Organization of the human transferrin gene: direct evidence that it originated by gene duplication.

Park, Insoo; Schaeffer, Evelyne; Sidoli, Alessandro; Baralle, Francisco E.; Cohen, Georges N.; Zakin, Mario M.

doi:10.1073/pnas.82.10.3149

Cited by 131 publications

(79 citation statements)

References 24 publications

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“…The intron-exon boundaries correspond to those determined for the chicken transferrin gene (8,19) and conform to the published consensus sequences of splice junctions (28). Clones from the human transferrin gene have been obtained and sequenced (23,32); of the intron positions reported, all are identical to those of the chicken gene and to the 5' and 3' introns described here for the mouse gene.…”

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confidence: 99%

Expression from the transferrin gene promoter in transgenic mice.

et al. 1989

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Transferrin is an iron-binding protein that is expressed as a major product in liver and secreted into the plasma. To study the tissue-specific regulatory regions of this gene, the genomic mouse transferrin (mTf) gene was cloned and characterized by partial sequence analysis and Si nuclease mapping of the transcriptional start site. Fusion genes containing the transferrin gene promoter and 5'-flanking sequences were ligated to the human growth hormone (hGH) gene and used to produce transgenic mice. A deletion construct containing the -581 to +50 region of the transferrin gene was sufficient to direct a high level of liver-specific expression resembling endogenous transferrin gene expression. Deletion to -139 base pairs of 5'-flanking sequence gave a construct which retained liver specificity, but the magnitude of expression decreased severalfold. These results demonstrate the presence of a liver-specific transcriptional element between -139 and +50 and suggest the presence of a distal element between -581 and -139 that can further increase expression. Surprisingly, fusion constructs containing -3 kilobase pairs (kb) of 5'-flanking sequence gave higher levels of mRNA in nonhepatic tissues than did either the -581 or -139 construct. Further studies indicated that the high levels of circulating hGH in these transgenic mice specifically induced the endogenous transferrin and albumin genes in liver and also stimulated the normally low levels of expression of the endogenous transferrin gene in brain, heart, kidney, and muscle. A mutated hGH gene that does not produce active growth hormone was fused to the -3-to +50-kb transferrin sequences to produce the -3-kb mTf-hGX construct. A liver-specific pattern of expression was observed in transgenic mice harboring the -3-kb mTf-hGX construct, and this mutated transgene was shown to be induced four-to sevenfold by either bovine or human growth hormone. These results demonstrate the presence of a growth hormone-responsive element between -3 and +50 kb in the 5'-flanking region of the mTf gene promoter.

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confidence: 99%

Expression from the transferrin gene promoter in transgenic mice.

et al. 1989

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“…The LF gene, together with transferrin and melanoma antigen p97, belongs to the transferrin gene family (Williams, 1982;Park et al, 1985). The three genes present strong homology between the pairs of exons and the splicing pattern, which firmly support the hypothesis that the transferrin gene family originated from a duplication of a common ancestral gene (Masson et al, 1966).…”

Section: Introductionmentioning

confidence: 58%

A novel polymorphism of the lactoferrin gene and its association with milk composition and body traits in dairy goats

Guo

Jiao²,

He³

et al. 2010

Genet. Mol. Res.

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ABSTRACT. Milk composition and body measurement traits, influenced by genes and environmental factors, play important roles in value assessments of efficiency and productivity in dairy goats. Lactoferrin (LF), involved in the efficient expression of protein in milk, is also an anabolic factor in skeletal tissue and a potent osteoblast survival factor. Therefore, it is an important candidate gene for milk composition and body measurement trait selection in marker-assisted selection. We employed PCR-SSCP and DNA sequencing to screen the genetic variations of the LF gene in 549 Chinese dairy goats. A novel single-nucleotide polymorphism (SNP) (G198A in exon II) of the LF gene was detected. The frequencies of the AA genotype were 0.0285 and 0.0261 in GZ and SN populations, respectively. Both populations were found to have low levels of polymorphism and were in Hardy-Weinberg disequilibrium (P < 0.05). We found significant (P < 0.05) associations of the SNP marker with milk protein and acidity in the total population; animals with the AA genotype had higher mean values for milk protein than those with the GA genotype. Animals with genotype AA had higher mean values for withers height than those with genotype GG (P < 0.05). We concluded that this SNP of the LF gene has potential as a genetic marker for milk composition and body traits in dairy goat breeding.

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“…Transferrin is proposed to have arisen through a tandem duplication event in ancestral metazoans resulting in the generation of a bi-lobed protein with two homologous lobes capable of binding two iron atoms (Daugherty and Malik 2012;Park et al 1985). It is generally accepted that the progenitor for Lf arose through a Tf gene duplication event that occurred at time period related to the development of the mammalian lineage (Lambert et al 2005), as this ultimately enabled Lf to develop additional roles without compromising the critical role of Tf in iron homeostasis.…”

Section: Discussionmentioning

confidence: 99%

A comparative, cross-species investigation of the properties and roles of transferrin- and lactoferrin-binding protein B from pathogenic bacteria

Ostan

Morgenthau

et al. 2017

Biochem. Cell Biol.

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Pathogenic bacteria from the families Neisseriaeceae and Moraxellaceae acquire iron from their host using surface receptors that have the ability to hijack iron from the ironsequestering host proteins, transferrin (Tf) and lactoferrin (Lf). The process of acquiring iron from Tf has been well characterized, including the role of the surface lipoprotein, transferrinbinding protein B (TbpB). In contrast, the only well-defined role for the homologue, LbpB, is in its protection against cationic antimicrobial peptides, which is mediated by regions present in some LbpBs that are highly enriched in glutamic or aspartic acid. In this study we compare the Tf -TbpB and the Lf-LbpB interactions and examine the protective effect of LbpB against extracts from human and transgenic mouse neutrophils to gains insights into the physiological roles of LbpB. The results indicate that, in contrast to the Tf-TbpB interaction, Lf-LbpB interaction is sensitive to pH and varies between species. In addition, the results with transgenic mouse neutrophils raise the question of whether there is species specificity in the cleavage of Lf to generate cationic antimicrobial peptides or differences in the potency of peptides derived from mouse and human Lf .

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Organization of the human transferrin gene: direct evidence that it originated by gene duplication.

Abstract: We present the characterization of two overlapping human transferrin genomic clones isolated from a liver DNA library. The two clones represent a total length of 24 kilobase pairs and code for 70% of the protein. The

Cited by 131 publications

References 24 publications

Expression from the transferrin gene promoter in transgenic mice.

Expression from the transferrin gene promoter in transgenic mice.

A novel polymorphism of the lactoferrin gene and its association with milk composition and body traits in dairy goats

A comparative, cross-species investigation of the properties and roles of transferrin- and lactoferrin-binding protein B from pathogenic bacteria

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