Transferrin

Transferrins are iron-binding is_associated_with::blood plasma is_associated_with::glycoproteins that control the level of free is_associated_with::iron in is_associated_with::biological fluids. Human transferrin is encoded by the TF is_associated_with::gene.

Transferrin is_associated_with::glycoproteins bind iron tightly, but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of total body iron, it forms the most vital iron pool with the highest rate of turnover (25 mg/24 h). Transferrin has a molecular weight of around 80 KDa and contains two specific high-affinity is_associated_with::Fe(III) binding sites. The affinity of transferrin for Fe(III) is extremely high (1023 M−1 at pH 7.4) but decreases progressively with decreasing is_associated_with::pH below neutrality.

When not bound to iron, transferrin is known as "apotransferrin" (see also apoprotein).

Transport mechanism
When a transferrin protein loaded with iron encounters a is_associated_with::transferrin receptor on the surface of a cell (e.g., to erythroid precursors in the bone marrow), it binds to it and, as a consequence, is transported into the cell in a vesicle by is_associated_with::receptor-mediated endocytosis. The pH of the vesicle is reduced by hydrogen ion pumps ( ATPases) to about 5.5, causing transferrin to release its iron ions. The receptor (with its is_associated_with::ligand, transferrin, bound) is then transported through the is_associated_with::endocytic cycle back to the cell surface, ready for another round of iron uptake. Each transferrin molecule has the ability to carry two iron ions in the is_associated_with::ferric form.

The is_associated_with::gene coding for transferrin in humans is located in is_associated_with::chromosome band 3q21.

Medical professionals may check serum transferrin level in iron deficiency and in is_associated_with::iron overload disorders such as is_associated_with::hemochromatosis.

Structure
In humans, transferrin consists of a polypeptide chain containing 679 is_associated_with::amino acids. The protein is composed of alpha helices and is_associated_with::beta sheets that form two domains. The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.

The is_associated_with::amino acids which bind the iron ion to the transferrin are identical for both lobes; two is_associated_with::tyrosines, one is_associated_with::histidine, and one is_associated_with::aspartic acid. For the iron ion to bind, an is_associated_with::anion is required, preferably is_associated_with::carbonate.

Transferrin also has a transferrin iron-bound receptor; it is a disulfide-linked is_associated_with::homodimer. In humans, each monomer consists of 760 amino acids. It enables is_associated_with::ligand bonding to the transferrin, as each is_associated_with::monomer can bind to one or two molecules of iron. Each monomer consists of three domains: the protease, the helical, and the apical domains. The shape of a transferrin receptor resembles a butterfly based on the intersection of three clearly-shaped domains.

Tissue distribution
The is_associated_with::liver is the main site of transferrin synthesis but other tissues and organs, including the brain, also produce transferrin. The main role of transferrin is to deliver iron from absorption centers in the is_associated_with::duodenum and white blood cell is_associated_with::macrophages to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur. The receptor helps maintain iron is_associated_with::homeostasis in the cells by controlling iron concentrations.

Immune system
Transferrin also associated with the innate immune system. It is found in the is_associated_with::mucosa and binds iron, thus creating an environment low in free iron that impedes bacterial survival in a process called iron withholding. The level of transferrin decreases in inflammation.

Role in disease
An increased plasma transferrin level is often seen in patients suffering from iron deficiency is_associated_with::anemia. A decreased plasma transferrin can occur in iron overload diseases and protein malnutrition. An absence of transferrin results from a rare genetic disorder known as is_associated_with::atransferrinemia, a condition characterized by anemia and is_associated_with::hemosiderosis in the heart and liver that leads to heart failure and many other complications.

Most recently, transferrin and its receptor have been shown to diminish is_associated_with::tumour cells when the receptor is used to attract is_associated_with::antibodies.

Other effects
The metal-binding properties of transferrin have a great influence on the biochemistry of is_associated_with::plutonium in humans.

is_associated_with::Carbohydrate deficient transferrin increases in the blood with heavy is_associated_with::ethanol consumption and can be monitored through laboratory testing.

Pathology
is_associated_with::Atransferrinemia is associated with a deficiency in transferrin.

In nephrotic syndrome, urinary loss of transferrin, along with other serum proteins such as thyroxine-binding globulin, gammaglobulin, and anti-thrombin III, can manifest as iron-resistant microcytic anemia.

Reference ranges
An example reference range for transferrin is 204–360 mg/dL. Laboratory test results should always be interpreted using the reference range provided by the laboratory that performed the test.



A high transferrin level may indicate an is_associated_with::iron deficiency anemia. Levels of is_associated_with::serum iron and is_associated_with::total iron binding capacity (TIBC) are used in conjunction with transferrin to specify any abnormality. See interpretation of TIBC.

Interactions
Transferrin has been shown to interact with is_associated_with::insulin-like growth factor 2 and is_associated_with::IGFBP3. Transcriptional regulation of transferrin is upregulated by retinoic acid.

Related proteins
Members of the family include blood serotransferrin (or siderophilin, usually simply called transferrin); is_associated_with::lactotransferrin (lactoferrin); milk transferrin; egg white is_associated_with::ovotransferrin (conalbumin); and membrane-associated is_associated_with::melanotransferrin.