COA3

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.[4][5][6]

COA3
Identifiers
Aliases	COA3, CCDC56, MITRAC12, HSPC009, cytochrome c oxidase assembly factor 3, COX25
External IDs	OMIM: 614775 MGI: 1098757 HomoloGene: 69156 GeneCards: COA3
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.2 Start 42,795,147 bp[1] End 42,798,704 bp[1]
Gene ontology Molecular function • GO:0001948 protein binding Cellular component • integral component of membrane • mitochondrial inner membrane • membrane • mitochondrion • integral component of mitochondrial inner membrane • mitochondrial respiratory chain complex IV Biological process • mitochondrial respiratory chain complex IV assembly • positive regulation of mitochondrial translation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	28958	52469
Ensembl	ENSG00000183978	n/a
UniProt	Q9Y2R0	Q9D2R6
RefSeq (mRNA)	NM_001040431	NM_026618
RefSeq (protein)	NP_001035521	NP_080894
Location (UCSC)	Chr 17: 42.8 – 42.8 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Structure

The COA3 gene is located on the q arm of chromosome 17 at position 21.2 and it spans 1,107 base pairs.[6] The COA3 gene produces a 7.8 kDa protein composed of 71 amino acids.[7][8] COA3 is a component of the enzyme MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, and the structure contains a C-terminal coiled-coil domain as well as a central single pass transmembrane domain.[9]

Function

The COA3 gene encodes for a Core protein of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex. The MITRAC complex is essential in the assembly of cytochrome c oxidase (complex IV) of the mitochondrial respiratory chain, which is responsible for the catalysis of oxidation of cytochrome c by molecular oxygen.[10] The MITRAC complex regulates both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. In addition, COA3 is required for efficient translation of MT-CO1 and assembly of the mitochondrial respiratory chain complex IV.[4][5]

Clinical significance

Variants of COA3 have been associated with the mitochonrdial Complex IV deficiency, a deficiency in an enzyme complex of the mitochondrial respiratory chain which catalyzes the oxidation of cytochrome c utilizing molecular oxygen.[10] The deficiency is characterized by heterogeneous phenotypes ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Other Clinical Manifestations include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation.[11] A missense mutation of c.215A>G in the COA3 gene has been found to result in a severe decrease in protein levels with symptoms of exercise intolerance and peripheral neuropathy.[10]

Interactions

Like COX14, COA3 is a key component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex.[12] In addition, it has interactions with proteins such as MT-CO1, COX1, SMIM20, SURF1, TIMM21, and others.[13][4]

References

1. GRCh38: Ensembl release 89: ENSG00000183978 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "COA3 - Cytochrome c oxidase assembly factor 3 homolog, mitochondrial - Homo sapiens (Human) - COA3 gene & protein". Retrieved 2018-08-07. This article incorporates text available under the CC BY 4.0 license.
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. "Entrez Gene: Cytochrome c oxidase assembly factor 3". Retrieved 2018-08-07.
7. 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.
8. "Cytochrome c oxidase assembly factor 3 homolog, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-08. Retrieved 2018-08-07.
9. Peralta S, Clemente P, Sánchez-Martínez A, Calleja M, Hernández-Sierra R, Matsushima Y, Adán C, Ugalde C, Fernández-Moreno MÁ, Kaguni LS, Garesse R (July 2012). "Coiled coil domain-containing protein 56 (CCDC56) is a novel mitochondrial protein essential for cytochrome c oxidase function". The Journal of Biological Chemistry. 287 (29): 24174–85. doi:10.1074/jbc.M112.343764. PMC 3397844. PMID 22610097.
10. Ostergaard E, Weraarpachai W, Ravn K, Born AP, Jønson L, Duno M, Wibrand F, Shoubridge EA, Vissing J (March 2015). "Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature". Journal of Medical Genetics. 52 (3): 203–7. doi:10.1136/jmedgenet-2014-102914. PMID 25604084.
11. "Mitochondrial complex IV deficiency". www.uniprot.org.
12. Mick DU, Dennerlein S, Wiese H, Reinhold R, Pacheu-Grau D, Lorenzi I, Sasarman F, Weraarpachai W, Shoubridge EA, Warscheid B, Rehling P (December 2012). "MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation". Cell. 151 (7): 1528–41. doi:10.1016/j.cell.2012.11.053. PMID 23260140.
13. Dennerlein S, Oeljeklaus S, Jans D, Hellwig C, Bareth B, Jakobs S, Deckers M, Warscheid B, Rehling P (September 2015). "MITRAC7 Acts as a COX1-Specific Chaperone and Reveals a Checkpoint during Cytochrome c Oxidase Assembly". Cell Reports. 12 (10): 1644–55. doi:10.1016/j.celrep.2015.08.009. PMID 26321642.

Further reading

• 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.
• Clemente P, Peralta S, Cruz-Bermudez A, Echevarría L, Fontanesi F, Barrientos A, Fernandez-Moreno MA, Garesse R (March 2013). "hCOA3 stabilizes cytochrome c oxidase 1 (COX1) and promotes cytochrome c oxidase assembly in human mitochondria". The Journal of Biological Chemistry. 288 (12): 8321–31. doi:10.1074/jbc.M112.422220. PMC 3605650. PMID 23362268.
• Ban-Ishihara R, Tomohiro-Takamiya S, Tani M, Baudier J, Ishihara N, Kuge O (October 2015). "COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1". FEBS Letters. 589 (20 Pt B): 3126–32. doi:10.1016/j.febslet.2015.08.039. PMID 26358295.

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