Elemental iron is required for a variety of normal cellular functions and vital for proper growth and development. Transferrin (Tf), a serum glycoprotein of ~80kD and synthesized in the liver, is the primary protein of inter-organ transport of nonheme iron. Tf can bind two iron atoms. Tf binds to membrane Transferrin receptors (TfRs) and taken up by endocytosis. Iron is released from Tf, within acidic endosomes, into the cytoplasm apparently through the action of DMT1. The apoTf-TfR complex is returned to the cell surface, where, apo-Tf dissociates from TfR at the extracellular pH. The classical TfR, now termed TfR1, is a homodimeric (95kD subunits) type II membrane glycoprotein that binds two molecules of Tf. Human TfR1 (human 760 aa; mouse 763 aa) has a cytoplasmic domain 1-67aa, 68-88 aa TM, and 89-760 aa as extracellular domains. A monomeric serum form or soluble TfR1 (~80kD) also exists that lacks residues 1-100 aa. Recently, a second Tf receptor, TfR2, has been cloned and characterized. TfR2 shares 45% identity with TfR1, and 27% with PMSA. Human TfR2 (human alpha 801 aa, Chromosome 7q22; mouse alpha 798 aa;) is predicted to contain a cytoplasmic domain of 1-80 aa, 1 TM domain followed by 105-801aa as the extracellular domain. It is highly expressed in liver and peripheral blood mononuclear cells. In contrast to Tfr1, expression of Tfr2 is not down regulated as a result of iron overload, consistent with the absence iron-responsive element in TfR2. It is alternatively spliced to alpha and beta isoforms. TfR2-beta protein lacked the N-terminal portion of the TfR2-alpha including the putative TM domain.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.