IDENTIFICATION OF AN ADDITIONAL MEMBER OF THE CYTOCHROME-C-OXIDASE SUBUNIT VIIA FAMILY OF PROTEINS

We report the cloning, nucleotide sequence, evolutionary analysis, and intracellular localization of SIG81, a silica-induced cDNA from mouse macrophages. The cDNA encodes a 111-amino acid protein with extensive sequence identity with members of the mammalian cytochrome c oxidase subunit VIIa (COX7a) family. A human SIG81 sequence >80% identical wit h the mouse cDNA was deduced from homologous sequences in the human ex pressed tags data base. The deduced aminoterminal region shows feature s common to mitochondrial targeting sequences. A phylogenetic analysis of the carboxyl-terminal domain homologous to COX7a identifies SIG81 as a divergent member of the family with an ancient origin. Southern b lot analysis showed that the mouse genome contains two to three copies of the SIG81 gene. Northern blot analysis revealed that the SIG81 tra nscript is approximately 1 kb and expressed in every tissue tested, wi th higher levels of expression observed in kidney and liver. Antibodie s raised against a glutathione S-transferase SIG81 fusion protein dete cted a 13.5-kDa protein that co-fractionates with mitochondrial locali zed enzymatic activity. Taken together, our data suggest that SIG81 is a novel member of the COX7a family that is constitutively expressed i n mouse cells.