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]
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 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]
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.
CD23, also known as Fc epsilon RII, or FcεRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 is a C-type lectin. It is found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets.
Human homeostatic iron regulator protein, also known as the HFE protein, is a protein which in humans is encoded by the HFE gene. The HFE gene is located on short arm of chromosome 6 at location 6p22.2
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium.
Transcytosis is a type of transcellular transport in which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side. Examples of macromolecules transported include IgA, transferrin, and insulin. While transcytosis is most commonly observed in epithelial cells, the process is also present elsewhere. Blood capillaries are a well-known site for transcytosis, though it occurs in other cells, including neurons, osteoclasts and M cells of the intestine.
Vascular cell adhesion protein 1 also known as vascular cell adhesion molecule 1 (VCAM-1) or cluster of differentiation 106 (CD106) is a protein that in humans is encoded by the VCAM1 gene. VCAM-1 functions as a cell adhesion molecule.
B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity.
Transferrin receptor (TfR) is a carrier protein for transferrin. It is needed for the import of iron into the cell and is regulated in response to intracellular iron concentration. It imports iron by internalizing the transferrin-iron complex through receptor-mediated endocytosis. The existence of a receptor for transferrin iron uptake has been recognized since the late 1950s. Earlier two transferrin receptors in humans, transferrin receptor 1 and transferrin receptor 2 had been characterized and until recently cellular iron uptake was believed to occur chiefly via these two well documented transferrin receptors. Both these receptors are transmembrane glycoproteins. TfR1 is a high affinity ubiquitously expressed receptor while expression of TfR2 is restricted to certain cell types and is unaffected by intracellular iron concentrations. TfR2 binds to transferrin with a 25-30 fold lower affinity than TfR1. Although TfR1 mediated iron uptake is the major pathway for iron acquisition by most cells and especially developing erythrocytes, several studies have indicated that the uptake mechanism varies depending upon the cell type. It is also reported that Tf uptake exists independent of these TfRs although the mechanisms are not well characterized. The multifunctional glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase has been shown to utilize post translational modifications to exhibit higher order moonlighting behavior wherein it switches its function as a holo or apo transferrin receptor leading to either iron delivery or iron export respectively.
Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene. LRP1 is also a key signalling protein and, thus, involved in various biological processes, such as lipoprotein metabolism and cell motility, and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer.
Transferrin receptor 2 (TfR2) is a protein that in humans is encoded by the TFR2 gene. This protein is involved in the uptake of transferrin-bound iron into cells by endocytosis, although its role is minor compared to transferrin receptor 1.
Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.
Melanotransferrin is a protein that in humans is encoded by the MFI2 gene. MFI2 has also recently been designated CD228.
4F2 cell-surface antigen heavy chain is a protein that in humans is encoded by the SLC3A2 gene.
CD47 also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a don't eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis.
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
Fc receptor-like protein 5 is a protein that in humans is encoded by the FCRL5 gene. FCRL5 has also been designated as CD307.
Low affinity immunoglobulin gamma Fc region receptor III-A is a protein that in humans is encoded by the FCGR3A gene. It is also known as CD16a as it is part of the cluster of differentiation cell surface molecules.
CD160 antigen is a protein that in humans is encoded by the CD160 gene.
Haemochromatosis type 3 is a type of iron overload disorder associated with deficiencies in transferrin receptor 2. It exhibits an autosomal recessive inheritance pattern. The first confirmed case was diagnosed in 1865 by French doctor Trousseau. Later in 1889, the German doctor von Recklinghausen indicated that the liver contains iron, and due to bleeding being considered to be the cause, he called the pigment "Haemochromatosis." In 1935, English doctor Sheldon's groundbreaking book titled, Haemochromatosis, reviewed 311 patient case reports and presented the idea that haemochromatosis was a congenital metabolic disorder. Hereditary haemochromatosis is a congenital disorder which affects the regulation of iron metabolism thus causing increased gut absorption of iron and a gradual build-up of pathologic iron deposits in the liver and other internal organs, joint capsules and the skin. The iron overload could potentially cause serious disease from the age of 40–50 years. In the final stages of the disease, the major symptoms include liver cirrhosis, diabetes and bronze-colored skin. There are four types of hereditary hemochromatosis which are classified depending on the age of onset and other factors such as genetic cause and mode of inheritance.
CD96 or Tactile is a protein that in humans is encoded by the CD96 gene. CD96 is a receptor protein which is expressed on T cells and NK cells and shares sequence similarity with CD226. The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesion of activated T and NK cells to their target cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. CD96 is a transmembrane glycoprotein that has three extracellular immunoglobulin-like domains and is expressed by all resting human and mouse NK cells. CD96 main ligand is CD155. CD 96 has approximately 20% homology with CD226 and competed for binding to CD155 with CD226.
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