Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

Metaxin 1 and 2 genes, previously investigated in vertebrates, are shown to be widely distributed among invertebrates. But metaxin 3 is absent. The predicted proteins of the invertebrate metaxins were initially identified by homology with human metaxin 1 and 2 proteins, and by the presence of characteristic GST_Metaxin protein domains. Invertebrate metaxins were revealed for a variety of phyla, including Echinodermata, Cnidaria, Porifera, Chordata, Arthropoda, Mollusca, Brachiopoda, Placozoa, and Nematoda. Metaxins were also found in insects (Arthropoda) of different taxonomic orders: Diptera, Coleoptera, Lepidoptera, Hymenoptera, and Blattodea. Invertebrate and human metaxin 1 proteins have about 41% identical amino acids, while metaxin 2 proteins have about 49% identities. Invertebrate and vertebrate metaxins share the same characteristic protein domains, further strengthening the identification of the invertebrate proteins as metaxins. The domains are, for metaxin 1, GST_N_Metaxin1_like, GST_C_Metaxin1_3, and Tom37. For metaxin 2, they are GST_N_Metaxin2, GST_C_Metaxin2, and Tom37. Phylogenetic trees show that invertebrate metaxin 1 and metaxin 2 proteins are related, but form separate groups. The invertebrate proteins are also closely related to vertebrate metaxins, though forming separate clusters. These phylogenetic results indicate that all metaxins likely arose from a common ancestral sequence. The neighboring genes of the invertebrate metaxin 1 and 2 genes are largely different for different invertebrate species. This is unlike the situation with vertebrate metaxin genes, where, for example, the metaxin 1 gene is adjacent to the thrombospondin 3 gene. The dominant secondary structures predicted for the invertebrate metaxins are alpha-helical segments, with little beta-strand. The conserved pattern of helical segments is the same as that found for vertebrate metaxins 1, 2, and 3.