FAXC Proteins of Vertebrates and Invertebrates: Relationship to Metaxin Proteins

Abstract

FAXC proteins of vertebrates and invertebrates are shown to possess structural features similar to the metaxins, and can therefore be categorized as metaxin-like proteins. A variety of vertebrate and invertebrate species were found to encode FAXC (Failed Axon Connections) proteins. These are predicted proteins. Among the vertebrate species are human, mouse, zebrafish, and Xenopus. For invertebrates, FAXC proteins were most common in phyla that include Mollusca, Arthropoda, Cnidaria, and Placozoa. The presence of characteristic GST_N_Metaxin and GST_C_Metaxin protein domains was an important criterion in identifying the FAXCs as metaxin-like. In addition, the Tom37 domain was frequently found, especially in vertebrates. Also important was the possession of segments of -helical secondary structure in a pattern of eight helices like that of metaxin 1 and other metaxins. Both the domain structures and -helical structures are characteristic metaxin-like features. But alignment of protein sequences of both vertebrate and invertebrate FAXCs with metaxin proteins demonstrated that FAXCs and metaxins have low percentages of identical amino acids, about 20%. Therefore, FAXCs and metaxins are related, but are not the same protein. As revealed by phylogenetic analysis, vertebrate FAXCs and vertebrate metaxins 1, 2, and 3 constitute separate but related groups of proteins. Distinct phylogenetic groups were also observed for invertebrate FAXCs and invertebrate metaxins 1 and 2. The FAXC genes have neighboring genes that differ from the neighboring genes of metaxins. For vertebrates, the genes adjacent to FAXC genes are highly conserved. For invertebrates, the genes that neighbor FAXC genes are not the same as for vertebrates, but are conserved among different invertebrates. Invertebrates can have multiple FAXC genes, up to at least 12 or 13 genes. In some cases, the multiple FAXC genes exist as a cluster of genes in close proximity.