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SCO1

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SCO1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSCO1, SCOD1, SCO1 cytochrome c oxidase assembly protein, cytochrome c oxidase assembly protein, SCO cytochrome c oxidase assembly protein 1, synthesis of cytochrome C oxidase 1, MC4DN4
External IDsOMIM: 603644; MGI: 106362; HomoloGene: 3374; GeneCards: SCO1; OMA:SCO1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6341

52892

Ensembl

ENSG00000133028

ENSMUSG00000069844

UniProt

O75880

Q5SUC9

RefSeq (mRNA)

NM_004589

NM_001040026

RefSeq (protein)

NP_004580

NP_001035115

Location (UCSC)Chr 17: 10.67 – 10.7 MbChr 11: 66.94 – 66.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protein SCO1 homolog, mitochondrial, also known as SCO1, cytochrome c oxidase assembly protein, is a protein that in humans is encoded by the SCO1 gene.[5][6] SCO1 localizes predominantly to blood vessels, whereas SCO2 is barely detectable, as well as to tissues with high levels of oxidative phosphorylation. The expression of SCO2 is also much higher than that of SCO1 in muscle tissue, while SCO1 is expressed at higher levels in liver tissue than SCO2. Mutations in both SCO1 and SCO2 are associated with distinct clinical phenotypes as well as tissue-specific cytochrome c oxidase (complex IV) deficiency.[7][8][9]

Structure

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SCO1 is located on the p arm of chromosome 17 in position 13.1 and has 6 exons.[6] The SCO1 gene produces a 33.8 kDa protein composed of 301 amino acids.[10][11] 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.[8][9]

Function

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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.[6] It is predominantly expressed in muscle, heart, and brain tissues, which are also known for their high rates of oxidative phosphorylation.[5] 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-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 MT-CO2/COX2.[12][8][9][13]

Clinical relevance

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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.[13][14][8][9] 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.[14][15][16] 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.[13]

Interactions

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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, MT-CO2/COX2, COX18, and SCO2.[17][8][9][18]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000133028 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000069844 – 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. ^ a b Petruzzella V, Tiranti V, Fernandez P, Ianna P, Carrozzo R, Zeviani M (December 1998). "Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain". Genomics. 54 (3): 494–504. doi:10.1006/geno.1998.5580. PMID 9878253.
  6. ^ a b c "Entrez Gene: SCO1 SCO cytochrome oxidase deficient homolog 1 (yeast)".Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ Brosel S, Yang H, Tanji K, Bonilla E, Schon EA (November 2010). "Unexpected vascular enrichment of SCO1 over SCO2 in mammalian tissues: implications for human mitochondrial disease". The American Journal of Pathology. 177 (5): 2541–8. doi:10.2353/ajpath.2010.100229. PMC 2966810. PMID 20864674.
  8. ^ a b c d e "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  9. ^ a b c d e "SCO1 - Protein SCO1 homolog, mitochondrial precursor - Homo sapiens (Human) - SCO1 gene & protein". www.uniprot.org. Retrieved 2018-08-08. This article incorporates text available under the CC BY 4.0 license.
  10. ^ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-08-08.
  11. ^ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (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.
  12. ^ 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.
  13. ^ a b c 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.
  14. ^ a b Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rötig A (November 2000). "Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy". American Journal of Human Genetics. 67 (5): 1104–9. doi:10.1016/S0002-9297(07)62940-1. PMC 1288552. PMID 11013136.
  15. ^ Banci L, Bertini I, Ciofi-Baffoni S, Leontari I, Martinelli M, Palumaa P, Sillard R, Wang S (January 2007). "Human Sco1 functional studies and pathological implications of the P174L mutant". Proceedings of the National Academy of Sciences of the United States of America. 104 (1): 15–20. Bibcode:2007PNAS..104...15B. doi:10.1073/pnas.0606189103. PMC 1765425. PMID 17182746.
  16. ^ Leary SC, Antonicka H, Sasarman F, Weraarpachai W, Cobine PA, Pan M, Brown GK, Brown R, Majewski J, Ha KC, Rahman S, Shoubridge EA (October 2013). "Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic acidosis". Human Mutation. 34 (10): 1366–70. doi:10.1002/humu.22385. PMID 23878101. S2CID 43630957.
  17. ^ Lorenzi I, Oeljeklaus S, Aich A, Ronsör C, Callegari S, Dudek J, Warscheid B, Dennerlein S, Rehling P (February 2018). "The mitochondrial TMEM177 associates with COX20 during COX2 biogenesis". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1865 (2): 323–333. doi:10.1016/j.bbamcr.2017.11.010. PMC 5764226. PMID 29154948.
  18. ^ "127 binary interactions found for search term SCO1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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