Conservation of the modular structure of complement factor I through vertebrate evolution.
Mammalian complement factor I plays pivotal roles in the regulation of complement activation and generation of important biological activities from C3. The evolutionary origin of factor I has been unclear except with regard to the molecular cloning of factor I from amphibian Xenopus. Here, we report the identification and characterization of factor I cDNA from the liver of the banded houndshark. The deduced amino acid sequence of shark factor I showed a modular organization that was completely identical to that of mammalian factor I, suggesting the functional conservation of factor I throughout vertebrate evolution. Functionally important amino acid residues such as the basic residues at the processing site and the residues at the active site of the serine protease domain are conserved. Repeated sequences composed of 16 amino acids were inserted at a site between the leader peptide and the factor I/membrane attacking complex module in the shark factor I. This repeat is missing from mammalian and amphibian factor I, and the biological significance of the sequence, if any, is not clear at the moment. There was only one copy of the shark factor I gene, and Northern blotting analysis showed that the shark factor I gene was expressed only in the liver among several organs tested. While the lack of functional data does not exclude the possibility that factor I could have a different function, all these facts, together with the earlier reported data suggest the existence of a well developed complement system in cartilaginous fish.
Terado
Tokio
T
Department of Experimental Radiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Nonaka
Mayumi I
MI
Nonaka
Masaru
M
Kimura
Hiroshi
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D017244:Complement Factor I / Q000737:chemistry / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D012754:Sharks / Q000235:genetics* / Q000276:immunology; D014982:Xenopus laevis
D018076:DNA, Complementary; D012313:RNA; D017244:Complement Factor I