Evolution of duplications in the transferrin family of proteins

Department of Biology, Chatham College, Woodland Road, Pittsburgh, PA 15232, USA.
Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology (Impact Factor: 1.55). 02/2005; 140(1):11-25. DOI: 10.1016/j.cbpc.2004.09.012
Source: PubMed


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.

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    • "Comprehensive studies on transferrin indicate that most of the C-terminal domains from insect transferrins lack the ability to bind to iron since functionally important amino acid residues have been substituted by different amino acids; however, the transferrins from some insects including Blaberus discoidalis (Jamroz et al., 1993), the termite Mastotermes darwiniensis (Thompson et al., 2003), the beetle Apriona germari (Lee et al., 2006), and Protaetia brevitarsis (Kim et al., 2008) carry bilobed iron-binding features similar to those present in mammalian transferrins. In addition, some transferrinlike molecules have been documented to contain one lobe (single-lobed transferrins) or three lobes (trilobed transferrins) with iron (III) binding ability (Lambert et al., 2005b). Diverse structural features have been observed among the transferrin-like proteins identified to date. "
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    ABSTRACT: The basic function of transferrin is to bind iron (III) ions in the medium and to deliver them to the locations where they are required for metabolic processes. It also takes part in the host immune defense mainly via its ability to bind to iron (III) ions. Hence, transferrin is also identified as an important acutephase protein in host immunity. Abalones are major shellfish aquaculture crops that are susceptible to a range of marine microbial infections. Since transferrin is known to be a major player in innate immunity, in the present study we sought to identify, and molecularly and functionally characterize a transferrinlike gene from disk abalone (Haliotis discus discus) named as AbTrf. AbTrf consisted of a 2187-bp open reading frame (ORF) which encodes a 728 amino acid (aa) protein. The putative amino acid sequence of AbTrf harbored N- and C-terminal transferrin-like domains, active sites for iron binding, and conserved cysteine residues. A constitutive tissue specific AbTrf expression pattern was detected by qPCR in abalones where mantle and muscle showed high AbTrf expression levels. Three immune challenge experiments were conducted using Vibrio parahaemolyticus, Listeria monocytogenes and LPS as stimuli and, subsequently, AbTrf mRNA expression levels were quantified in gill and hemocytes in a time-course manner. The mRNA expression was greatly induced in both tissues in response to both challenges. Evidencing the functional property of transferrins, recombinant AbTrf N-terminal domain (AbTrf-N) showed dose-dependent iron (III) binding activity detected by chrome azurol S (CAS) assay system. Moreover, recombinant AbTrf-N could significantly inhibit the growth of iron-dependent bacterium, Escherichia coli in a dose-dependent manner. However, AbTrf-N was unable to show any detectable bacteriostatic activity against iron-independent bacterium Lactobacillus plantarum (L. plantarum) even at its highest concentration. Collectively, our results suggest that AbTrf might play a significant role in the host innate immunity, possibly by withholding iron from pathogens.
    Developmental & Comparative Immunology 11/2015; 53(1):222-233. DOI:10.1016/j.dci.2015.07.013 · 2.82 Impact Factor
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    • "Tf is a very highly conserved protein found from bacteria to mammals, including algae [11] [12] [13] [14]. Interestingly, Tf is absent in nematodes [15], and unfortunately there is no evidence of the presence of this protein in parasitic protozoa. "
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    ABSTRACT: Iron is the fourth most abundant element on Earth and the most abundant metal in the human body. This element is crucial for life because almost all organisms need iron for several biological activities. This is the case with pathogenic organisms, which are at the vanguard in the battle with the human host for iron. The latest regulates Fe concentration through several iron-containing proteins, such as transferrin. The transferrin receptor transports iron to each cell that needs it and maintains it away from pathogens. Parasites have developed several strategies to obtain iron as the expression of specific transferrin receptors localized on plasma membrane, internalized through endocytosis. Signal transduction pathways related to the activation of the receptor have functional importance in proliferation. The study of transferrin receptors and other proteins with action in the signaling networks is important because these proteins could be used as therapeutic targets due to their specificity or to differences with the human counterpart. In this work, we describe proteins that participate in signal transduction processes, especially those that involve transferrin endocytosis, and we compare these processes with those found in T. brucei, T. cruzi, Leishmania spp., and E. histolytica parasites.
    06/2015; 2015:1-12. DOI:10.1155/2015/641392
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    • "Members of the transferrin family include serotransferrin (STF) that is found in mammalian blood, ovotransferrin (OTF) encoded by the avian egg white, lactotransferrin (LTF) found in most milk and tears, saliva and other secretory fluids, and melanotransferrin (MTF) isolated from melanoma cells. Functions of transferrin include iron transport from plasma to target cells and regulation of iron levels in biological fluids of organisms (Lambert et al. 2005a). Aquatic animals require certain essential elements for normal life processes, e.g., Fe, Mn, Cu, Co and Zn (Santosh 2002). "
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    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 · 1.62 Impact Factor
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