This is a family of integral membrane proteins. CtaA (also known as heme A synthase) is required for cytochrome aa3 oxidase assembly in Bacillus subtilis []. COX15 is required for cytochrome c oxidase assembly [], and is involved in the synthesis of heme A [, , ]. COX15 forms highly stable complexes through hydrophobic interactions, and this multimerization is evolutionarily conserved, independent of heme levels and heme a synthase catalytic activity. There are four conserved histidine residues critical for eukaryotic heme a synthase activity []. Mutations of COX15 are associated with fatal infantile hypertrophic cardiomyopathy and the neurological disorder Leigh syndrome, due to impaired stability (S344P) or catalytic function (R217W).In some cases, heme A synthase is found fused to protoheme IX farnesyltransferase, an enzyme that converts protoheme IX to heme O.
