Transferrin receptor (TfR) is a
carrier protein
A membrane transport protein (or simply transporter) is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane ...
for
transferrin
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 encode ...
. It is needed for the import of
iron
Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
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.
Figure 3: The cycle of transferrin and transferrin receptor 1-mediated cellular iron uptake.
/ref> The existence of a receptor for transferrin iron uptake had been recognized over half a century back. Earlier two transferrin receptors in humans, transferrin receptor 1
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. TfR1 is required for iron import from transferrin into cells by endocytosis.
Structure and fun ...
and transferrin receptor 2
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.
F ...
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 (GAPDH, EC 1.2.1.12) 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.
Post-transcriptional regulation
Low iron concentrations promote increased levels of transferrin receptor, to increase iron intake into the cell. Thus, transferrin receptor maintains cellular iron homeostasis
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically imp ...
.
TfR production in the cell is regulated according to iron levels by iron-responsive element-binding protein
The iron-responsive element-binding proteins, also known as IRE-BP, IRBP, IRP and IFR
, bind to iron-responsive elements (IREs) in the regulation of human iron metabolism.
Function
ACO1, or IRP1, is a bifunctional protein that functions as an ...
s, IRP1 and IRP2. In the absence of iron, one of these proteins (generally IRP2) binds to the hairpin like structure (IRE
Ire or IRE may refer to:
Ire
* Extreme anger; intense fury
* Irē, the Livonian name for Mazirbe, Latvia
* A town in Oye, Nigeria
* ''Ire'' (album), a 2015 album by the Australian metalcore band Parkway Drive
* Ire (Iliad), a town mentioned in ...
) that is in the 3' UTR of the TfR mRNA. Once binding occurs, the mRNA is stabilized and degradation is inhibited.
See also
* Transferrin receptor 1
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. TfR1 is required for iron import from transferrin into cells by endocytosis.
Structure and fun ...
* Transferrin receptor 2
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.
F ...
* Soluble transferrin receptor
* GAPDH
Glyceraldehyde 3-phosphate dehydrogenase (abbreviated GAPDH) () is an enzyme of about 37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molecules. In addition to this long establishe ...
References
Further reading
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Figure 3: Cellular uptake of iron through the Tf system via receptor-mediated endocytosis.
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External links
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{{Iron metabolism
Iron metabolism
Transferrins