Mouse anti-Human/Mouse/Rat COX4I1 Monoclonal Antibody

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 (Single-pass membrane protein)

Disease Association

Mitochondrial complex IV deficiency, nuclear type 16 (MC4DN16) : An autosomal recessive mitochondrial disorder with onset in infancy and variable manifestations. MC4DN16 features include feeding difficulties, poor overall growth, short stature, microcephaly, developmental regression, severe hypotonia, and seizures. Cerebral and cerebellar atrophy, and abnormal lesions in the basal ganglia can be observed on brain imaging. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Ubiquitous

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 PHB2; the interaction decreases in absence of SPHK2 (By similarity). Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding. Interacts with IRGC (By similarity)

Pathway

Energy metabolism; oxidative phosphorylation

• Zeviani M. et al. Isolation of a cDNA clone encoding subunit IV of human cytochrome c oxidase. — Gene (1987)
• Lomax M.I. et al. Novel use of a chimpanzee pseudogene for chromosomal mapping of human cytochrome c oxidase subunit IV. — Gene (1990)
• Park S.J. et al. PubMed: CI-FRGG9O0M62H8N (OCT-)
• Yu W. et al. PubMed: CI-2GVSOO0IJ2N0B (MAR-)
• Bachman N.J. et al. The COX4 gene and a linked gene, COX4AL, are controlled by a bidirectional promoter. (MAY-)
• Poyau A. et al. COX4, the human cytochrome c oxidase subunit IV gene. (AUG-)
• Kalnine N. et al. Cloning of human full-length CDSs in BD Creator(TM) system donor vector. (OCT-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)