Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on curation of immunofluorescence data
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
A novel mammalian iron-regulated protein involved in intracellular iron metabolism.
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Original discovery of MTP1/ferroportin identifying it as an iron-regulated protein involved in iron metabolism.
"We have isolated and characterized a novel iron-regulated gene that is homologous to the divalent metal transporter 1 family of metal transporters"
A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation.
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Identified IREG1 (ferroportin) at the basolateral membrane of duodenal enterocytes
"We describe here the isolation and characterization of a novel cDNA (Ireg1) encoding a duodenal protein that is localized to the basolateral membrane of polarized epithelial cells"
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Implicated in transfer of dietary iron to the circulation
"We conclude that IREG1 represents the long-sought duodenal iron export protein"
Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).
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V162del mutation causes hemochromatosis type 4
"A 3-base pair deletion in exon 5 of the ferroportin 1 gene (SLC11A3) predicting Val162 deletion was found in affected members"
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Established genetic evidence for ferroportin role in iron export
"These results indicate that this extracellular cluster is functionally important for iron transport, and its disruption leads to iron overload"
In vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations.
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Demonstrated ferrous iron (Fe2+) transport activity
"expression of human FPN in a human cell line results in an iron deficiency because of a 3-fold increased export of iron"
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Characterized disease mutations A77D and G490D showing loss of function
"FPN mutations A77D, V162delta, and G490D that are associated with a typical pattern of disease in vivo cause a loss of iron export function in vitro"
Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic beta-cells.
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Co-localization of ferroportin with hephaestin
"In addition to its expression in the same cells as Hp, ferroportin was also localized to the ductal cells of the exocrine pancreas"
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Basolateral membrane localization in multiple tissues
"previous immunocytochemical studies in rat, mouse, and human gut tissues localized Hp to the basolateral membranes of the duodenal enterocytes"
Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease.
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APP interacts with ferroportin to facilitate iron export
"Like ceruloplasmin, APP catalytically oxidizes Fe(2+), loads Fe(3+) into transferrin, and has a major interaction with ferroportin"
Hepcidin-induced endocytosis of ferroportin is dependent on ferroportin ubiquitination.
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Hepcidin binding triggers ferroportin ubiquitination
"Hepcidin binding caused rapid ubiquitination of ferroportin in cell lines overexpressing ferroportin and in murine bone marrow-derived macrophages"
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Ubiquitination required for endocytosis and degradation
"Our study demonstrates that ubiquitination is the functionally relevant signal for hepcidin-induced ferroportin endocytosis"
sAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin.
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Soluble APP stabilizes ferroportin at the membrane
"the stimulation of efflux supported by this peptide and by sAPPα is due to their stabilization of the ferrous iron exporter, ferroportin (Fpn), in the plasma membrane"
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Mechanism of iron export regulation in brain
"in stabilizing Fpn via the targeting due to the FTP sequence, sAPP will increase the flux of iron into the cerebral interstitium"
Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin.
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Mapped hepcidin binding site on ferroportin
"hepcidin binding occurred within the central cavity of Fpn"
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Identified key residues N144, Y501, D504 required for binding
"All clinical mutants were functionally resistant to hepcidin as a consequence of either impaired hepcidin binding or impaired hepcidin-dependent ubiquitination despite intact hepcidin binding"
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N144D shows complete loss of hepcidin binding
"mutations that caused ubiquitination-resistance were positioned at helix-helix interfaces, likely preventing the hepcidin-induced conformational change"
Manganese transport and toxicity in polarized WIF-B hepatocytes.
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Ferroportin localized to basolateral membrane in hepatocytes
"Fpn and ZIP14 localize to basolateral domains"
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Evidence that Mn2+ is not a physiological substrate
"Hepcidin reduced levels of Fpn in WIF-B cells, clearing Fpn from the cell surface, but Mn efflux was unaffected"
Ferroportin disease mutations influence manganese accumulation and cytotoxicity.
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Characterized disease mutations affecting localization and function
"disease mutations interfere with the role of Fpn in controlling Mn levels as well as the stability of Fpn"
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G80S, D157G lose cell surface localization
"Hemochromatosis is a frequent genetic disorder, characterized by the accumulation of excess iron across tissues"
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N144H/T show hepcidin resistance
"These results define the function of Fpn as an exporter of both iron and Mn"
Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms.
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Cryo-EM structure of ferroportin with and without hepcidin
"determine cryogenic electron microscopy structures of ferroportin in lipid nanodiscs, both in the apo state and in complex with hepcidin and the iron mimetic cobalt"
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Revealed iron-binding sites and hepcidin binding as molecular cork
"Hepcidin binds ferroportin in an outward-open conformation and completely occludes the iron efflux pathway"
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12-TM topology confirmed
"hepcidin directly contacts the divalent metal in the ferroportin C domain"
Apo- and holo-transferrin differentially interact with hephaestin and ferroportin in a novel mechanism of cellular iron release regulation.
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Ferroportin, hephaestin, and transferrin form functional complex
"holo-Tf directly interacts with ferroportin, whereas apo-Tf directly interacts with hephaestin"
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Holo-transferrin promotes ferroportin degradation
"We demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway"
SLC40A1:HEPH:6Cu2+ transports Fe2+ from cytosol to extracellular region
Defective CP does not oxidise Fe2+ to Fe3+
Defective SLC40A1 does not transport Fe2+ from cytosol to extracellular region
Defective SLC40A1 does not transport Fe3+ from extracellular region to cytosol
SLC40A1:CP:6Cu2+ transports Fe2+ from cytosol to extracellular region
SLC40A1:CP:6Cu2+ oxidises Fe2+ to Fe3+
SLC40A1:HEPH:6Cu2+ oxidises 4Fe2+ to 4Fe3+