Evolution of duplications in the transferrin family of proteins.
ABSTRACT The transferrin family is a group of proteins, defined by conserved amino acid motifs and putative function, found in both vertebrates and invertebrates. Included in this group are molecules known to bind iron, including serum transferrin, ovotransferrin, lactotransferrin, and melanotransferrin (MTF). Additional members of this family include inhibitor of carbonic anhydrase (ICA; mammals), major yolk protein (sea urchins), saxiphilin (frog), pacifastin (crayfish), and TTF-1 (algae). Most family members contain two lobes (N and C) of around 340 amino acids, the result of an ancient duplication event. In this article, we review the known functions of these proteins and speculate as to when the different homologs arose. From multiple-sequence alignments and neighbor-joining trees using 71 transferrin family sequences from 51 different species, including several novel sequences found in the Takifugu and Ciona genome databases, we conclude that melanotransferrins are much older (>670 MY) and more pervasive than previously thought, and the serum transferrin/melanotransferrin split may have occurred not long after lobe duplication. All subsequent duplication events diverged from the serum transferrin gene. The creation of such a large multiple-sequence alignment provides important information and could, in the future, highlight the role of specific residues in protein function.
- SourceAvailable from: Sasimanas Unajak[Show abstract] [Hide abstract]
ABSTRACT: In this study, full-length tilapia transferrin (OnTF) isolated from liver cDNA of Nile tilapia (Oreochromis niloticus) was found to have an open reading frame of 2,091-bp encoding 696 amino acid residues. Two additional amino acids: Gly(369) and Gly(370) were observed compared with the reported Nile tilapia transferrin protein sequence. Pre-mature protein has a predicted molecular weight of 78.2 kDa, while mature protein is 73.28 kDa in size. Comparative sequence analysis with transferrin from other species revealed two major putative iron-binding domains designated as the N-lobe and the C-lobe in accordance with the transferrin protein characteristics. The predicted tertiary structure of tilapia transferrin confirmed the presence of iron and anion-binding sites on both lobes that are conserved among transferrins from other species. Quantitative real-time PCR analysis showed significantly higher expression of tilapia transferrin gene in liver than in other tissues (p < 0.05). Transferrin expression in tilapia experimentally infected with 10(6) and 10(8) colony-forming units mL(-1) of Streptococcus agalactiae was significantly upregulated at 24 and 12 h post-infection (hpi), respectively, and decreased afterward. Iron-deficiency in serum of bacterially infected fish was detected at 48 and 24 hpi, respectively. The expression pattern of the transferrin gene and the iron levels of infected tilapia in this study were consistent with the function of transferrin in innate immunity.Fish Physiology and Biochemistry 04/2014; 40(5). DOI:10.1007/s10695-014-9941-8 · 1.68 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Transferrin is a molecule carrying iron to store and maintain for iron homeostasis of living organisms. In this study, we have purified transferrin, as an iron-binding protein, from the last larval haemolymph of Papilio xuthus by KBr density gradient ultracentrifugation and gel filtration (superose 6 HR) using fast protein liquid chromatography (FPLC) and transferrin containing iron was identified by Ferene S staining. The purified haemolymph transferrin was shown to have molecular mass of 78 and 80 kDa and amino acid composition of transferrin was rich in aspartic acid, valine, leucine and glutamic acid. With immuno-diffusion assay, we confirmed the existence of the transferrin in the haemo-lymph and fat body by detection of visible and clear positive reaction. From the quantitative comparison by rocket immuno-electrophoresis process, the amount of transferrin were increased in the haemolymph of 3 days after pupation and the whole 5 days after pupation. Here, with biochemical and immunohistochemical analysis, we speculate the relationship of transferrin between the physical characteristics and distribution during metamorphosis of P. xuthus.08/2007; 17(8). DOI:10.5352/JLS.2007.17.8.1046
- [Show abstract] [Hide abstract]
ABSTRACT: In a phylogenetic analysis of vertebrate transferrins (TFs), six major clades (subfamilies) were identified: (a) S, the mammalian serotransferrins; (b) ICA, the mammalian inhibitor of carbonic anhydrase (ICA) homologs; (c) L, the mammalian lactoferrins; (d) O, the ovotransferrins of birds and reptiles; (e) M, the melanotransferrins of bony fishes, amphibians, reptiles, birds, and mammals; and (f) M-like, a newly identified TF subfamily found in bony fishes, amphibians, reptiles, and birds. A phylogenetic tree based on the joint alignment of N-lobes and C-lobes supported the hypothesis that three separate events of internal duplication occurred in vertebrate TFs: (a) in the common ancestor of the M subfamily, (b) in the common ancestor of the M-like subfamily, and (c) in the common ancestor of other vertebrate TFs. The S, ICA, and L subfamilies were found only in placental mammals, and the phylogenetic analysis supported the hypothesis that these three subfamilies arose by gene duplication after the divergence of placental mammals from marsupials. The M-like subfamily was unusual in several respects, including the presence of a uniquely high proportion of clade-specific conserved residues, including distinctive but conserved residues in the sites homologous to those functioning in carbonate binding of human serotransferrin. The M-like family also showed an unusually high proportion of cationic residues in the positively charged region corresponding to human lactoferrampin, suggesting a distinctive role of this region in the M-like subfamily, perhaps in antimicrobial defense.Immunogenetics 08/2014; 66(11). DOI:10.1007/s00251-014-0798-x · 2.49 Impact Factor