| Gene | TFRC |
| UniProt | [P02786](https://www.uniprot.org/uniprot/P02786) |
| Molecular Weight | 84-90 kDa (monomer), 180 kDa (dimer) |
| Subcellular Localization | Plasma membrane, Endosomes |
| PDB Structures | [1SUV](https://www.rcsb.org/structure/1SUV), [1DE4](https://www.rcsb.org/structure/1DE4) |
| Aliases | TfR, TfR1, CD71, p90 |
Transferrin Receptor 1 (TFRC, also known as TfR, TfR1, or CD71) is a transmembrane glycoprotein that mediates cellular iron uptake by binding and internalizing iron-loaded transferrin. As the primary gateway for iron entry into most cells, TFRC plays a critical role in regulating iron homeostasis and is increasingly recognized for its involvement in neurodegenerative diseases characterized by iron dysregulation.[1]
TFRC is a type II transmembrane protein that functions as a homodimer:[2]
Domain organization:
The extracellular domain contains three subdomains:
TFRC is the primary mechanism for cellular iron acquisition:[3]
Iron uptake pathway:
Iron homeostasis regulation:
Cell proliferation:
TFRC-mediated iron uptake is implicated in several neurodegenerative diseases:[4]
Parkinson's Disease:
Alzheimer's Disease:
Neurodegeneration with Brain Iron Accumulation (NBIA):
Iron-Induced Toxicity:
TFRC ↑ → Iron uptake ↑ → Fenton chemistry → ROS ↑ → Lipid peroxidation → Cell death
α-Synuclein Interaction:
Transferrin Dysregulation:
Targeting TFRC-mediated iron uptake for neuroprotection:[7]
| Strategy | Mechanism | Status |
|---|---|---|
| Deferiprone | Chelates labile iron, crosses BBB | Phase II/III trials (PD) |
| Deferoxamine | Iron chelation, limited BBB penetration | Preclinical |
| Deferasirox | Oral chelator | Preclinical |
| Ferritin-based chelators | Targeted delivery | Research |
| Interacting Partner | Function | Relevance |
|---|---|---|
| Transferrin | Iron transport protein | Primary ligand |
| DMT1 | Endosomal iron exporter | Sequential transport |
| HFE | Iron regulation | Competitive binding |
| IRP1/IRP2 | Post-transcriptional regulation | mRNA stability |
| Clathrin | Endocytosis | Receptor internalization |
Kawabata et al., Molecular cloning of transferrin receptor 2 (2013) — Characterization of TFRC structure and function.
Mochizuki et al., Iron and the transferrin receptor in Parkinson's disease (2021) — Demonstrates TFRC upregulation in PD substantia nigra.
Xie et al., Transferrin receptor is a specific ferroptosis marker (2016) — Cancer Research. Establishes TFRC as a ferroptosis marker.
Rouault, Iron metabolism in the central nervous system (2013) — Physiological Reviews. Comprehensive review of brain iron homeostasis.
Billings et al., Iron accumulation and lipid peroxidation in Alzheimer's disease (2023) — Links TFRC-mediated iron uptake to AD pathology.
Gomme PT, et al. [Transferrin: structure, function and potential therapeutic applications](https://doi.org/10.1016/S1359-6446(04). Drug Discovery Today. 2005. ↩︎
Cheng Y, et al. [Structure of the human transferrin receptor-transferrin complex](https://doi.org/10.1016/S0092-8674(04). Cell. 2004. ↩︎
Richardson DR, Ponka P. [The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells](https://doi.org/10.1016/S0304-4157(96). Biochimica et Biophysica Acta. 1997. ↩︎
Mochizuki H, et al. Iron and the transferrin receptor in Parkinson's disease. Movement Disorders. 2021. ↩︎ ↩︎
Ayton S, et al. Brain iron is associated with accelerated cognitive decline in people with Alzheimer pathology. Molecular Psychiatry. 2020. ↩︎
Davies KM, et al. Localization of iron and transferrin receptor in Parkinson's disease brain. Neurobiology of Disease. 2021. ↩︎
Devos D, et al. Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxidants & Redox Signaling. 2014. ↩︎