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.[1]

Structure

The COA5 gene is located on the q arm of chromosome 2 at position 11.2 and it spans 9,195 base pairs.[1] The COA5 gene produces an 8 kDa protein composed of 73 amino acids.[2][3] The structure of the protein contains the twin CX9C motif of yeast Pet191, which is conserved in the 74-amino acid deduced human protein. An example of the twin CX9C would be a repeated motif of 2 cysteines.[4]

Function

The COA3 gene encodes for a protein involved in an early step of the complex IV assembly process.[5][6] The conserved cysteines in the twin CX9C motif, which is a part of the COA3 protein, has been shown to be essential in cell viability as well as the proper function and assembly of the cytochrome c oxidase complex.[4]

Clinical significance

Variants of COA5 have been mainly associated with a mitochondrial complex IV deficiency, a deficiency of the enzyme complex Complex IV, which is responsible for the catalysis of oxidation of cytochrome c using molecular oxygen. The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other phenotypes include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation.[7][1] Mutations in COA5 has also known to be associated with Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 (CEMCOX3). CEMCOX3 is an infantile disorder associated with a severely fatal course during the first weeks of life. It is characterized by hypertrophic cardiomyopathy and is caused by mitochondrial complex IV deficiency. Postmortem microscopic investigations have shown accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation.[5][6] A homozygous mutation of 157G>C has resulted in decreased complex IV in fibroblasts and heart muscle.[8]

Interactions

COA5 has been known to have unique protein–protein interactions with APP, KRT31, and CHCHD4.[9]

References

  1. 1 2 3 "Entrez Gene: Cytochrome c oxidase assembly factor 5". Retrieved 2018-08-07.
  2. ↑ 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 (Oct 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.
  3. ↑ "Cytochrome c oxidase assembly factor 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-08. Retrieved 2018-08-07.
  4. 1 2 Khalimonchuk, O; Rigby, K; Bestwick, M; Pierrel, F; Cobine, PA; Winge, DR (August 2008). "Pet191 is a cytochrome c oxidase assembly factor in Saccharomyces cerevisiae". Eukaryotic Cell. 7 (8): 1427–31. doi:10.1128/EC.00132-08. PMC 2519776. PMID 18503002.
  5. 1 2 "COA5 - Cytochrome c oxidase assembly factor 5 - Homo sapiens (Human) - COA5 gene & protein". www.uniprot.org. Retrieved 2018-08-07. This article incorporates [www.uniprot.org text] by UniProt available under the CC BY 4.0 license.
  6. 1 2 "UniProt: the universal protein knowledgebase". Nucleic Acids Research. 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMC 5210571. PMID 27899622.
  7. ↑ "Mitochondrial complex IV deficiency". www.uniprot.org.
  8. ↑ Huigsloot M, Nijtmans LG, Szklarczyk R, Baars MJ, van den Brand MA, Hendriksfranssen MG, van den Heuvel LP, Smeitink JA, Huynen MA, Rodenburg RJ (April 2011). "A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy". Am. J. Hum. Genet. 88 (4): 488–93. doi:10.1016/j.ajhg.2011.03.002. PMC 3071910. PMID 21457908.
  9. ↑ 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. CiteSeerX 10.1.1.279.8196. doi:10.1093/nar/gkl958. PMC 1751531. PMID 17145710.

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