Article

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

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.

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    • "The original Tf ancestor had only a single lobe, and the first duplication event resulted in tandem genes, which later fused to form an ancestral, double-lobed Tf (Williams et al., 1982). Over time, the lobes have been deleted (single lobe protein) and further duplicated (the triple-lobed molecules in algae), suggesting that Tfs have adapted over the years in a variety of ways based on the unique physiological demands of different organisms (Lambert et al., 2005); thus, the tracing of original events can be challenging. Both LTf and ICA originated from relatively recent but separate duplications of the STf gene, and multiple copies of the MTf gene may show lethal dominance; therefore, duplications cannot survive (Nakamasu et al., 1999). "
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    ABSTRACT: Transferrins have been identified in animals and green algae, and they consist of a family of evolutionarily related proteins that play a central role in iron transport, immunity, growth and differentiation. This study assessed the transferrin genes among 100 genomes from a wide range of animal and plant kingdoms. The results showed that putative transferrins were widespread in animals, but their gene quantity and type differ greatly between animal groups. Generally, Mammalia possess abundant transferrin genes, whereas Trematoda contain few ones. Melanotransferrin and serotransferrin are widely distributed in vertebrates, while melanotransferrin-like and transferrin-like 1 are frequent in invertebrates. However, only a few plant species detected putative transferrins, and a novel transferrin member was first uncovered in Angiospermae and Pteridophyta. The structural comparison among transferrin family members revealed seven very well-repeated and conserved characteristic motifs, despite a considerable variation in the overall sequences. The phylogenetic analysis suggested that gene duplication, gene loss and horizontal transfer contributed to the diversification of transferrin family members, and their inferred evolutionary scenario was proposed. These findings help to the understanding of transferrin distribution, characteristic motifs and residues, and evolutionary process.
    Full-text · Article · Mar 2016 · Comparative Biochemistry and Physiology Part D Genomics and Proteomics
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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.
    Full-text · Article · Nov 2015 · Developmental & Comparative Immunology
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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.
    Full-text · Article · Jun 2015
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