COA6

COA6
Identifiers
AliasesCOA6, C1orf31, CEMCOX4, cytochrome c oxidase assembly factor 6
External IDsGeneCards: COA6
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q42.2Start234,373,456 bp[1]
End234,384,049 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

388753

n/a

Ensembl

ENSG00000168275

n/a

UniProt

Q5JTJ3

n/a

RefSeq (mRNA)

NM_001301733
NM_001012985
NM_001206641

n/a

RefSeq (protein)

NP_001013003
NP_001193570
NP_001288662

n/a

Location (UCSC)Chr 1: 234.37 – 234.38 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene.[3] 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.[4][5] The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family.[3][6] 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.[7] Mutations in this gene result in fatal infantile cardioencephalomyopathy.[6]

Structure

The COA6 gene is located on the q arm of chromosome 1 in position 42.2 and spans 10,612 base pairs.[3] The gene produces a 14.1 kDa protein composed of 125 amino acids.[8][9] The COA6 protein is found a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2.[4][5] This protein localizes to the intermembrane space, associating with the inner membrane and transmembrane proteins such as SCO2 and COX2.[7]

Function

The COA6 encodes a protein which is an assembly factor for Complex IV.[3] This protein is specifically required for COX2 biogenesis and stability; the absence of this protein will cause fast turnover of newly synthesized COX2. As a constituent of mitochondrial copper relay system, this protein possibly relays copper ions from SCO2 to COX2.[7]

Clinical Significance

Two mutations have been identified in this protein: W66R and W59C. The latter mutation results in the protein being mistargeted to the mitochondrial matrix, resulting in the loss of interaction with SCO2 and COX2.[4][5] Inheritance of this mutation is autosomal recessive and results in a phenotype of fatal infantile cardioencephalomyopathy due to Complex IV deficiency.[6] Symptoms include hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, and metabolic hypotonia.[4][5]

Interactions

This protein interacts transiently with the copper-containing catalytic domain of newly synthesized COX2 via its C-terminal tail exposed to the intermembrane space. It also interacts selectively with the copper metallochaperone SCO2 in a COX2-dependent manner and with COX20 in a COX2- and COX18-dependent manner.[7] Additionally, this protein interacts with COA1, SCO1, COX16, TTC19, DTX2, NADSYN1, GABARAP, AIFM1, COX4I1, CD81, COX14, SFXN1, and PLGRKT.[4][5][10]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000168275 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:".
  3. 1 2 3 4 "Entrez Gene: Cytochrome c oxidase assembly factor 6". Retrieved 2018-08-08.
  4. 1 2 3 4 5 "COA6 - Cytochrome c oxidase assembly factor 6 homolog - Homo sapiens (Human) - COA6 gene & protein". www.uniprot.org. Retrieved 2018-08-07.  This article incorporates text available under the CC BY 4.0 license.
  5. 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.
  6. 1 2 3 Online Mendelian Inheritance in Man (OMIM) 614772
  7. 1 2 3 4 Pacheu-Grau D, Bareth B, Dudek J, Juris L, Vögtle FN, Wissel M, et al. (June 2015). "Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies". Cell Metabolism. 21 (6): 823–33. doi:10.1016/j.cmet.2015.04.012. PMID 25959673.
  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. ↑ "COA6 - Cytochrome c oxidase assembly factor 6 homolog". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  10. ↑ IntAct. "COA6 interactions". www.ebi.ac.uk. Retrieved 2018-08-08.

Further reading

  • Hendrickson SL, Lautenberger JA, Chinn LW, Malasky M, Sezgin E, Kingsley LA, Goedert JJ, Kirk GD, Gomperts ED, Buchbinder SP, Troyer JL, O'Brien SJ (September 2010). "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLOS One. 5 (9): e12862. Bibcode:2010PLoSO...512862H. doi:10.1371/journal.pone.0012862. PMC 2943476. PMID 20877624.
  • Calvo SE, Compton AG, Hershman SG, Lim SC, Lieber DS, Tucker EJ, Laskowski A, Garone C, Liu S, Jaffe DB, Christodoulou J, Fletcher JM, Bruno DL, Goldblatt J, Dimauro S, Thorburn DR, Mootha VK (January 2012). "Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing". Science Translational Medicine. 4 (118): 118ra10. doi:10.1126/scitranslmed.3003310. PMC 3523805. PMID 22277967.
  • Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA, Gloerich J, Lasonder E, van den Heuvel LP, Nijtmans LG, Huynen MA (February 2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase". Genome Biology. 13 (2): R12. doi:10.1186/gb-2012-13-2-r12. PMC 3334569. PMID 22356826.
  • Szklarczyk R, Wanschers BF, Cuypers TD, Esseling JJ, Riemersma M, van den Brand MA, Gloerich J, Lasonder E, van den Heuvel LP, Nijtmans LG, Huynen MA (February 2012). "Iterative orthology prediction uncovers new mitochondrial proteins and identifies C12orf62 as the human ortholog of COX14, a protein involved in the assembly of cytochrome c oxidase". Genome Biology. 13 (2): R12. doi:10.1186/gb-2012-13-2-r12. PMC 3334569. PMID 22356826.
  • Pacheu-Grau D, Bareth B, Dudek J, Juris L, Vögtle FN, Wissel M, Leary SC, Dennerlein S, Rehling P, Deckers M (June 2015). "Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies". Cell Metabolism. 21 (6): 823–33. doi:10.1016/j.cmet.2015.04.012. PMID 25959673.

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.