Transferrin receptor

Function

Transferrin receptor (TfR) imports iron into the cell by receptor-mediated endocytosis of transferrin-iron complex. TfR is regulated by intracellular iron concentration. The amount of TfR expressed on the cell is proportional to the cell’s need for iron. The TfR has selective affinity for diferric-transferrin. The TfR-transferrin complex is internalized by the cell and iron is released to the cytosol. The TfR-apotransferrin complex returns to the extracellular surface where the apotransferrin dissociates and is replaced by diferric-transferrin^[1].

Relevance

TfR is a potential determinant of iron loading in congenital anemias^[2].

Structural highlights

(1suv).

Human transferrin receptor ectodomain dimer (grey and green) complex with transferrin N-lobe (pink and yellow) and C-lobe (cyan and magenta) and carbonate, 1suv

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3D structures of transferrin receptor3D structures of transferrin receptor

Updated on 22-January-2024

Domains – apical 197-378; ectodomain 121-760

1cx8 – hTfR ectodomain – human
6y76, 8p0z - hTfR apical domain
1de4 - hTfR ectodomain + hemochromatosis protein + β-2-microglobulin
1suv, 6soy, 6soz - hTfR ectodomain + transferrin
6okd - hTfR ectodomain + TfR-binding cysteine-dense peptide
6d03, 6d04, 6d05 - hTfR ectodomain + transferrin – Cryo EM
6gsr, 6h5i - hTfR ectodomain + ferritin heavy chain – Cryo EM
6s9j - hTfR ectodomain + PRE-GP-C
3s9l, 3s9m, 3s9n - hTfR ectodomain + transferrin N-lobe
2nsu - hTfR ectodomain in dog retrovirus – Cryo EM
3kas - hTfR ectodomain + Machupo virus GP1
6wrv, 6wrw, 6wrx - hTfR ectodomain + synthetic protein
7zqs - hTfR + DNA – Cryo EM

ReferencesReferences

↑ Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999 Apr;21(4):396-9. PMID:10192390 doi:http://dx.doi.org/10.1038/7727
↑ Cazzola M, Beguin Y, Bergamaschi G, Guarnone R, Cerani P, Barella S, Cao A, Galanello R. Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis. Br J Haematol. 1999 Sep;106(3):752-5. PMID:10468869

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999 Apr;21(4):396-9. PMID:10192390 doi:http://dx.doi.org/10.1038/7727

[2] Cazzola M, Beguin Y, Bergamaschi G, Guarnone R, Cerani P, Barella S, Cao A, Galanello R. Soluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis. Br J Haematol. 1999 Sep;106(3):752-5. PMID:10468869

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