SCO1

Last updated
SCO1
Protein SCO1 PDB 1wp0.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SCO1 , 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 IDs OMIM: 603644 MGI: 106362 HomoloGene: 3374 GeneCards: SCO1
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 Mb Chr 11: 66.94 – 66.96 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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

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

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

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]

Model organisms

Model organisms have been used in the study of SCO1 function. A conditional knockout mouse line, called Sco1tm1a(KOMP)Wtsi [20] [21] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease. [22] [23] [24]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. [18] [25] Twenty-two tests were carried out on mutant mice and two significant abnormalities were observed. [18] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals. [18]

Interactions

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. [26] [8] [9] [27]

Related Research Articles

<span class="mw-page-title-main">Cytochrome c oxidase</span> Complex enzyme found in bacteria, archaea, and mitochondria of eukaryotes

The enzyme cytochrome c oxidase or Complex IV, is a large transmembrane protein complex found in bacteria, archaea, and the mitochondria of eukaryotes.

<span class="mw-page-title-main">MT-RNR1</span> SSU rRNA of the mitochondrial ribosome

Mitochondrially encoded 12S ribosomal RNA is the SSU rRNA of the mitochondrial ribosome. In humans, 12S is encoded by the MT-RNR1 gene and is 959 nucleotides long. MT-RNR1 is one of the 37 genes contained in animal mitochondria genomes. Their 2 rRNA, 22 tRNA and 13 mRNA genes are very useful in phylogenetic studies, in particular the 12S and 16S rRNAs. The 12S rRNA is the mitochondrial homologue of the prokaryotic 16S and eukaryotic nuclear 18S ribosomal RNAs. Mutations in the MT-RNR1 gene may be associated with hearing loss. The rRNA gene also encodes a peptide MOTS-c, also known as Mitochondrial-derived peptide MOTS-c or Mitochondrial open reading frame of the 12S rRNA-c.

<span class="mw-page-title-main">Cytochrome c oxidase subunit I</span> Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase I (COX1) also known as mitochondrially encoded cytochrome c oxidase I (MT-CO1) is a protein that is encoded by the MT-CO1 gene in eukaryotes. The gene is also called COX1, CO1, or COI. Cytochrome c oxidase I is the main subunit of the cytochrome c oxidase complex. In humans, mutations in MT-CO1 have been associated with Leber's hereditary optic neuropathy (LHON), acquired idiopathic sideroblastic anemia, Complex IV deficiency, colorectal cancer, sensorineural deafness, and recurrent myoglobinuria.

<span class="mw-page-title-main">Cytochrome c oxidase subunit 2</span> Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase II is a protein in eukaryotes that is encoded by the MT-CO2 gene. Cytochrome c oxidase subunit II, abbreviated COXII, COX2, COII, or MT-CO2, is the second subunit of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV.

<span class="mw-page-title-main">Cytochrome c oxidase subunit III</span> Enzyme of the respiratory chain encoded by the mitochondrial genome

Cytochrome c oxidase subunit III (COX3) is an enzyme that in humans is encoded by the MT-CO3 gene. It is one of main transmembrane subunits of cytochrome c oxidase. It is also one of the three mitochondrial DNA (mtDNA) encoded subunits of respiratory complex IV. Variants of it have been associated with isolated myopathy, severe encephalomyopathy, Leber hereditary optic neuropathy, mitochondrial complex IV deficiency, and recurrent myoglobinuria.

<span class="mw-page-title-main">SURF1</span> Protein-coding gene in the species Homo sapiens

Surfeit locus protein 1 (SURF1) is a protein that in humans is encoded by the SURF1 gene. The protein encoded by SURF1 is a component of the mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex, which is involved in the regulation of cytochrome c oxidase assembly. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency, and Charcot-Marie-Tooth disease 4K (CMT4K).

<span class="mw-page-title-main">SCO2</span> Protein-coding gene in the species Homo sapiens

SCO2 cytochrome c oxidase assembly 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. 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.

<span class="mw-page-title-main">COX17</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase copper chaperone is a protein that in humans is encoded by the COX17 gene.

<span class="mw-page-title-main">COX4I1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1) is an enzyme that in humans is encoded by the COX4I1 gene. COX4I1 is a nuclear-encoded isoform of cytochrome c oxidase (COX) subunit 4. Cytochrome c oxidase is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane, acting as the terminal enzyme of the mitochondrial respiratory chain. Antibodies against COX4 can be used to identify the inner membrane of mitochondria in immunofluorescence studies. Mutations in COX4I1 have been associated with COX deficiency and Fanconi anemia.

<span class="mw-page-title-main">TUFM</span> Mitochondrial protein and coding gene in humans

Elongation factor Tu, mitochondrial is a protein that in humans is encoded by the TUFM gene. It is an EF-Tu homolog.

<span class="mw-page-title-main">COX6B1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6B1 is an enzyme that in humans is encoded by the COX6B1 gene. Cytochrome c oxidase 6B1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. Mutations of the COX6B1 gene are associated with severe infantile encephalomyopathy and mitochondrial complex IV deficiency (MT-C4D).

<span class="mw-page-title-main">COX10</span> Mammalian protein found in Homo sapiens

Protoheme IX farnesyltransferase, mitochondrial is an enzyme that in humans is encoded by the COX10 gene. Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene, COX10, encodes heme A: farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A duplication and with HNPP deletion.

<span class="mw-page-title-main">COX15</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase assembly protein COX15 homolog (COX15), also known as heme A synthase, is a protein that in humans is encoded by the COX15 gene. This protein localizes to the inner mitochondrial membrane and involved in heme A biosynthesis. COX15 is also part of a three-component mono-oxygenase that catalyses the hydroxylation of the methyl group at position eight of the protoheme molecule. Mutations in this gene has been reported in patients with hypertrophic cardiomyopathy as well as Leigh syndrome, and characterized by delayed onset of symptoms, hypotonia, feeding difficulties, failure to thrive, motor regression, and brain stem signs.

Mitochondrially encoded tRNA leucine 2 (CUN) also known as MT-TL2 is a transfer RNA which in humans is encoded by the mitochondrial MT-TL2 gene.

<span class="mw-page-title-main">COA3</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase assembly factor 3, also known as Coiled-coil domain-containing protein 56, or Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 12 kDa is a protein that in humans is encoded by the COA3 gene. This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function.

<span class="mw-page-title-main">COX14</span> Protein-coding gene in humans

Cytochrome c oxidase assembly factor COX14 is a protein that in humans is encoded by the COX14 gene. This gene encodes a small single-pass transmembrane protein that localizes to mitochondria. This protein may play a role in coordinating the early steps of cytochrome c oxidase subunit assembly and, in particular, the synthesis and assembly of the COX I subunit of the holoenzyme. Mutations in this gene have been associated with mitochondrial complex IV deficiency. Alternative splicing results in multiple transcript variants.

<span class="mw-page-title-main">COA7</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase assembly factor 7 (putative) (COA7), also known as Beta-lactamase hap-like protein, Respiratory chain assembly factor 1 (RESA1), Sel1 repeat-containing protein 1 (SELRC1), or C1orf163 is a protein that in humans is encoded by the COA7 gene. The protein encoded by COA7 is an assembly factor important for the mitochondrial respiratory chain. Mutations in COA7 have been associated with cytochrome c oxidase deficiency resulting in spinocerebellar ataxia with axonal neuropathy type 3 and mitochondrial myopathy.

Cytochrome c oxidase assembly factor COX20 is a protein that in humans is encoded by the COX20 gene. This gene encodes a protein that plays a role in the assembly of cytochrome c oxidase, an important component of the respiratory pathway. Mutations in this gene can cause mitochondrial complex IV deficiency. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants.

<span class="mw-page-title-main">COA6</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene. Mitochondrial respiratory chain Complex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane space cytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis. The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family. This protein is located in the intermembrane space, associating with SCO2 and COX2. It stabilizes newly formed COX2 and is part of the mitochondrial copper relay system. Mutations in this gene result in fatal infantile cardioencephalomyopathy.

<span class="mw-page-title-main">CEP89</span> Protein-coding gene in the species Homo sapiens

Centrosomal protein 89, also known as Centrosomal protein of 89 kDa (CEP89), Centrosomal protein 123 (CEP123), or Coiled-coil domain-containing protein 123 is a protein that in humans is encoded by the CEP89 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000133028 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 3 "Entrez Gene: SCO1 SCO cytochrome oxidase deficient homolog 1 (yeast)".PD-icon.svg 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. 1 2 3 4 5 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC   5210571 . PMID   27899622.
  9. 1 2 3 4 5 "SCO1 - Protein SCO1 homolog, mitochondrial precursor - Homo sapiens (Human) - SCO1 gene & protein". www.uniprot.org. Retrieved 2018-08-08. Creative Commons by small.svg  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. 1 2 3 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. 1 2 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. ↑ "Salmonella infection data for Sco1". Wellcome Trust Sanger Institute.
  18. 1 2 3 4 Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
  19. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  20. ↑ "International Knockout Mouse Consortium".
  21. ↑ "Mouse Genome Informatics".
  22. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
  23. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID   21677718.
  24. ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
  25. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi: 10.1186/gb-2011-12-6-224 . PMC   3218837 . PMID   21722353.
  26. ↑ 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.
  27. ↑ "127 binary interactions found for search term SCO1". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.

Further reading

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