Antibodies to Transferrin and ELISA kits
 

Antibodies to Transferrin receptors (TfR1, and TfR2)
 

M= Mouse; R=Rat; H=Human; Rb=Rabbit; G=goat; S=Sheep; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein
Rb=rabbit; m=mouse; r=rat; h=human; s=sheep; b=bovine; ch=chicken; d=dog; ~CT or ~NT=near C or N-terminus. EC=Extracellular; CL=Cytoplasmic loop.

 

Ferritin, Transferrin, and Transferrin Receptor (TfR1 and TfR2) Antibodies-General Information

Elemental iron is required for a variety of normal cellular functions and vital for proper growth and development. However, natural iron is quite insoluble and excess iron is harmful, since it can catalyze the formation of potentially damaging reactive oxygen species. Humans also have very limited capacity to excrete iron. Therefore, cells have developed mechanisms to improve solubility of iron and to control intracellular iron levels at the point of absorption in the intestine and other tissue. The major pool of body iron (~85%; 40-50 mg/kg) is found in circulating hemoglobin and muscle myoglobin. Iron absorption occurs primarily in the intestine (duodenum) and inversely related to body iron reserve. Several proteins including Ferritin, transferrin (Tf), transferrin receptors (TfRs), and iron regulatory proteins (IRPs) etc play a key role in iron metabolism.

Transferrin (Tf), a serum glycoprotein of ~80 kDa and synthesized in the liver, is the primary protein of inter-organ transport of nonheme iron. Tf can bind two iron atoms. Normally about 30% Tf is iron-saturated to prevent accumulation of toxic iron. 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 (95 kDa 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 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. TfR2-alpha can also bind transferrin and play a role in iron transport.

Ferritin is the major protein involved in iron sequestration and detoxification. Ferritin is found in all living species and its three dimensional structure is conserved in all species despite very low sequence identity from bacteria to human. Mammalian liver and spleen ferritin (~450 kDa) consists of 24 subunits of 2 species, the heavy subunit (~21 kDa; FTH) and the light subunit (~ 19 kDa; FTL). The 2 types of apoferritin subunits were designated H and L for heart and liver, respectively. Ferritin molecules from plants and bacteria contain only H-type chains, where 'H-type' is associated with the presence of centers catalyzing the oxidation of two Fe(II) atoms. FTL subunit (rich in human liver and spleen) is coded by a gene in segment 19q13.3 and FTH subunit (rich in human heart) is located on chromosome 11. Ferritin is capable of storing up to 4,500 atoms of ferric iron. The H-to-L ratio within ferritin varies in a tissue-specific manner and is also influenced by pathophysiological conditions, including inflammation and malignancy. Hyperferritinemia-cataract syndrome has a mutation in the iron response element (IRE) in the 5-prime noncoding region of the FTL gene. Synthesis of both ferritin subunits is controlled by a common cytosolic protein, iron regulatory proteins (IRPs), which binds to the iron-responsive element (IRE) in the 5'-UTR of the H- and L-ferritin mRNAs. H-chains are important for Fe(II) oxidation and L-chains assist in core formation.