SCO2

Last updated
SCO2
Available structures
PDB Ortholog search: PDBe RCSB
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
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 Mb Chr 15: 89.26 – 89.26 Mb
PubMed search [3] [4]
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. [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]

Contents

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]

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 mitochondria of eukaryotes.

<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 in humans is encoded by the MT-CO1 gene. In other eukaryotes, the gene is called COX1, CO1, or COI. Cytochrome c oxidase I is the main subunit of the cytochrome c oxidase complex. 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 subunit 2, also known as cytochrome c oxidase polypeptide II, is a protein that in humans 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">SCO1</span> Protein-coding gene in the species Homo sapiens

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. 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 deficiency.

<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">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">COX6A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 6A1, mitochondrial is a protein that in humans is encoded by the COX6A1 gene. Cytochrome c oxidase 6A1 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain. A mutation of the COX6A1 gene is associated with a recessive axonal or mixed form of Charcot-Marie-Tooth disease.

<span class="mw-page-title-main">COX7B</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 7B, mitochondrial (COX7B) is an enzyme that in humans is encoded by the COX7B gene. COX7B is a nuclear-encoded subunit of cytochrome c oxidase (COX). 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. Work with Oryzias latices has linked disruptions in COX7B with microphthalmia with linear skin lesions (MLS), microcephaly, and mitochondrial disease. Clinically, mutations in COX7B have been associated with linear skin defects with multiple congenital anomalies.

<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.

<span class="mw-page-title-main">COX8A</span> Protein-coding gene in the species Homo sapiens

Cytochrome c oxidase subunit 8A (COX8A) is a protein that in humans is encoded by the COX8A gene. Cytochrome c oxidase 8A is a subunit of the cytochrome c oxidase complex, also known as Complex IV. Mutations in the COX8A gene have been associated with complex IV deficiency with Leigh syndrome and epilepsy.

<span class="mw-page-title-main">Michaela Jaksch-Angerer</span>

Michaela Jaksch-Angerer is a German medical doctor, consultant in laboratory medicine, and Associate Professor for Clinical Chemistry. She has held the position of "Managing and Medical Director" since 2004 at the Freiburg Medical Laboratory Middle East LLC, Dubai, UAE, a member of Synlab since 2013. FML was founded in 2002 as a joint venture of the University of Freiburg Germany and the Al Abbas Group, Dubai, UAE.

<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.

Cytochrome c oxidase assembly factor 5 is a protein that in humans is encoded by the COA5 gene. This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency.

<span class="mw-page-title-main">COX14</span> Protein-coding gene in the species Homo sapiens

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.

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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000284194 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 5 "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. CC BY icon-80x15.png  This article incorporates [www.uniprot.org text]by UniProt available under the CC BY 4.0 license.
  12. 1 2 3 4 "SCO2 - Protein SCO2 homolog, mitochondrial precursor - Homo sapiens (Human) - SCO2 gene & protein". www.uniprot.org. Retrieved 2018-07-31. CC BY icon-80x15.png  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.

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