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TFRC

GeneName

TFRC

Summary

TFRC, also known as TfR1, CD71, or TfR, is an 85 kDa transmembrane glycoprotein primarily expressed on the surface of various cell types, including erythroid progenitor cells, and plays a pivotal role in iron homeostasis. It is localised to the basolateral plasma membrane and is involved in the endocytosis of transferrin, the main iron transport protein in the bloodstream. TFRC is also implicated in various cellular processes, including receptor internalization and the regulation of iron ion transport, and has been identified as a receptor for certain viruses. Its presence in extracellular vesicles highlights its potential role in intercellular communication.

Importance

TFRC is relevant to: - Iron metabolism and related disorders, such as anaemia and hemochromatosis, through its role in iron uptake and homeostasis. - Cancer research, as it is often overexpressed in tumour cells, facilitating increased iron acquisition for rapid cell proliferation. - Neurobiology, given its involvement in iron transport across the blood-brain barrier, which is critical for neuronal function and development. - Immune responses, as it influences B cell and T cell proliferation, impacting adaptive immunity.

Top Products

For researchers investigating TFRC, we recommend two excellent primary antibodies that cater to various experimental needs. The first is the well-cited polyclonal antibody, Anti-Transferrin Receptor antibody (ab84036), which has garnered 244 citations, reflecting its reliability in Western blotting (WB). Additionally, we offer the recombinant antibody, Anti-Transferrin Receptor antibody [EPR20584] (ab214039), which is validated for multiple applications, including WB, immunohistochemistry (IHC), immunocytochemistry (ICC), and immunoprecipitation (IP). With 119 citations, this recombinant product ensures batch-to-batch consistency, making it an excellent choice for researchers seeking dependable results in their studies of the transferrin receptor. The Human Transferrin Receptor ELISA Kit (CD71) (ab272469) is a reliable option for researchers looking to measure TFRC levels in their samples.

Abcam Product Citation Summary

The data indicates that TFRC is being studied in various contexts related to ferroptosis, iron overload, and cell proliferation across different species, including humans and rats. The use of Western blotting and immunocytochemistry highlights the importance of TFRC in understanding cellular responses to iron and its implications in diseases such as cancer and conditions involving iron dysregulation.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab214039
Human
WB
Kidney proximal tubular cells
30993878
ab214039
Human
WB
Human samples
30993878
ab269513
Rat
WB
Heart tissues
35273493
ab84036
Mouse
WB
Hippocampal tissues
32205843
ab84036
Human
WB
Human cells
27384479
ab84036
Chinese hamster
ICC
Serotonin treatment effects
31723224
ab84036
Human
IHC
Triple-negative breast cancer cells
28790402
ab84036
Human
WB
RPE cells
28851903
ab84036
Human
WB
Red cell membranes
32411010
ab84036
Human
WB
SH-SY5Y cells
35624674

Function

Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity).

(Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.

(Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells.

(Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells.

(Microbial infection) Acts as a receptor for Plasmodium vivax.

Involvement in disease

Immunodeficiency 46

IMD46

An autosomal recessive primary immunodeficiency disorder characterized by early-onset chronic diarrhea, recurrent infections, hypo- or agammaglobulinemia, normal lymphocyte counts, intermittent neutropenia, and intermittent thrombocytopenia.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of the JNK pathway and promotes mitochondrial fragmentation (PubMed:26214738). Stearoylation does not affect iron uptake (PubMed:26214738).

N- and O-glycosylated, phosphorylated and palmitoylated. The serum form is only glycosylated.

Proteolytically cleaved on Arg-100 to produce the soluble serum form (sTfR).

Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the major site of palmitoylation.

Sequence Similarities

Belongs to the peptidase M28 family. M28B subfamily.

Cellular localization

Alternative names

CD71, Transferrin receptor protein 1, TR, TfR, TfR1, Trfr, T9, Transferrin receptor 1, p90, TFRC

swissprot:P02786 entrezGene:7037 omim:190010