Antigenic protein specific for C3H strain mouse is a mitochondrial stress-70 protein

Cells derived from C3H strain mouse produce an antigenic protein (CSA) specific for this strain [Kusakabe, M., et al. (1988) J. Cell Biol. 107, 257-265]. To examine the molecular basis of CSA, cDNA cloning of the antigenic protein was carried out. The deduced amino acid sequence demonstrates that CSA is the same protein as peptide-binding protein 74 (PBP74), a novel member of the stress-70 family. However, comparison of the PBP74/CSA sequences between C3H/HeN and BALB/c strain mice reveals the substitution of two amino acids in the substrate-recognition domain of the stress-70 protein. Western blot analysis indicates that one out of these two residues, arginine at residue 578 in the PBP74/CSA sequence of C3H mouse, contributes to the immunogenicity of CSA. Moreover, the subcellular localization of PBP74/CSA in mitochondria is also demonstrated by immunohistochemical analysis using anti-CSA monoclonal antibody. Thus, it is interesting that a genetic marker sequence in mice is located on the gene encoding a mitochondrial stress-70 protein.