Transferrin receptor protein 1/2, PA domain (IPR037324)
Short name: TfR1/2_PA
Overlapping homologous superfamilies
- PA domain (IPR003137)
- Transferrin receptor protein 1/2, PA domain (IPR037324)
This entry represents the PA domain found in transferrin receptor proteins 1 (TfR1) and 2 (TfR2). The function of the PA domain is not clear.
The transferrin receptor 1 (TfR) is a transmembrane protein that assists iron uptake into vertebrate cells through a cycle of endo- and exocytosis of the iron transport protein transferrin (Tf). TfR binds iron-loaded (diferric) Tf at the cell surface and carries it to the endosome, where the iron dissociates from Tf. The apo-Tf remains bound to TfR until it reaches the cell surface, where apo-Tf is replaced by diferric Tf from the serum to begin the cycle again. The crystal structure of a TfR monomer reveals a 3-domain structure: a protease-like domain that closely resembles carboxy- and amino-peptidases; an apical domain consisting of a beta-sandwich; and a helical dimerisation domain. The dimerisation domain consists of a 4-helical bundle that makes contact with each of the three domains in the dimer partner [PMID: 10531064].
In humans, TfR is a homodimeric type II transmembrane protein highly expressed on brain endothelial cells. It may undergo transcytosis at the blood-brain barrier (BBB) to allow entry of iron-bound Transferrin by constitutive endocytosis [PMID: 24470444]. The TfR-facilitated transcytosis has been explored to deliver therapeutics into the brain in a noninvasive manner [PMID: 17619996, PMID: 21613623].
- cd02128 (PA_TfR)