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Application of computer methods for revelation of the role of CP-like copper-containing ferroxidases in iron metabolism

Phylogenetic analysis of the cloned fragments 1 and 2 of putative ceruloplasmin receptor was made. Fragment 1 is highly homologous to all known Cp-like ferroxidases. It contains mononuclear ferroxidase center that is highly conservative and similar to all analogous centers of Cp-like ferroxidases. Fragment 2 nucleotide sequence has near 70 percent of homology to exon 16 of Cp gene, but has no amino acid homology. It has a distant resemblance with transmembrane domains of other membrane bound Cp-like ferroxidases. Their amphipatic profiles are similar. Sequence with 90 percent of homology to fragment 2 was found in the published human genome on Internet site NCBI. It is localized on chromosome 3 on the complementary strand in the region of exon 16 of Cp gene. The interspecies comparison of Cp-mRNA was made for evaluation of biological significance of secondary structure of the area between 2670-2820 b.p. The level of synonymous substitutions is essentially lower and the ratio of synonymous to non-synonymous substitutions is essentially higher in this region, than in the whole coding region of Cp. This data show the role of secondary structure of the nucleotide sequence on the border between exons 15 and 16 in post transcriptional processing of pre- mRNA Cp.