transferrin

Transferrin
PDB rendering based on 1a8e.
Available structures
1a8e, 1a8f, 1b3e, 1bp5, 1btj, 1d3k, 1d4n, 1dtg, 1fqe, 1fqf, 1jqf, 1n7w, 1n7x, 1n84, 1oqg, 1oqh, 1ryo, 1suv, 2hau, 2hav, 2o7u, 2o84
Identifiers
Symbols	TF; DKFZp781D0156; PRO1557; PRO2086
External IDs	OMIM: 190000 MGI: 98821 HomoloGene: 68153
Gene ontology Molecular function • ferric iron binding • metal ion binding Cellular component • extracellular region • endosome • endocytic vesicle Biological process • ion transport • iron ion transport • cellular iron ion homeostasis
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7018	22041
Ensembl	ENSG00000091513	ENSMUSG00000032554
UniProt	P02787	Q3UBW7
RefSeq	NM_001063 (mRNA)	NM_133977 (mRNA)
	NP_001054 (protein)	NP_598738 (protein)
Location	Chr 3: 134.95 - 134.98 Mb	Chr 9: 103.07 - 103.09 Mb
PubMed search	[1]	[2]

Transferrin is a blood plasma protein for iron ion delivery that, in humans, is encoded by the TF gene.^[1] Transferrin is a glycoprotein that binds iron very tightly but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of the total body iron, it is the most important iron pool, with the highest rate of turnover (25 mg/24 h). Transferrin has a molecular weight of around 80 kiloDaltons and contains 2 specific high-affinity Fe(III) binding sites. The affinity of transferrin for Fe(III) is extremely high (10²³ M^-1 at pH 7.4)^{[citation needed]} but decreases progressively with decreasing pH below neutrality.

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

Transport mechanism

When a transferrin protein loaded with iron encounters a 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. The pH of the vesicle is reduced by hydrogen ion pumps (H⁺ ATPases), causing transferrin to release its iron ions. The receptor (with its ligand, transferrin, bound) is then transported through the 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 ferric form (Fe³⁺).

The gene coding for transferrin in humans is located in chromosome band 3q21.^[1] Research on king snakes by Dessauer and Zwiefel in 1981 revealed that the inheritance of transferrin is a codominant trait.

Medical professionals may check serum transferrin level in iron deficiency, hemochromatosis, and other iron overload disorders.

Structure

In humans, transferrin consists of a poly peptide chain containing 679 amino acids. It is a complex composed of alpha helices and beta sheets to form two domains (the first situated in the N-terminus and the second in the C-terminus).^[2] The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.

The amino acids which bind the iron ion to the transferrin are identical for both lobes; two tyrosines, one histidine, and one aspartic acid. In order for the iron ion to bind an anion is required, preferably carbonate (CO₃^2-).^[2]

Transferrin also has a transferrin iron-bound receptor; it is a disulfide-linked homodimer.^[3] In humans, each monomer consists of 760 amino acids. It enables ligand bonding to the transferrin, as each monomer can bind to one or two molecules of iron. Each monomer consists of three domains: the protease domain, the helical domain, and apical domain. The shape of transferrin receptor resembles a butterfly-like complex, due to the three clearly shaped domains.^[2]

Transferrin bound to its receptor.[4]

Transferrin receptor complex.[5]

Tissue distribution

The liver is the main source of manufacturing transferrin, but other sources such as the brain also produce this molecule . The main role of transferrin is to deliver iron from absorption centres in the duodenum and red blood cell macrophages to all tissues. Predominantly, transferrin plays a key role where erythropoiesis and active cell division occur.^[3] In order for iron ion to be introduced into the cell a carrier protein is used, known as a transferrin receptor. The receptor helps maintain iron homeostasis in the cells by controlling iron concentrations.^[3]

Immune system

Transferrin is also associated with the innate immune system. Transferrin is found in the mucosa and binds iron, thus creating an environment low in free iron, where few bacteria are able to survive. The levels of transferrin decreases in inflammation^[6], seeming contradictory to its function.

Transferrin imbalance can have serious health effects for those with low or high serum transferrin levels. A patient with an increased serum transferrin level often suffers from iron deficiency anemia.^[3] A patient with decreased plasma transferrin can suffer from iron overload diseases and protein malnutrition. An absence of transferrin in the body creates a rare genetic disorder known as atransferrinemia; a condition characterized by anemia and hemosiderosis in the heart and liver that leads to many complications including heart failure. Most recently, transferrin and its receptor have been tested to diminish tumour cells by using the receptor to attract antibodies. As research continues and additional information is collected possibly life saving, is being discovered through the molecular biology and protein biochemistry worlds.^[3]

Other effects

The metal binding properties of transferrin have a great influence on the biochemistry of plutonium in humans. Transferrin has a bacteriocidal effect on bacteria, in that it makes Fe³⁺ unavailable to the bacteria.

Pathology

A deficiency is associated with atransferrinemia.

Reference ranges

Normal reference ranges for transferrin are 204 - 360 mg/dL.^[7]

Reference ranges for blood tests, comparing blood content of transferrin and other iron-related compounds (shown in brown and orange) with other constituents.

A high transferrin level may indicate iron deficiency anemia. Levels of serum iron and 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 Insulin-like growth factor 2^[8] and IGFBP3.^[9]

See also

• Beta-2 transferrin
• Transferrin receptor
• Total iron-binding capacity
• Transferrin saturation

References

Further reading

v • d • e PDB Gallery 1a8e: HUMAN SERUM TRANSFERRIN, RECOMBINANT N-TERMINAL LOBE   1a8f: HUMAN SERUM TRANSFERRIN, RECOMBINANT N-TERMINAL LOBE   1b3e: HUMAN SERUM TRANSFERRIN, N-TERMINAL LOBE, EXPRESSED IN PICHIA PASTORIS   1bp5: HUMAN SERUM TRANSFERRIN, RECOMBINANT N-TERMINAL LOBE, APO FORM   1btj: HUMAN SERUM TRANSFERRIN, RECOMBINANT N-TERMINAL LOBE, APO FORM, CRYSTAL FORM 2   1d3k: HUMAN SERUM TRANSFERRIN   1d4n: HUMAN SERUM TRANSFERRIN   1dtg: HUMAN TRANSFERRIN N-LOBE MUTANT H249E   1fqe: CRYSTAL STRUCTURES OF MUTANT (K206A) THAT ABOLISH THE DILYSINE INTERACTION IN THE N-LOBE OF HUMAN TRANSFERRIN   1fqf: CRYSTAL STRUCTURES OF MUTANT (K296A) THAT ABOLISH THE DILYSINE INTERACTION IN THE N-LOBE OF HUMAN TRANSFERRIN   1jqf: Human Transferrin N-Lobe Mutant H249Q   1n7w: Crystal Structure of Human Serum Transferrin, N-Lobe L66W mutant   1n7x: HUMAN SERUM TRANSFERRIN, N-LOBE Y45E MUTANT   1n84: HUMAN SERUM TRANSFERRIN, N-LOBE   1oqg: Crystal structure of the D63E mutant of the N-lobe human transferrin   1oqh: Crystal Structure of the R124A mutant of the N-lobe human transferrin   1ryo: Human serum transferrin, N-lobe bound with oxalate   1suv: Structure of Human Transferrin Receptor-Transferrin Complex   2hau: Apo-Human Serum Transferrin (Non-Glycosylated)   2hav: Apo-Human Serum Transferrin (Glycosylated)   2o7u: Crystal structure of K206E/K296E mutant of the N-terminal half molecule of human transferrin   2o84: Crystal structure of K206E mutant of N-lobe human transferrin

External links

• MeSH Transferrin

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