COX6A2

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

Structure
The COX6A2 gene, located on the p arm of is_associated_with::chromosome 16 in position 11.12, contains 3 is_associated_with::exons and is 698 is_associated_with::base pairs in length. The COX6A1 protein weighs 11 kDa and is composed of 97 is_associated_with::amino acids. The protein is a subunit of is_associated_with::Complex IV, a is_associated_with::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, is_associated_with::COX6A1, and is found in all non-muscle tissues. These two is_associated_with::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 Fe2+-cytochrome c + 8 H+in + O2 → 4 Fe3+-cytochrome c + 2 H2O + 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 is_associated_with::membrane potential (ΔΨm) occurs with submicromolar doses of Tat, and cytochrome c is released from the mitochondria.