Transferrin_receptor_1
Transferrin receptor 1
Protein-coding gene in the species Homo sapiens
Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene.[5][6] TfR1 is required for iron import from transferrin into cells by endocytosis.[7][8]
TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis.[9]
TfR1 as a potential new target in cases of human leukemia & lymphoma. InatherYs, in Évry, France, developed a candidate drug, INA01 antibody (anti-CD71) that showed efficacy in pre-clinical studies in the therapy of two incurable orphan oncohematological diseases: the adult T cell leukemia (ATLL) caused by HTLV-1 and the Mantle cell lymphoma (MCL).[citation needed]
TfR1 expressed on the endothelial cells of the blood-brain barrier (BBB) is used also in preclinical research to allow the delivery of large molecules including antibodies into the brain.[10] Some of the TfR1 targeting antibodies have been shown to cross the blood-brain barrier, without interfering with the uptake of iron. Amongst those are the mouse anti rat-TfR antibody OX26[11] and the rat anti mouse-TfR antibody 8D3.[12] The affinity of the antibody-TfR interaction seems to be important determining the success of transcytotic transport over endothelial cells of the BBB. Monovalent TfR interaction favors BBB transport due to altered intracellular sorting pathways. Avidity effects of bivalent interactions redirecting transport to the lysosome.[13] Also, reducing TfR binding affinity directly promote dissociation from the TfR which increase brain parenchymal exposure of the TfR binding antibody.[14]
TfR1 has been shown to interact with GABARAP[15] and HFE.[16][17]
CD71 is a robust immunohistochemistry marker for chorionic villi, especially in necrotic specimens. Among white blood cells and precursors, CD71 is expressed only by erythroid precursors within the normal hematopoietic marrow and spleen, in contrast to glycophorin that marks all types of red blood cells.[18]
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M (July 1981). "Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin". Proceedings of the National Academy of Sciences of the United States of America. 78 (7): 4515–9. Bibcode:1981PNAS...78.4515S. doi:10.1073/pnas.78.7.4515. PMC 319822. PMID 6270680.
- Aisen P (November 2004). "Transferrin receptor 1". The International Journal of Biochemistry & Cell Biology. 36 (11): 2137–43. doi:10.1016/j.biocel.2004.02.007. PMID 15313461.
- Johnsen KB, Burkhart A, Thomsen LB, Andresen TL, Moos T (October 2019). "Targeting the transferrin receptor for brain drug delivery" (PDF). Progress in Neurobiology. 181: 101665. doi:10.1016/j.pneurobio.2019.101665. PMID 31376426. S2CID 199405122.
- Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, et al. (January 2014). "Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle". Neuron. 81 (1): 49–60. doi:10.1016/j.neuron.2013.10.061. PMID 24411731.
- Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP" (PDF). FEBS Letters. 518 (1–3): 101–6. doi:10.1016/S0014-5793(02)02655-8. PMID 11997026. S2CID 29391940.
- Feder JN, Penny DM, Irrinki A, Lee VK, Lebrón JA, Watson N, et al. (February 1998). "The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1472–7. Bibcode:1998PNAS...95.1472F. doi:10.1073/pnas.95.4.1472. PMC 19050. PMID 9465039.
- West AP, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ (December 2000). "Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE". The Journal of Biological Chemistry. 275 (49): 38135–8. doi:10.1074/jbc.C000664200. PMID 11027676.
- Overview of all the structural information available in the PDB for UniProt: P02786 (Human Transferrin receptor protein 1) at the PDBe-KB.
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