A novel gene encoding a coiled-coil mitochondrial protein located at the telomeric end of the human MHC Class III region.

The human Major Histocompatibility Complex (MHC) Class III region, which lies in between the MHC Class I and Class II regions on chromosome 6p21.3, contains approximately 60 genes with diverse functions. Using bioinformatics analyses, we identified a novel open reading frame (ORF) in this region, telomeric of BAT1, which we called Mitochondrial Coiled-Coil Domain 1 (MCCD1). The expression of the predicted ORF in a number of human tissues was confirmed by RT-PCR analysis. An orthologue of the MCCD1 gene was identified in the swine MHC in an analogous position, adjacent to pig BAT1. The overall sequence identity between the human and pig MCCD1 proteins is only 65.9%, but their C-terminal domains are highly conserved, showing 92% identity over 53 residues. The MCCD1 gene encodes a short polypeptide (119 amino acids) which contains a putative coiled-coil domain at its highly conserved C terminus and a predicted mitochondrial localisation signal at its N terminus. Transient expression in mammalian cells of MCCD1 fused at its C terminus to either EGFP or the T7-epitope tag showed that this protein is indeed targeted to mitochondria. Finally, we characterised the polymorphism in this gene using denaturing high-performance liquid chromatography (DHPLC) analysis and found that the MCCD1 gene is highly polymorphic containing an average of 1 single nucleotide polymorphism (SNP) every 99 bp. Interestingly, MCCD1 contains four SNPs within the coding region, three of which cause nonsynonymous and nonconservative changes in the amino acid sequence.