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Copyright ©2009 The WJG Press and Baishideng.
World J Gastroenterol. Oct 7, 2009; 15(37): 4617-4626
Published online Oct 7, 2009. doi: 10.3748/wjg.15.4617
Table 1 Main proteins involved in iron homeostasis in mammals
Protein name (alternative name)AcronymsFunctionLocalization
Divalent metal transporter 1 (divalent cation transporter 1, NRAMP 1 and 2)DMT1Traffics divalent metal ions such as iron, zinc, copper and cobalt across the membrane by a proton coupled mechanismEnterocyte (apical membrane)
DCT1Erythroblast (siderosome)
NRAMP1*Macrophage (plasma membrane, phagocytic vesicles*)
NRAMP2
Hepatocyte
Kidney cells
FerrireductaseDcytbReduction of Fe3+ to Fe2+Enterocyte (apical membrane)
STEAP3*Erythroblast (siderosome*)
Heme carrier protein 1HCP1Putative transporter that traffics heme across the membrane by an unknown mechanismEnterocyte (apical membrane)
Hepatocyte
Kidney cells
Heme oxygenaseAn enzyme that disassembles heme to liberate ironEnterocyte (microsomal fraction)
Macrophages
Ferroportin 1 (Iron regulatory protein 1)FPN 1Transmembrane Fe2+ transporter (exporter)Enterocyte (basolateral membrane)
Ireg1Macrophages
MTP1Hepatocytes
HephaestinHpMembrane-bound multicopper ferroxidase, similar to plasma ceruloplasmin, which oxidizes Fe2+ to Fe3+ to load it onto transferrinEnterocyte (basolateral)
Maintenance of cell-surface localization of ferroportinMacrophage
Hepatocyte?
TransferrinTfPlasma Fe3+ binding proteinPlasma
Ligand for transferrin receptors 1 and 2
Transferrin receptor 1TfR1Cellular uptake of transferrin bound ironUbiquitously expressed
Transferrin receptor 2TfR2Sensor for diferric transferrin; regulates hepcidin expression; may participate in a signaling complex with HFEEnterocyte
Hepatocyte
Erythroblast
MitoferrinSLC25A37Mitochondrial iron importer that plays a critical role in supplying iron to ferrochelatase for insertion in protoporphyrin IX to form hemeErythroblast (mitochondria)
FerritinFtIron storage protein (H and L chains)Enterocyte
Ferroxidase activity (H chain)Erythroblast
Macrophage
Hepatocyte
Myocytes and cardiomyocytes
HemosiderinIron storage protein; breakdown product of ferritin that occurs when iron levels are highMacrophage (lysosomes)
Hepatocytes (lysosomes)
Heme exportersLFLVCR*ATP-independent heme export at the cell membrane* ATP-dependent heme export at the cell membrane** and mitochondrial membrane***Erythroblast*
Bcrp/Abcg2**Ubiquitously expressed**,***
Abcb6***
HFEHFERegulates hepcidin expression, mechanism uncertain; may participate in a signaling complex with TfR2; interacts with TfR1 & β-2-microglobulinEnterocyte
Macrophage
Hepatocyte
HemojuvelinHFE2Acts as a BMP co-receptor to stimulate hepcidin transcriptionHepatocytes
Lipocalin 2Mediates a siderophore-like iron uptake pathway. Its an innate immune response to bacterial infection by sequestrating iron, but its physiologic role in iron absorption is not fully worked outEnterocytes (apical membrane)
Macrophages
Adipocyte
HepcidinHEPIron regulatory hormones, binds ferroportin to cause its internalization and degradationHepatocytes
HAMPAdipocytes (low secretion)
LEAP1Enterocytes?
ErythropoietinEPOUpregulates the expression ferroportin in macrophages, TfR1 in erythroblasts, and DMT1 and hephaestin in enterocytesKidney (interstitial peritubular cells)
Downregulates hepcidin expression in hepatocytes and DMT1 expression in macrophagesHepatocytes (low secretion)