COA6
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6 gene.[5] 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.[6][7] The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family.[5][8] 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.[9] Mutations in this gene result in fatal infantile cardioencephalomyopathy.[8]
| COA6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | COA6, C1orf31, CEMCOX4, cytochrome c oxidase assembly factor 6, MC4DN13 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 614772; MGI: 1915142; GeneCards: COA6; OMA:COA6 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
The COA6 gene is located on the q arm of chromosome 1 in position 42.2 and spans 10,612 base pairs.[5] The gene produces a 14.1 kDa protein composed of 125 amino acids.[10][11] The COA6 protein is found a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2.[6][7] The protein has a CX9CXnCX10C motif and a CHCH domain, which hints that the protein is most likely a redox protein rather than a copper metallochaperone.[12][13]
Function
The COA6 encodes a protein which is an assembly factor for Complex IV.[5] This protein is specifically required for COX2 biogenesis and stability; the absence of this protein will cause fast turnover of newly synthesized COX2.The presence of a CHCH domain facilitates its function as a thiol-disulfide reductant as it facilitates the transfer of copper from SCO1 to COX2.[12]
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.[6][7] Inheritance of this mutation is autosomal recessive and results in a phenotype of fatal infantile cardioencephalomyopathy due to Complex IV deficiency.[8] Symptoms include hypertrophic cardiomyopathy, left ventricular non-compaction, lactic acidosis, and metabolic hypotonia.[6][7]
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.[9] Additionally, this protein interacts with COA1, SCO1, COX16, TTC19, DTX2, NADSYN1, GABARAP, AIFM1, COX4I1, CD81, COX14, SFXN1, and PLGRKT.[6][7][14]
