibcode = 2007PNAS..104...15B | doi-access = free }}{{cite journal | vauthors = Leary SC, Antonicka H, Sasarman F, Weraarpachai W, Cobine PA, Pan M, Brown GK, Brown R, Majewski J, Ha KC, Rahman S, Shoubridge EA | title = Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic acidosis | journal = Human Mutation | volume = 34 | issue = 10 | pages = 1366–70 | date = October 2013 | pmid = 23878101 | doi = 10.1002/humu.22385 | s2cid = 43630957 }} It has also been suggested that mutations in SCO1, as well as SCO2, can result in a cellular copper deficiency, which can occur separately from cytochrome c oxidase assembly defects.

SCO1 has been shown to have 127 binary protein-protein interactions including 120 co-complex interactions. SCO1 interacts with COA6, TMEM177, COX20, COX16, COX17, WDR19, CIDEB, and UBC7. It is also found in a complex with TMEM177, COX20, COA6, Cytochrome c oxidase subunit II, COX18, and SCO2.{{cite journal | vauthors = Lorenzi I, Oeljeklaus S, Aich A, Ronsör C, Callegari S, Dudek J, Warscheid B, Dennerlein S, Rehling P | title = The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1865 | issue = 2 | pages = 323–333 | date = February 2018 | pmid = 29154948 | pmc = 5764226 | doi = 10.1016/j.bbamcr.2017.11.010 }}{{cite web | url = https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=SCO1 | title = 127 binary interactions found for search term SCO1 | work = IntAct Molecular Interaction Database | publisher = EMBL-EBI | access-date = 2018-08-25 }}

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• {{cite journal | vauthors = Shoubridge EA | title = Cytochrome c oxidase deficiency | journal = American Journal of Medical Genetics | volume = 106 | issue = 1 | pages = 46–52 | year = 2001 | pmid = 11579424 | doi = 10.1002/ajmg.1378 }}
• {{cite journal | vauthors = Schulze M, Rödel G | title = Accumulation of the cytochrome c oxidase subunits I and II in yeast requires a mitochondrial membrane-associated protein, encoded by the nuclear SCO1 gene | journal = Molecular & General Genetics | volume = 216 | issue = 1 | pages = 37–43 | date = March 1989 | pmid = 2543907 | doi = 10.1007/BF00332228 | s2cid = 13029649 }}
• {{cite journal | vauthors = Schulze M, Rödel G | title = SCO1, a yeast nuclear gene essential for accumulation of mitochondrial cytochrome c oxidase subunit II | journal = Molecular & General Genetics | volume = 211 | issue = 3 | pages = 492–8 | date = March 1988 | pmid = 2835635 | doi = 10.1007/BF00425706 | s2cid = 25345429 }}
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• {{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 | s2cid = 7599827 | doi-access = | bibcode = 1999FEBSL.447...65P }}
• {{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 }}
• {{cite journal | vauthors = Horvath R, Lochmüller H, Stucka R, Yao J, Shoubridge EA, Kim SH, Gerbitz KD, Jaksch M | title = Characterization of human SCO1 and COX17 genes in mitochondrial cytochrome-c-oxidase deficiency | journal = Biochemical and Biophysical Research Communications | volume = 276 | issue = 2 | pages = 530–3 | date = September 2000 | pmid = 11027508 | doi = 10.1006/bbrc.2000.3495 }}
• {{cite journal | vauthors = Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA | title = Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein | journal = The Journal of Biological Chemistry | volume = 280 | issue = 15 | pages = 15202–11 | date = April 2005 | pmid = 15659396 | doi = 10.1074/jbc.M410705200 | doi-access = free }}
• {{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 }}
• {{cite journal | vauthors = Cobine PA, Pierrel F, Leary SC, Sasarman F, Horng YC, Shoubridge EA, Winge DR | title = The P174L mutation in human Sco1 severely compromises Cox17-dependent metallation but does not impair copper binding | journal = The Journal of Biological Chemistry | volume = 281 | issue = 18 | pages = 12270–6 | date = May 2006 | pmid = 16520371 | doi = 10.1074/jbc.M600496200 | doi-access = free }}
• {{cite journal | vauthors = Banci L, Bertini I, Calderone V, Ciofi-Baffoni S, Mangani S, Martinelli M, Palumaa P, Wang S | title = A hint for the function of human Sco1 from different structures | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 23 | pages = 8595–600 | date = June 2006 | pmid = 16735468 | pmc = 1482625 | doi = 10.1073/pnas.0601375103 | bibcode = 2006PNAS..103.8595B | doi-access = free }}
• {{cite journal | vauthors = Leary SC, Sasarman F, Nishimura T, Shoubridge EA | title = Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1 | journal = Human Molecular Genetics | volume = 18 | issue = 12 | pages = 2230–40 | date = June 2009 | pmid = 19336478 | doi = 10.1093/hmg/ddp158 | doi-access = free }}
• {{cite journal | vauthors = Stiburek L, Vesela K, Hansikova H, Hulkova H, Zeman J | title = Loss of function of Sco1 and its interaction with cytochrome c oxidase | journal = American Journal of Physiology. Cell Physiology | volume = 296 | issue = 5 | pages = C1218–26 | date = May 2009 | pmid = 19295170 | doi = 10.1152/ajpcell.00564.2008 | s2cid = 22826017 }}

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Category:Genes mutated in mice