COX15
Domain
The N-half (TM1-TM4) and C-half (TM5-TM8) domains are connected by an intracellular loop. Each domain is formed from four-helix bundles and they align in a pseudo twofold symmetry manner. The N-half domain is the substrate heme O binding domain and the C-half domain is the cofactor heme B binding domain.
Function
Catalyzes the second reaction in the biosynthesis of heme A, a prosthetic group of mitochondrial cytochrome c oxidase (CcO) (PubMed:12474143). Heme A is synthesized from heme B by two sequential enzymatic reactions catalyzed by heme O synthase (HOS) and heme A synthase (HAS). HAS catalyzes the conversion of heme O to heme A by two successive hydroxylations of the methyl group at C8, in a reaction that involves matrix ferredoxin and ferredoxin reductase. The first hydroxylation forms heme I, the second hydroxylation results in an unstable dihydroxymethyl group, which spontaneously dehydrates, resulting in the formyl group of heme A (By similarity).
Involvement in disease
Mitochondrial complex IV deficiency, nuclear type 6
MC4DN6
An autosomal recessive multisystem disorder with variable manifestations. Some patients present in the neonatal period with encephalomyopathic features, whereas others present later in the first year of life with developmental regression. Clinical features include microcephaly, encephalopathy, hypertrophic cardiomyopathy, persistent lactic acidosis, respiratory distress, hypotonia and seizures. Serum lactate is increased, and laboratory studies show decreased mitochondrial complex IV protein and activity levels.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Porphyrin-containing compound metabolism; heme A biosynthesis; heme A from heme O: step 1/1.
Sequence Similarities
Belongs to the COX15/CtaA family. Type 2 subfamily.
Tissue Specificity
Predominantly found in tissues characterized by high rates of oxidative phosphorylation (OxPhos), including muscle, heart, and brain.
Cellular localization
- Mitochondrion inner membrane
- Multi-pass membrane protein
Alternative names
Heme A synthase COX15, HAS, Cytochrome c oxidase assembly protein COX15 homolog, COX15