Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new inherited disorder of iron metabolism, hereafter called "the ferroportin disease," is increasingly recognized worldwide. The disorder is due to pathogenic mutations in the SLC40A1 gene encoding for a main iron export protein in mammals, ferroportin1/IREG1/MTP1, and it was originally identified as an autosomal-dominant form of iron overload not linked to the hemochromatosis (HFE) gene. It has distinctive clinical features such as early increase in serum ferritin in spite of low-normal transferrin saturation, progressive iron accumulation in organs, predominantly in reticuloendothelial macrophages, marginal anemia with low tolerance to phlebotomy. Ferroportin mutations have been reported in many countries regardless of ethnicity. They may lead to a loss of protein function responsible for reduced iron export from cells, particularly reticuloendothelial cells. Now, the disorder appears to be the most common cause of hereditary iron overload beyond HFE hemochromatosis.
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PMID:The ferroportin disease. 1475 27

Ferroportin 1 (FPN1; aka MTP1, IREG1, and SLC40A1), which was originally identified as a basolateral iron transporter crucial for nutritional iron absorption in the intestine, is expressed in airway epithelia and upregulated when these cells are exposed to iron. Using immunofluorescence labeling and confocal microscopic imaging techniques, we demonstrate that in human and rodent lungs, FPN1 localizes subcellularly to the apical but not basolateral membrane of the airway epithelial cells. The role of airway epithelial cells in iron mobilization in the lung was studied in an in vitro model of the polarized airway epithelium. Normal human bronchial epithelial cells, grown on membrane supports until differentiated, were exposed to iron, and the efficiency and direction of iron transportation were studied. We found that these cells can efficiently take up iron across the apical but not basolateral surface in a concentration-dependent manner. Most of the iron taken up by the cells is then released into the medium within 8 h in the form of less reactive protein-bound complexes including ferritin and transferrin. Interestingly, iron release also occurred across the apical but not basolateral membrane. Our findings indicate that FPN1, depending on its subcellular location, could have distinct functions in iron homeostasis in different cells and tissues. Although it is responsible for exporting nutrient iron from enterocytes to the circulation in the intestine, it could play a role in iron detoxification in airway epithelial cells in the lung.
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PMID:Apical location of ferroportin 1 in airway epithelia and its role in iron detoxification in the lung. 1574 37

Ferroportin disease is caused by mutation of one allele of the iron exporter ferroportin (Fpn/IREG1/Slc40a1/MTP1). All reported human mutations are missense mutations and heterozygous null mutations in mouse Fpn do not recapitulate the human disease. Here we describe the flatiron (ffe) mouse with a missense mutation (H32R) in Fpn that affects its localization and iron export activity. Similar to human patients with classic ferroportin disease, heterozygous ffe/+ mice present with iron loading of Kupffer cells, high serum ferritin, and low transferrin saturation. In macrophages isolated from ffe/+ heterozygous mice and through the use of Fpn plasmids with the ffe mutation, we show that Fpn(ffe) acts as a dominant negative, preventing wild-type Fpn from localizing on the cell surface and transporting iron. These results demonstrate that mutations in Fpn resulting in protein mislocalization act in a dominant-negative fashion to cause disease, and the Fpn(ffe) mouse represents the first mouse model of ferroportin disease.
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PMID:The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease. 1728 7