COX6A2
# COX6A2

Cytochrome c oxidase subunit VIa polypeptide 2 is a protein that in humans is encoded by the COX6A2 gene. Cytochrome c oxidase 6A2 is a subunit of the cytochrome c oxidase complex, also known as Complex IV, the last enzyme in the mitochondrial electron transport chain.

## Structure

The COX6A2 gene, located on the p arm of chromosome 16 in position 11.12, contains 3 exons and is 698 base pairs in length. The COX6A1 protein weighs 11 kDa and is composed of 97 amino acids. The protein is a subunit of Complex IV, a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. This nuclear gene encodes polypeptide 2 (heart/muscle isoform) of subunit VIa, and polypeptide 2 is present only in striated muscles. Polypeptide 1 (liver isoform) of subunit VIa is encoded by a different gene, COX6A1, and is found in all non-muscle tissues. These two polypeptides share 66% amino acid sequence identity.

## Function

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane to drive ATP synthesis via protonmotive force. The mitochondrially-encoded subunits perform the electron transfer of proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex.

Summary reaction:

    4 $Fe^{2+}-cytochrome$ c + 8 $H^+_{in}$ + $O_2$ → 4 $Fe^{3+}-cytochrome$ c + 2 $H_2O$ + 4 $H^+_{out}$

## Clinical significance

The Trans-activator of transcription protein (Tat) of human immunodeficiency virus (HIV) inhibits cytochrome c oxidase (COX) activity in permeabilized mitochondria isolated from both mouse and human liver, heart, and brain samples. Rapid loss of membrane potential $(ΔΨ_m)$ occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.

