InterPro domain: IPR003780

In some cases, heme A synthase is found fused to protoheme IX farnesyltransferase, an enzyme that converts protoheme IX to heme O.

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 [ 1 ]. COX15 is required for cytochrome c oxidase assembly [ 2 ], and is involved in the synthesis of heme A [ 3 , 4 , 5 ]. 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 [ 6 ]. 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).

1. Isolation and sequence of ctaA, a gene required for cytochrome aa3 biosynthesis and sporulation in Bacillus subtilis. J. Bacteriol. 171, 4967-78
2. COX15 codes for a mitochondrial protein essential for the assembly of yeast cytochrome oxidase. J. Biol. Chem. 272, 19088-94
3. Mutations in COX15 produce a defect in the mitochondrial heme biosynthetic pathway, causing early-onset fatal hypertrophic cardiomyopathy. Am. J. Hum. Genet. 72, 101-14
4. Involvement of mitochondrial ferredoxin and Cox15p in hydroxylation of heme O. FEBS Lett 492, 133-8
5. Analysis of Oligomerization Properties of Heme a Synthase Provides Insights into Its Function in Eukaryotes. J Biol Chem 291, 10411-25