Metaxin 3 is a Highly Conserved Vertebrate Protein Homologous to Mitochondrial Import Proteins and GSTs

Metaxin 3 genes are shown to be widely conserved in vertebrates, including mammals, birds, fish, amphibians, and reptiles. Metaxin 3 genes, however, are not found in invertebrates, plants, and bacteria. The predicted metaxin 3 proteins were identified by their homology to the metaxin 3 proteins encoded by zebrafish and Xenopus cDNAs. Further evidence that they are metaxin proteins was provided by the presence of GST_N_Metaxin, GST_C_Metaxin, and Tom37 protein domains, and the absence of other major domains. Alignment of human metaxin 3 and human metaxin 1 predicted amino acid sequences showed 45% identities, while human metaxin 2 had 23% identities. These results indicate that metaxin 3 is a distinct metaxin. A wide variety of vertebrate species--including human, zebrafish, Xenopus, dog, shark, elephant, panda, and platypus--had the same genes adjacent to the metaxin 3 gene. In particular, the thrombospondin 4 gene (THBS4) is next to the metaxin 3 gene (MTX3). By comparison, the thrombospondin 3 gene (THBS3) is next to the metaxin 1 gene (MTX1). Phylogenetic analysis showed that metaxin 3, metaxin 1, and metaxin 2 protein sequences formed separate clusters, but with all three metaxins being derived from a common ancestor. Alpha-helices dominate the predicted secondary structures of metaxin 3 proteins. Little beta-strand is present. The pattern of 9 helical segments is also found for metaxins 1 and 2.