Proteins involved in iron metabolism.
| Protein . | Mr . | Gene location . | Structure . | Function . |
|---|---|---|---|---|
| Transferrin | 79,570 | 3q21 | Single chain glycoprotein with two homologous iron-binding sites | Iron-binding transport protein in plasma and extracellular fluid |
| Transferrin receptor | 185,000 | 3q29 | Transmembrane glycoprotein dimer with two transferrin-binding sites | Receptor-mediated endocytosis of ferric transferrin |
| Transferrin receptor 2 | ∼215,000 | 7q22 | Transferrin receptor homologue | Uncertain; possible receptor-mediated endocytosis of ferric transferrin; mutated in a form of non-HFE hemochromatosis |
| Ferritin | 440,000 | H subunit: 11q12; L subunit: 19q13 | Spherical protein shell of 24 subunits, binds up to 4,500 iron atoms | Iron storage; H-subunit has ferroxidase activity; L-subunit catalyzes iron core formation |
| IRP-1, IRP-2 | 90,000 | IRP-1: 9 IRP-2: 15 | Four domain protein; IRP-1 contains a (4Fe-4S) cluster | Translational regulation of synthesis of transferrin receptor, ferritin, and other iron-related proteins |
| HFE | 37,235 | 6p21 | MHC class 1-like glycoprotein; forms heterodimer with β2-microglobulin | Uncertain; the HFE protein-β2-microglobulin heterodimer binds transferrin receptor, reducing its affinity for transferrin |
| DMT1 (also known as DCT1 and NRAMP2) | ∼90,000 | 12q13 | Single chain glycoprotein with 12 (predicted) transmembrane domains | Iron transport protein from gastrointestinal lumen into duodenal enterocyte; from erythroblast endosome to cytoplasm |
| Heme oxygenase 1 (EC 1.14.99.3) | ∼30,000 | 22q12 | Protein with heme site between α-helical folds | Catalytic oxidation of heme to Fe(II), carbon monoxide and biliverdin |
| Fe-ATPase iron transporter | Not known | Not known | Not known | Macrophage intracelullar transmembrane iron transport; coupled with heme oxygenase 1 |
| Ferroportin 1 | 62,000 | 2 | Single-chain glycoprotein with at least 10 transmembrane domains | Iron transport protein at duodenal enterocyte basolateral lumen; macrophage cytoplasm; hepatocyte sinusoidal membrane |
| Ceruloplasmin | 132,000 | 3q21-24 | Single-chain glycoprotein that contains six copper atoms | Probable serum ferroxidase |
| Hephaestin | 155,000 | Xq11-12 | Transmembrane-bound ceruloplasmin homologue | Possible intracellular ferroxidase |
| SFT | (338 amino acids) | 10q21 | Single chain glycoprotein with six (predicted) transmembrane domains | Uncertain; increases cellular uptake of both transferrin-bound and nontransferrin-bound iron |
| Frataxin | ∼18,000 | 9q13 | Mitochondrial protein | Mitochondrial iron homeostasis and respiratory function |
| ABC7 | (752 amino acids) | Xq13 | Mitochondrial inner membrane protein | Possible mitochondrial iron export |
| Abbreviations: IRP, iron regulatory protein; ABC7, ATP-binding cassette 7; MHC, major histocompatibility complex; SFT, stimulator of iron transport; HFE, hemochromatosis gene; DMT1, divalent metal transporter 1. | ||||
| Modified and updated from: Sheth S, Brittenham GM: Genetic disorders affecting proteins of iron metabolism: clinical implications. Ann Rev Med. 51:443-64, 2000. | ||||
| Protein . | Mr . | Gene location . | Structure . | Function . |
|---|---|---|---|---|
| Transferrin | 79,570 | 3q21 | Single chain glycoprotein with two homologous iron-binding sites | Iron-binding transport protein in plasma and extracellular fluid |
| Transferrin receptor | 185,000 | 3q29 | Transmembrane glycoprotein dimer with two transferrin-binding sites | Receptor-mediated endocytosis of ferric transferrin |
| Transferrin receptor 2 | ∼215,000 | 7q22 | Transferrin receptor homologue | Uncertain; possible receptor-mediated endocytosis of ferric transferrin; mutated in a form of non-HFE hemochromatosis |
| Ferritin | 440,000 | H subunit: 11q12; L subunit: 19q13 | Spherical protein shell of 24 subunits, binds up to 4,500 iron atoms | Iron storage; H-subunit has ferroxidase activity; L-subunit catalyzes iron core formation |
| IRP-1, IRP-2 | 90,000 | IRP-1: 9 IRP-2: 15 | Four domain protein; IRP-1 contains a (4Fe-4S) cluster | Translational regulation of synthesis of transferrin receptor, ferritin, and other iron-related proteins |
| HFE | 37,235 | 6p21 | MHC class 1-like glycoprotein; forms heterodimer with β2-microglobulin | Uncertain; the HFE protein-β2-microglobulin heterodimer binds transferrin receptor, reducing its affinity for transferrin |
| DMT1 (also known as DCT1 and NRAMP2) | ∼90,000 | 12q13 | Single chain glycoprotein with 12 (predicted) transmembrane domains | Iron transport protein from gastrointestinal lumen into duodenal enterocyte; from erythroblast endosome to cytoplasm |
| Heme oxygenase 1 (EC 1.14.99.3) | ∼30,000 | 22q12 | Protein with heme site between α-helical folds | Catalytic oxidation of heme to Fe(II), carbon monoxide and biliverdin |
| Fe-ATPase iron transporter | Not known | Not known | Not known | Macrophage intracelullar transmembrane iron transport; coupled with heme oxygenase 1 |
| Ferroportin 1 | 62,000 | 2 | Single-chain glycoprotein with at least 10 transmembrane domains | Iron transport protein at duodenal enterocyte basolateral lumen; macrophage cytoplasm; hepatocyte sinusoidal membrane |
| Ceruloplasmin | 132,000 | 3q21-24 | Single-chain glycoprotein that contains six copper atoms | Probable serum ferroxidase |
| Hephaestin | 155,000 | Xq11-12 | Transmembrane-bound ceruloplasmin homologue | Possible intracellular ferroxidase |
| SFT | (338 amino acids) | 10q21 | Single chain glycoprotein with six (predicted) transmembrane domains | Uncertain; increases cellular uptake of both transferrin-bound and nontransferrin-bound iron |
| Frataxin | ∼18,000 | 9q13 | Mitochondrial protein | Mitochondrial iron homeostasis and respiratory function |
| ABC7 | (752 amino acids) | Xq13 | Mitochondrial inner membrane protein | Possible mitochondrial iron export |
| Abbreviations: IRP, iron regulatory protein; ABC7, ATP-binding cassette 7; MHC, major histocompatibility complex; SFT, stimulator of iron transport; HFE, hemochromatosis gene; DMT1, divalent metal transporter 1. | ||||
| Modified and updated from: Sheth S, Brittenham GM: Genetic disorders affecting proteins of iron metabolism: clinical implications. Ann Rev Med. 51:443-64, 2000. | ||||