TF (serotransferrin) is a secreted bilobed plasma glycoprotein, produced mainly by the liver, that reversibly binds two ferric (Fe3+) ions (each lobe one Fe3+ with a bicarbonate anion) and transports iron through the blood. Iron-loaded (holo) transferrin binds the transferrin receptors TfR1 (TFRC) and TfR2 at the cell surface and is internalized via clathrin-coated pits into early/recycling endosomes, where acidification releases the iron; apo-transferrin then recycles to the surface. Transferrin is central to systemic iron homeostasis and, by keeping plasma iron sequestered, contributes to nutritional immunity against pathogens.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005506 iron ion binding | IEA GO_REF:0000117 | MODIFY | Summary: Iron ion binding (ARBA). Reason: True but general; transferrin specifically binds ferric iron (Fe3+). Proposed replacements: ferric iron binding Supporting Evidence: file:human/TF/TF-uniprot.txt bind two Fe(3+) ions |
| GO:0005515 protein binding | IPI PMID:14691533 Mechanism for multiple ligand recognition by the human trans... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:16271884 The molecular mechanism for receptor-stimulated iron release... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:16354665 Release of the soluble transferrin receptor is directly regu... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:22327295 Structural basis for iron piracy by pathogenic Neisseria. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:22327295 Structural basis for iron piracy by pathogenic Neisseria. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:22343719 The structural basis of transferrin sequestration by transfe... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:29302006 Transferrin receptor 1 is a reticulocyte-specific receptor f... | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding (IPI), mostly high-throughput interactome partners. Reason: GO:0005515 is uninformative about molecular function; removal follows the protein-binding policy and does not dispute the interactions. Transferrin's informative binding is captured by transferrin receptor binding. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | HDA PMID:23580065 Shotgun proteomics reveals specific modulated protein patter... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IDA PMID:37277838 Apo- and holo-transferrin differentially interact with hepha... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IDA PMID:9990067 Association of HFE protein with transferrin receptor in cryp... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | NAS PMID:14718574 The human plasma proteome: a nonredundant list developed by ... | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-482770 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5691150 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8866277 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-917807 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-917814 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-917839 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-917888 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-917987 | ACCEPT | Summary: Extracellular region - transferrin is a secreted plasma protein. Reason: Core location; transferrin is secreted into plasma and acts extracellularly. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005768 endosome | IEA GO_REF:0000107 | MODIFY | Summary: Endosome (ortholog transfer). Reason: Correct but general; the transferrin cycle specifically involves early and recycling endosomes (both annotated). Proposed replacements: early endosome Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0005769 early endosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Early endosome (transferrin cycle - iron release compartment). Reason: Iron is released from transferrin in early/sorting endosomes; a cycle location, non-core. |
| GO:0005769 early endosome | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Early endosome (transferrin cycle - iron release compartment). Reason: Iron is released from transferrin in early/sorting endosomes; a cycle location, non-core. |
| GO:0005769 early endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Early endosome (transferrin cycle - iron release compartment). Reason: Iron is released from transferrin in early/sorting endosomes; a cycle location, non-core. |
| GO:0005770 late endosome | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Late endosome. Reason: Transferrin-receptor pool observed in late endosomes in trophoblast cells; a cycle location, non-core. Supporting Evidence: PMID:15880641 Transferrin receptor co-localizes and interacts with the hemochromatosis factor (HFE) |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Endoplasmic reticulum lumen (secretory pathway). Reason: Transferrin transits the ER lumen during secretion; a biosynthetic location. Supporting Evidence: Reactome:R-HSA-8952289 FAM20C phosphorylates FAM20C substrates |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane (is_active_in) - receptor-bound transferrin at the cell surface. Reason: Transferrin is a soluble ligand that associates with the plasma membrane only via its receptor; a functional surface pool, non-core. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:0005905 clathrin-coated pit | IDA PMID:12857860 Myo6 facilitates the translocation of endocytic vesicles fro... | KEEP AS NON CORE | Summary: Clathrin-coated pit (transferrin cycle). Reason: Receptor-bound transferrin concentrates in clathrin-coated pits before endocytosis; non-core. Supporting Evidence: PMID:12857860 endocytic vesicles |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Clathrin-coated pit (ortholog transfer). Reason: Receptor-bound pool during endocytosis; non-core. |
| GO:0006826 iron ion transport | IBA GO_REF:0000033 | ACCEPT | Summary: Iron ion transport - the core physiological role of transferrin. Reason: Transferrin transports iron through the blood to sites of utilization. Supporting Evidence: file:human/TF/TF-uniprot.txt responsible for the transport of iron |
| GO:0006826 iron ion transport | IDA PMID:9465039 The hemochromatosis gene product complexes with the transfer... | ACCEPT | Summary: Iron ion transport demonstrated in the HFE/transferrin receptor study. Reason: Core iron-transport function. Supporting Evidence: PMID:9465039 transferrin receptor |
| GO:0006826 iron ion transport | IEA GO_REF:0000002 | ACCEPT | Summary: Iron ion transport (InterPro). Reason: Core function. Supporting Evidence: file:human/TF/TF-uniprot.txt responsible for the transport of iron |
| GO:0006826 iron ion transport | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | ACCEPT | Summary: Iron ion transport (genetic interaction with TfR2/HFE). Reason: Core function. Supporting Evidence: PMID:18353247 cellular uptake of transferrin-bound iron |
| GO:0006879 intracellular iron ion homeostasis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Intracellular iron ion homeostasis. Reason: Transferrin delivers iron affecting cellular iron balance; a downstream homeostatic role. |
| GO:0006879 intracellular iron ion homeostasis | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: Intracellular iron ion homeostasis (genetic interaction). Reason: Downstream homeostatic role of iron delivery; non-core. Supporting Evidence: PMID:18353247 cellular uptake of transferrin-bound iron |
| GO:0007166 cell surface receptor signaling pathway | IDA PMID:9465039 The hemochromatosis gene product complexes with the transfer... | KEEP AS NON CORE | Summary: Cell surface receptor signaling pathway. Reason: Transferrin binding engages its receptor; a surface-receptor interaction, peripheral to iron transport. Supporting Evidence: PMID:9465039 transferrin receptor |
| GO:0008198 ferrous iron binding | IDA PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | UNDECIDED | Summary: Ferrous iron binding (IDA). Reason: Transferrin canonically binds ferric (Fe3+) iron; a ferrous-iron-binding activity is atypical and the supporting paper is abstract-only in the cache, so the evidence cannot be adjudicated. Left UNDECIDED per the standing rule rather than overruling an experimental annotation. |
| GO:0008199 ferric iron binding | IEA GO_REF:0000002 | ACCEPT | Summary: Ferric iron binding - transferrin binds Fe(3+). Reason: Core molecular function. Supporting Evidence: file:human/TF/TF-uniprot.txt bind two Fe(3+) ions |
| GO:0009925 basal plasma membrane | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Basal plasma membrane (polarized trophoblast). Reason: Receptor-bound transferrin at a polarized surface; non-core. Supporting Evidence: PMID:15880641 trophoblast cells |
| GO:0009986 cell surface | IDA PMID:16195351 Rab15 effector protein: a novel protein for receptor recycli... | KEEP AS NON CORE | Summary: Cell surface - receptor-bound transferrin. Reason: Surface pool of the soluble ligand; non-core. Supporting Evidence: PMID:16195351 recycling |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917807 | KEEP AS NON CORE | Summary: Endosome membrane (Reactome transferrin cycle). Reason: Receptor-bound pool at the endosomal membrane; non-core. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917814 | KEEP AS NON CORE | Summary: Endosome membrane (Reactome transferrin cycle). Reason: Receptor-bound pool at the endosomal membrane; non-core. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917835 | KEEP AS NON CORE | Summary: Endosome membrane (Reactome transferrin cycle). Reason: Receptor-bound pool at the endosomal membrane; non-core. |
| GO:0016020 membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Membrane (ortholog transfer). Reason: Transferrin is a secreted protein, not membrane-anchored; its membrane association is only via its receptor. A bare membrane location overstates this. Supporting Evidence: file:human/TF/TF-uniprot.txt SUBCELLULAR LOCATION: Secreted |
| GO:0016324 apical plasma membrane | IDA PMID:11208127 Truncated brush border myosin I affects membrane traffic in ... | KEEP AS NON CORE | Summary: Apical plasma membrane (polarized epithelial cells). Reason: Receptor-bound transferrin at a polarized surface; non-core. Supporting Evidence: PMID:11208127 polarized epithelial cells |
| GO:0019731 antibacterial humoral response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Antibacterial humoral response, inherited across the transferrin/lactoferrin family. Reason: By sequestering iron, transferrin limits bacterial growth (nutritional immunity); a secondary role. |
| GO:0019899 enzyme binding | IPI PMID:37277838 Apo- and holo-transferrin differentially interact with hepha... | KEEP AS NON CORE | Summary: Enzyme binding - transferrin binds the ferroxidase hephaestin (HEPH). Reason: A specific interaction in the cellular iron-release complex; peripheral to the core transport role. Supporting Evidence: PMID:37277838 hephaestin |
| GO:0030139 endocytic vesicle | IDA PMID:15229288 Over-expression of Rififylin, a new RING finger and FYVE-lik... | KEEP AS NON CORE | Summary: Endocytic vesicle (transferrin cycle). Reason: Receptor-bound transferrin pool during endocytosis; non-core. |
| GO:0030139 endocytic vesicle | IDA PMID:15292400 Alfy, a novel FYVE-domain-containing protein associated with... | KEEP AS NON CORE | Summary: Endocytic vesicle (transferrin cycle). Reason: Receptor-bound transferrin pool during endocytosis; non-core. |
| GO:0030139 endocytic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endocytic vesicle (transferrin cycle). Reason: Receptor-bound transferrin pool during endocytosis; non-core. |
| GO:0030316 osteoclast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Osteoclast differentiation (ortholog transfer from mouse Tf). Reason: A physiological role linked to iron supply; non-core and not shown for human. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: Clathrin-coated endocytic vesicle membrane (Reactome transferrin cycle). Reason: Receptor-bound transferrin is internalized via clathrin-coated vesicles; a cycle location for the soluble ligand, non-core. Supporting Evidence: Reactome:R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission |
| GO:0031410 cytoplasmic vesicle | IDA PMID:12857860 Myo6 facilitates the translocation of endocytic vesicles fro... | KEEP AS NON CORE | Summary: Cytoplasmic vesicle (transferrin cycle endocytic vesicles). Reason: Receptor-bound transferrin in endocytic vesicles; non-core. Supporting Evidence: PMID:12857860 endocytic vesicles |
| GO:0031647 regulation of protein stability | TAS PMID:25635054 CD81 promotes both the degradation of transferrin receptor 2... | KEEP AS NON CORE | Summary: Regulation of protein stability - holo-transferrin stabilizes TfR2. Reason: Holo-transferrin binding maintains TfR2 levels; a downstream regulatory effect. Supporting Evidence: PMID:25635054 Tfr2-mediated maintenance of hepcidin expression |
| GO:0031982 vesicle | IDA PMID:18353773 A novel sorting nexin modulates endocytic trafficking and al... | TOO GENERAL | Summary: Vesicle. Reason: Uninformative; the specific endocytic-vesicle and endosome locations are asserted elsewhere in this review. Supporting Evidence: PMID:18353773 endocytic |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IDA PMID:37277838 Apo- and holo-transferrin differentially interact with hepha... | KEEP AS NON CORE | Summary: Positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Reason: Apo/holo-transferrin influence ferroportin turnover in the iron-release mechanism; a downstream effect. Supporting Evidence: PMID:37277838 cellular iron release regulation |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-482770 | KEEP AS NON CORE | Summary: Secretory granule lumen (platelet granules). Reason: Transferrin is a cargo of platelet secretory granules; a storage/secretion location. Supporting Evidence: Reactome:R-HSA-482770 Release of platelet secretory granule components |
| GO:0034986 iron chaperone activity | IDA PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: Iron chaperone activity. Reason: Transferrin carries and hands off iron; a chaperone-like activity. Supported by a single abstract-only study, so retained as non-core rather than core. Supporting Evidence: PMID:18353247 transferrin-bound iron |
| GO:0044325 transmembrane transporter binding | IPI PMID:37277838 Apo- and holo-transferrin differentially interact with hepha... | KEEP AS NON CORE | Summary: Transmembrane transporter binding - transferrin binds ferroportin (SLC40A1). Reason: A specific interaction in the cellular iron-release complex; peripheral to the core transport role. Supporting Evidence: PMID:37277838 ferroportin |
| GO:0045178 basal part of cell | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Basal part of cell (polarized trophoblast). Reason: Receptor-bound transferrin at the basal surface; non-core. Supporting Evidence: PMID:15880641 trophoblast cells |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IDA PMID:12704209 Co-localization of the mammalian hemochromatosis gene produc... | KEEP AS NON CORE | Summary: Positive regulation of receptor-mediated endocytosis. Reason: Holo-transferrin binding drives receptor-mediated endocytosis; a downstream regulatory effect. |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: Positive regulation of receptor-mediated endocytosis. Reason: Holo-transferrin binding drives receptor-mediated endocytosis; a downstream regulatory effect. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (recycling compartment). Reason: Transferrin accumulates in the perinuclear recycling compartment during the cycle; non-core. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:20202662 Ebola virus uses clathrin-mediated endocytosis as an entry p... | KEEP AS NON CORE | Summary: Perinuclear region of cytoplasm (part_of). Reason: Transferrin accumulates in the perinuclear recycling compartment; non-core. Supporting Evidence: PMID:20202662 clathrin-mediated endocytosis |
| GO:0055037 recycling endosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Recycling endosome (transferrin cycle). Reason: Apo-transferrin recycles through recycling endosomes; non-core. |
| GO:0055037 recycling endosome | IDA PMID:15880641 Transferrin receptor co-localizes and interacts with the hem... | KEEP AS NON CORE | Summary: Recycling endosome (transferrin cycle). Reason: Apo-transferrin recycles through recycling endosomes; non-core. |
| GO:0055037 recycling endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Recycling endosome (transferrin cycle). Reason: Apo-transferrin recycles through recycling endosomes; non-core. |
| GO:0060586 multicellular organismal-level iron ion homeostasis | IMP PMID:11113131 Hepcidin, a urinary antimicrobial peptide synthesized in the... | KEEP AS NON CORE | Summary: Multicellular organismal-level iron ion homeostasis. Reason: Transferrin is central to systemic iron handling; a whole-organism physiological role, retained as non-core relative to the molecular transport function. Supporting Evidence: PMID:11113131 Hepcidin |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome (proteomics detection). Reason: Abundant plasma protein detected in exosome preparations; a secondary location. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Extracellular exosome (proteomics detection). Reason: Abundant plasma protein detected in exosome preparations; a secondary location. |
| GO:0071281 cellular response to iron ion | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: Cellular response to iron ion (genetic interaction). Reason: Downstream cellular response to iron delivery; non-core. Supporting Evidence: PMID:18353247 cellular uptake of transferrin-bound iron |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | KEEP AS NON CORE | Summary: Blood microparticle (proteomics detection). Reason: Abundant plasma protein detected in microvesicle preparations; a secondary location. Supporting Evidence: PMID:22516433 microvesicles |
| GO:1990459 transferrin receptor binding | IPI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990459 transferrin receptor binding | IPI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990459 transferrin receptor binding | IPI PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990459 transferrin receptor binding | IPI PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990459 transferrin receptor binding | IPI PMID:9546397 Crystal structure of the hemochromatosis protein HFE and cha... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990459 transferrin receptor binding | TAS PMID:9465039 The hemochromatosis gene product complexes with the transfer... | ACCEPT | Summary: Transferrin receptor binding - holo-transferrin binds TfR1/TfR2. Reason: Core molecular function enabling receptor-mediated iron delivery. Supporting Evidence: PMID:29388418 Transferrin Receptors TfR1 and TfR2 Bind Transferrin through Differing Mechanisms |
| GO:1990712 HFE-transferrin receptor complex | IDA PMID:9546397 Crystal structure of the hemochromatosis protein HFE and cha... | ACCEPT | Summary: HFE-transferrin receptor complex (part_of). Reason: Transferrin forms a complex with HFE and the transferrin receptor regulating iron uptake; a defined functional complex. Supporting Evidence: PMID:9546397 interaction with transferrin receptor |
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Download this section (compressed HTML)Q: Does human transferrin bind ferrous iron under any physiological condition, or is the ferrous-binding annotation an artifact of the assay system?
Experiment: Quantify apo/holo-transferrin binding to ferroportin and hephaestin and its effect on cellular iron efflux using purified components and cell-based efflux assays.
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