Solute carrier family 40 member 1 (SLC40A1)
The protein contains 571 amino acids for an estimated molecular weight of 62542 Da.
May be involved in iron export from duodenal epithelial cell and also in transfer of iron between maternal and fetal circulation. Mediates iron efflux in the presence of a ferroxidase (hephaestin and/or ceruloplasmin). (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Anatomical structure morphogenesis
Cellular iron ion homeostasis
Endothelium development
Iron ion export across plasma membrane
Iron ion homeostasis
Iron ion transmembrane transport
Lymphocyte homeostasis
Multicellular organismal iron ion homeostasis
Negative regulation of apoptotic process
Positive regulation of transcription by RNA polymerase II
Regulation of transcription from RNA polymerase II promoter in response to iron
Spleen trabecula formation
Transmembrane transport
The reference OMIM entry for this protein is 604653
Solute carrier family 40 (iron-regulated transporter), member 1; slc40a1
Ferroportin 1; fpn1
Iron-regulated transporter 1; ireg1
Solute carrier family 11 (proton-coupled divalent metal ion transporter), member 3, formerly; slc11a3, formerly
CLONING
Defects in iron absorption and utilization lead to iron deficiency and overload disorders. Adult mammals absorb iron through the duodenum, whereas embryos obtain iron through placental transport. Iron uptake from the intestinal lumen through the apical surface of the polarized duodenal enterocytes is mediated by the divalent metal transporter, DMT1 (600523). A second transporter had been postulated to export iron across the basolateral surface to the circulation. Donovan et al. (2000) used positional cloning to identify the gene responsible for the hypochromic anemia of the zebrafish mutant 'weissherbst.' The gene, which they called ferroportin-1 (fpn1), encodes a multiple-transmembrane domain protein expressed in the yolk sac that was a candidate for the elusive iron transporter. Zebrafish ferroportin-1 is required for the transport of iron from maternally-derived yolk stores to the circulation and functions as an iron exporter when expressed in Xenopus oocytes. Donovan et al. (2000) isolated mouse and human ferroportin-1 cDNAs by RT-PCR of liver and placenta, respectively. Human ferroportin-1 is a protein of 571 amino acids. A conserved sequence, predicted to form a hairpin-loop structure typical of iron response elements (IREs), was identified in the 5-prime untranslated region of the cDNAs from all 3 species. Northern blot analysis showed the highest level of expression in human placenta, liver, spleen, and kidney. In mouse, primitive erythroblasts derived from the blood islands do not express ferroportin-1, whereas the trophoblast cells of the inner placenta express high levels of ferroportin-1. In the human placenta, ferroportin-1 protein was primarily expressed in a basal location within the syncytiotrophoblasts, suggesting that it transports iron from mother to embryo. Mammalian ferroportin-1 is also expressed at the basolateral surface of duodenal enterocytes. On the basis of basolateral expression pattern of ferroportin-1 in mammalian enterocytes and the implication that ferroportin-1 is required for intestinal iron absorption and iron transport in zebrafish, Donovan et al. (2000) suggested that the protein is probably involved in iron export from enterocytes in mammals. Iron absorption by the duodenal mucosa is initiated by uptake of ferrous Fe(II) iron across the brush border membrane and culminates in transfer of the metal across the basolateral membrane to the portal vein circulation by an unknown mechanism. Using a subtractive cloning strategy and PCR analysis, McKie et al. (2000) isolated mouse and human duodenal cDNAs encoding FPN1, which they called iron-regulated transporter-1 (IREG1). The IREG1 protein contains 10 transmembrane domains and is localized to the basolateral membrane of polarized epithelial cells. IREG1 mRNA and protein expression are increased under conditions of increased iron absorption, and the 5-prime untranslated region of the IREG1 mRNA contains a functional IRE.MAPPING
By FISH, Haile (2000) mapped the SLC40A1 gene to human chromosome 2q32 and mouse chromosome 1B.GENE FUNCTION
McKie et al. (2000) found that IREG1 stimulated iron efflux following expression in Xenopus oocytes. They concluded that IREG1 represents the long-sought duodenal iron export protein and is upregulated in the iron overload disease hereditary hemochromatosis (235200). Nemeth et al. (2004) reported that hepcidin (606464) bound to ferroportin in tissue culture cells. After binding, fer ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604653 was added.