COX6A2
Function
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix. Plays a role in the assembly and stabilization of complex IV (PubMed:31155743).
Involvement in disease
Mitochondrial complex IV deficiency, nuclear type 18
MC4DN18
An autosomal recessive, muscle-specific, mitochondrial disorder with onset in infancy. MC4DN18 is characterized by hypotonia, limb and facial muscle weakness, and high arched palate. Some patients have respiratory insufficiency at birth and cardiomyopathy. Patient skeletal muscle shows decreased levels and activity of mitochondrial respiratory complex IV.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Energy metabolism; oxidative phosphorylation.
Sequence Similarities
Belongs to the cytochrome c oxidase subunit 6A family.
Tissue Specificity
Expressed specifically in heart and muscle (PubMed:31155743). Not detected in brain, colon, spleen, kidney, liver, lung and pancreas (PubMed:31155743).
Cellular localization
- Mitochondrion inner membrane
- Single-pass membrane protein
Alternative names
COX6A, COX6AH, COX6A2, Cytochrome c oxidase polypeptide VIa-heart, Cytochrome c oxidase subunit VIA-muscle, COXVIAH, COX VIa-M