Cytochrome c oxidase assembly factor 6 is a protein that in humans is encoded by the COA6gene.[1]Mitochondrial respiratory chainComplex IV, or cytochrome c oxidase, is the component of the respiratory chain that catalyzes the transfer of electrons from intermembrane spacecytochrome c to molecular oxygen in the matrix and as a consequence contributes to the proton gradient involved in mitochondrial ATP synthesis.[2][3] The COA6 gene encodes an assembly factor for mitochondrial complex IV and is a member of the cytochrome c oxidase subunit 6B family.[1][4] 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.[5]Mutations in this gene result in fatal infantile cardioencephalomyopathy.[4]
The COA6 gene is located on the q arm of chromosome 1 in position 42.2 and spans 10,612 base pairs.[1] The gene produces a 14.1 kDa protein composed of 125 amino acids.[6][7] The COA6 protein is found a complex with TMEM177, COX20, MT-CO2/COX2, COX18, SCO1 and SCO2.[2][3] This protein localizes to the intermembrane space, associating with the inner membrane and transmembrane proteins such as SCO2 and COX2.[5]
Function
The COA6 encodes a protein which is an assembly factor for Complex IV.[1] 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.[5]
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.[5] Additionally, this protein interacts with COA1, SCO1, COX16, TTC19, DTX2, NADSYN1, GABARAP, AIFM1, COX4I1, CD81, COX14, SFXN1, and PLGRKT.[2][3][8]
↑ 5.05.15.25.3Pacheu-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. PMID25959673.
