Recombinant Human Cytochrome c oxidase subunit 5A, mitochondrial (COX5A)

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 using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix

Subcellular Location

Mitochondrion inner membrane (Peripheral membrane protein)

Disease Association

Mitochondrial complex IV deficiency, nuclear type 20 (MC4DN20) : An autosomal recessive mitochondrial disorder with onset in early infancy. MC4DN20 is characterized by pulmonary arterial hypertension, poor feeding, failure to thrive, hypotonia, delayed development, increased serum lactate and metabolic acidosis. Death in infancy occurs due to cardiorespiratory failure. Patient tissues show variably decreased levels and activity of mitochondrial respiratory complex IV. [The disease may be caused by variants affecting the gene represented in this entry]

Subunit

Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and COXFA4, which are encoded in the nuclear genome (PubMed:30030519). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695). Interacts with AFG1L (PubMed:26759378). Interacts with RAB5IF (PubMed:31536960)

Pathway

Energy metabolism; oxidative phosphorylation

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