Transferrins
Transferrins are produced in the liver and contain binding sites for two Fe3+ ions. Transferrins are not limited to only binding to iron but also to different metal ions.
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma.
- Crichton RR, Charloteaux-Wauters M (May 1987). “Iron transport and storage”. European Journal of Biochemistry. 164 (3): 485–506. doi:10.1111/j.1432-1033.1987.tb11155.x. PMID 3032619.
They are produced in the liver and contain binding sites for two Fe3+ ions.
- Hall DR, Hadden JM, Leonard GA, Bailey S, Neu M, Winn M, Lindley PF (January 2002). “The crystal and molecular structures of diferric porcine and rabbit serum transferrins at resolutions of 2.15 and 2.60 A, respectively”. Acta Crystallographica. Section D, Biological Crystallography. 58 (Pt 1): 70–80. doi:10.1107/s0907444901017309. PMID 11752780.
Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.
- Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, et al. (May 1984). “Human transferrin: cDNA characterization and chromosomal localization”. Proceedings of the National Academy of Sciences of the United States of America. 81 (9): 2752–6. Bibcode:1984PNAS…81.2752Y. doi:10.1073/pnas.81.9.2752. PMC 345148. PMID 6585826.
- Kawabata H (March 2019). “Transferrin and transferrin receptors update”. Free Radical Biology & Medicine. 133: 46–54. doi:10.1016/j.freeradbiomed.2018.06.037. PMID 29969719. S2CID 49674402.
Transferrin 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 Fe(III) binding sites. The affinity of transferrin for Fe(III) is extremely high (association constant is 1020 M−1 at pH 7.4) but decreases progressively with decreasing pH below neutrality. Transferrins are not limited to only binding to iron but also to different metal ions.
- Aisen P, Leibman A, Zweier J (March 1978). “Stoichiometric and site characteristics of the binding of iron to human transferrin”. The Journal of Biological Chemistry. 253 (6): 1930–7. doi:10.1016/S0021-9258(19)62337-9. PMID 204636.
- Nicotra S, Sorio D, Filippi G, De Gioia L, Paterlini V, De Palo EF, et al. (November 2017). “Terbium chelation, a specific fluorescent tagging of human transferrin. Optimization of conditions in view of its application to the HPLC analysis of carbohydrate-deficient transferrin (CDT)”. Analytical and Bioanalytical Chemistry. 409 (28): 6605–6612. doi:10.1007/s00216-017-0616-z. PMID 28971232. S2CID 13929228.
These glycoproteins are located in various bodily fluids of vertebrates. Some invertebrates have proteins that act like transferrin found in the hemolymph.
- MacGillivray RT, Moore SA, Chen J, Anderson BF, Baker H, Luo Y, et al. (June 1998). “Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release”. Biochemistry. 37 (22): 7919–28. doi:10.1021/bi980355j. PMID 9609685.
- Dewan JC, Mikami B, Hirose M, Sacchettini JC (November 1993). “Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release”. Biochemistry. 32 (45): 11963–8. doi:10.1021/bi00096a004. PMID 8218271.
- Baker EN, Lindley PF (August 1992). “New perspectives on the structure and function of transferrins”. Journal of Inorganic Biochemistry. 47 (3–4): 147–60. doi:10.1016/0162-0134(92)84061-q. PMID 1431877.
When not bound to iron, transferrin is known as “apotransferrin” (see also apoprotein).
Note: Main article: Cofactor (biochemistry) Some enzymes do not need additional components to show full activity. Others require non-protein molecules called cofactors to be bound for activity.
- de Bolster MW (1997). “Glossary of Terms Used in Bioinorganic Chemistry: Cofactor”. International Union of Pure and Applied Chemistry. Archived from the original on 21 January 2017. Retrieved 30 October 2007.
Cofactors can be either inorganic (e.g., metal ions and iron–sulfur clusters) or organic compounds (e.g., flavin and heme). These cofactors serve many purposes; for instance, metal ions can help in stabilizing nucleophilic species within the active site.
- Voet D, Voet J, Pratt C (2016). Fundamentals of Biochemistry. Hoboken, New Jersey: John Wiley & Sons, Inc. p. 336. ISBN 978-1-118-91840-1.
Organic cofactors can be either coenzymes, which are released from the enzyme’s active site during the reaction, or prosthetic groups, which are tightly bound to an enzyme. Organic prosthetic groups can be covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase).
- Chapman-Smith A, Cronan JE (September 1999). “The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity”. Trends in Biochemical Sciences. 24 (9): 359–363. doi:10.1016/s0968-0004(99)01438-3. PMID 10470036.
An example of an enzyme that contains a cofactor is carbonic anhydrase, which uses a zinc cofactor bound as part of its active site.
- Fisher Z, Hernandez Prada JA, Tu C, Duda D, Yoshioka C, An H, Govindasamy L, Silverman DN, McKenna R (February 2005). “Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II”. Biochemistry. 44 (4): 1097–115. doi:10.1021/bi0480279. PMID 15667203.
These tightly bound ions or molecules are usually found in the active site and are involved in catalysis.
- Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN0-7167-4955-6.]: 8.1.1
For example, flavin and heme cofactors are often involved in redox reactions.
- Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN0-7167-4955-6.]: 17
Enzymes that require a cofactor but do not have one bound are called apoenzymes or apoproteins. An enzyme together with the cofactor(s) required for activity is called a holoenzyme (or haloenzyme). The term holoenzyme can also be applied to enzymes that contain multiple protein subunits, such as the DNA polymerases; here the holoenzyme is the complete complex containing all the subunits needed for activity.
- Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry (5th ed.). San Francisco: W.H. Freeman. ISBN0-7167-4955-6.
Occurrence and function
Transferrins are glycoproteins that are often found in biological fluids of vertebrates. When a transferrin protein loaded with iron encounters a transferrin receptor on the surface of a cell, e.g., erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a vesicle by receptor-mediated endocytosis.
- Halbrooks PJ, He QY, Briggs SK, Everse SJ, Smith VC, MacGillivray RT, Mason AB (April 2003). “Investigation of the mechanism of iron release from the C-lobe of human serum transferrin: mutational analysis of the role of a pH sensitive triad”. Biochemistry. 42 (13): 3701–7. doi:10.1021/bi027071q. PMID 12667060.
The pH of the vesicle is reduced by hydrogen ion pumps (H+
ATPases) to about 5.5, causing transferrin to release its iron ions.
- MacGillivray RT, Moore SA, Chen J, Anderson BF, Baker H, Luo Y, et al. (June 1998). “Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release”. Biochemistry. 37 (22): 7919–28. doi:10.1021/bi980355j. PMID 9609685.
Iron release rate is dependent on several factors including pH levels, interactions between lobes, temperature, salt, and chelator.
- Halbrooks PJ, He QY, Briggs SK, Everse SJ, Smith VC, MacGillivray RT, Mason AB (April 2003). “Investigation of the mechanism of iron release from the C-lobe of human serum transferrin: mutational analysis of the role of a pH sensitive triad”. Biochemistry. 42 (13): 3701–7. doi:10.1021/bi027071q. PMID 12667060.
The receptor with its ligand bound transferrin 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+).
- Baker EN, Lindley PF (August 1992). “New perspectives on the structure and function of transferrins”. Journal of Inorganic Biochemistry. 47 (3–4): 147–60. doi:10.1016/0162-0134(92)84061-q. PMID 1431877.
Humans and other mammals
The liver is the main site of transferrin synthesis but other tissues and organs, including the brain, also produce transferrin. A major source of transferrin secretion in the brain is the choroid plexus in the ventricular system.
- Moos T (November 2002). “Brain iron homeostasis”. Danish Medical Bulletin. 49 (4): 279–301. PMID 12553165.
The main role of transferrin is to deliver iron from absorption centers in the duodenum and white blood cell macrophages to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur. The receptor helps maintain iron homeostasis in the cells by controlling iron concentrations.
- Macedo MF, de Sousa M (March 2008). “Transferrin and the transferrin receptor: of magic bullets and other concerns”. Inflammation & Allergy – Drug Targets. 7 (1): 41–52. doi:10.2174/187152808784165162. PMID 18473900.
The gene coding for transferrin in humans is located in chromosome band 3q21.
- Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, et al. (May 1984). “Human transferrin: cDNA characterization and chromosomal localization”. Proceedings of the National Academy of Sciences of the United States of America. 81 (9): 2752–6. Bibcode:1984PNAS…81.2752Y. doi:10.1073/pnas.81.9.2752. PMC 345148. PMID 6585826.
Medical professionals may check serum transferrin level in iron deficiency and in iron overload disorders such as hemochromatosis.
Other species
Drosophila melanogaster has three transferrin genes and is highly divergent from all other model clades, Ciona intestinalis one, Danio rerio has three highly divergent from each other, as do Takifugu rubripes and Xenopus tropicalis and Gallus gallus, while Monodelphis domestica has two divergent orthologs, and Mus musculus has two relatively close and one more distant ortholog. Relatedness and orthology/paralogy data are also available for Dictyostelium discoideum, Arabidopsis thaliana, and Pseudomonas aeruginosa.
- Gabaldón T, Koonin EV (May 2013). “Functional and evolutionary implications of gene orthology”. Nature Reviews. Genetics. Nature Portfolio. 14 (5): 360–6. doi:10.1038/nrg3456. PMC 5877793. PMID 23552219.
Structure
In humans, transferrin consists of a polypeptide chain containing 679 amino acids and two carbohydrate chains. The protein is composed of alpha helices and beta sheets that form two domains.
- “Transferrin Structure”. St. Edward’s University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.
- Dewan JC, Mikami B, Hirose M, Sacchettini JC (November 1993). “Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release”. Biochemistry. 32 (45): 11963–8. doi:10.1021/bi00096a004. PMID 8218271.
The amino acids which bind the iron ion to the transferrin are identical for both lobes; two tyrosines, one histidine, and one aspartic acid. For the iron ion to bind, an anion is required, preferably carbonate (CO2−3).
- “Transferrin Structure”. St. Edward’s University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
- Baker EN, Lindley PF (August 1992). “New perspectives on the structure and function of transferrins”. Journal of Inorganic Biochemistry. 47 (3–4): 147–60. doi:10.1016/0162-0134(92)84061-q. PMID 1431877.
Transferrin also has a transferrin iron-bound receptor; it is a disulfide-linked homodimer.
- Macedo MF, de Sousa M (March 2008). “Transferrin and the transferrin receptor: of magic bullets and other concerns”. Inflammation & Allergy – Drug Targets. 7 (1): 41–52. doi:10.2174/187152808784165162. PMID 18473900
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 atoms 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.
- “Transferrin Structure”. St. Edward’s University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
Two main transferrin receptors found in humans denoted as transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2). Although both are similar in structure, TfR1 can only bind specifically to human TF where TfR2 also has the capability to interact with bovine TF.
- Kawabata H (March 2019). “Transferrin and transferrin receptors update”. Free Radical Biology & Medicine. 133: 46–54. doi:10.1016/j.freeradbiomed.2018.06.037. PMID 29969719. S2CID 49674402
- Transferrin bound to its receptor.
- Transferrin receptor complex.
- PDB: 2nsu; Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC, Nelson CD, Bowman VD, Battisti AJ, Chipman PR, Parrish CR, Rossmann MG (Apr 2007). “Asymmetric binding of transferrin receptor to parvovirus capsids”. Proceedings of the National Academy of Sciences of the United States of America. 104 (16): 6585–9. Bibcode:2007PNAS..104.6585H. doi:10.1073/pnas.0701574104. PMC1871829. PMID17420467.
Immune system
Transferrin is also associated with the innate immune system. It is found in the 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.
- Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY (1999). “Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort”. Journal of Clinical Laboratory Analysis. 13 (6): 273–9. doi:10.1002/(SICI)1098-2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X. PMC 6808097. PMID 10633294.
Role in disease
An increased plasma transferrin level is often seen in patients with iron deficiency anemia, during pregnancy, and with the use of oral contraceptives, reflecting an increase in transferrin protein expression. When plasma transferrin levels rise, there is a reciprocal decrease in percent transferrin iron saturation, and a corresponding increase in total iron binding capacity in iron deficient states.
- Miller JL (July 2013). “Iron deficiency anemia: a common and curable disease”. Cold Spring Harbor Perspectives in Medicine. 3 (7): a011866. doi:10.1101/cshperspect.a011866. PMC 3685880. PMID 23613366.
A decreased plasma transferrin level can occur in iron overload diseases and protein malnutrition. An absence of transferrin results from a rare genetic disorder known as atransferrinemia, a condition characterized by anemia and hemosiderosis in the heart and liver that leads to heart failure and many other complications as well as to H63D syndrome.
Studies reveal that a transferrin saturation (serum iron concentration ÷ total iron binding capacity) over 60 percent in men and over 50 percent in women identified the presence of an abnormality in iron metabolism (Hereditary hemochromatosis, heterozygotes and homozygotes) with approximately 95 percent accuracy. This finding helps in the early diagnosis of Hereditary hemochromatosis, especially while serum ferritin still remains low. The retained iron in Hereditary hemochromatosis is primarily deposited in parenchymal cells, with reticuloendothelial cell accumulation occurring very late in the disease. This is in contrast to transfusional iron overload in which iron deposition occurs first in the reticuloendothelial cells and then in parenchymal cells. This explains why ferritin levels remain relatively low in Hereditary hemochromatosis, while transferrin saturation is high.
- Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS (July 2011). “Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases”. Hepatology. Baltimore, Md. 54 (1): 328–43. doi:10.1002/hep.24330. PMC 3149125. PMID 21452290.
- “Hemochromatosis”. guidelinecentral.com.
Transferrin and its receptor have been shown to diminish tumour cells when the receptor is used to attract antibodies.
- Macedo MF, de Sousa M (March 2008). “Transferrin and the transferrin receptor: of magic bullets and other concerns”. Inflammation & Allergy – Drug Targets. 7 (1): 41–52. doi:10.2174/187152808784165162. PMID 18473900.
Transferrin and nanomedicine
Many drugs are hindered when providing treatment when crossing the blood-brain barrier yielding poor uptake into areas of the brain. Transferrin glycoproteins are able to bypass the blood-brain barrier via receptor-mediated transport for specific transferrin receptors found in the brain capillary endothelial cells.
- Ghadiri M, Vasheghani-Farahani E, Atyabi F, Kobarfard F, Mohamadyar-Toupkanlou F, Hosseinkhani H (October 2017). “Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier”. Journal of Biomedical Materials Research Part A. 105 (10): 2851–2864. doi:10.1002/jbm.a.36145. PMID 28639394.
Due to this functionality, it is theorized that nanoparticles acting as drug carriers bound to transferrin glycoproteins can penetrate the blood-brain barrier allowing these substances to reach the diseased cells in the brain.
- Gaspar R (February 2013). “Nanoparticles: Pushed off target with proteins”. Nature Nanotechnology. 8 (2): 79–80. Bibcode:2013NatNa…8…79G. doi:10.1038/nnano.2013.11. PMID 23380930.
Advances with transferrin conjugated nanoparticles can lead to non-invasive drug distribution in the brain with potential therapeutic consequences of central nervous system (CNS) targeted diseases (e.g. Alzheimer’s or Parkinson’s disease).
- Li S, Peng Z, Dallman J, Baker J, Othman AM, Blackwelder PL, Leblanc RM (September 2016). “Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study”. Colloids and Surfaces. B, Biointerfaces. 145: 251–256. doi:10.1016/j.colsurfb.2016.05.007. PMID 27187189.
Other effects
Carbohydrate deficient transferrin (CDT aka desialotransferrin or asialotransferrin) increases in the blood with heavy ethanol consumption and can be monitored through laboratory testing.
- Sharpe PC (November 2001). “Biochemical detection and monitoring of alcohol abuse and abstinence”. Ann. Clin. Biochem. 38 (Pt 6): 652–64. doi:10.1258/0004563011901064. PMID 11732647.
Transferrin is a serum protein that carries iron through the bloodstream to the bone marrow, where red blood cells are manufactured, as well as to the liver and spleen. Structurally, transferrin is a polypeptide with two N-linked polysaccharide chains. These polysaccharide chains are branched with sialic acid residues. Sialic acid is a monosaccharide carbohydrate.
Note: Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
- Varki, Ajit; Roland Schauer (2008). “Sialic Acids”. in Essentials of Glycobiology. Cold Spring Harbor Press. pp. Ch. 14. ISBN 9780879697709.
The term “sialic acid” (from the Greek for saliva, σίαλον – síalon) was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is N-acetylneuraminic acid (Neu5Ac or NANA) found in animals and some prokaryotes. Sialic acids are found widely distributed in animal tissues and related forms are found to a lesser extent in other organisms like in some micro-algae, bacteria and archaea.
- Wagstaff, Ben (2018). “Identification of a Kdn biosynthesis pathway in the haptophyte Prymnesium parvum suggests widespread sialic acid biosynthesis among microalgae”. Journal of Biological Chemistry. 293 (42): 16277–16290. doi:10.1074/jbc.RA118.004921. PMC 6200933. PMID 30171074.
- Ajit, Varki (2017). “Sialic Acids and Other Nonulosonic Acids”. Sialic acids and other nonulosonic acids.” Essentials of Glycobiology. Cold Spring Harbor Laboratory Press. doi:10.1101/glycobiology.3e.015 (inactive 2023-06-13). PMID 28876847
- Kleikamp, Hugo (2020). “Tackling the chemical diversity of microbial nonulosonic acids – a universal large-scale survey approach”. Chemical Science. 11 (11): 3074–3080. doi:10.1039/c9sc06406k. PMC 8157484. PMID 34122812.
- Lewis, Amanda (2009). “Innovations in host and microbial sialic acid biosynthesis revealed by phylogenomic prediction of nonulosonic acid structure”. Proceedings of the National Academy of Sciences. 106 (32): 13552–13557. Bibcode:2009PNAS..10613552L. doi:10.1073/pnas.0902431106. PMC 2726416. PMID 19666579
- Schauer, Roland (2018). “Exploration of the Sialic Acid World”. Adv Carbohydr Chem Biochem. Advances in Carbohydrate Chemistry and Biochemistry. 75 (75): 1–213. doi:10.1016/bs.accb.2018.09.001. ISBN 9780128152027. PMC 7112061. PMID 30509400.
Sialic acids are commonly part of glycoproteins, glycolipids or gangliosides, where they decorate the end of sugar chains at the surface of cells or soluble proteins.
- Wang, B.; Brand-Miller, J. (2003). “The role and potential of sialic acid in human nutrition”. European Journal of Clinical Nutrition. 57 (11): 1351–1369. doi:10.1038/sj.ejcn.1601704. PMID 14576748.
However, sialic acids have been also observed in Drosophila embryos and other insects.
- Mandal, C. (1990). “Sialic acid binding lectins”. Experientia. 46 (5): 433–441. doi:10.1007/BF01954221. PMID 2189746. S2CID 27075067.
Generally, plants seem not to contain or display sialic acids.
- Varki, Ajit; Roland Schauer (2008). “Sialic Acids”. in Essentials of Glycobiology. Cold Spring Harbor Press. pp. Ch. 14. ISBN 9780879697709.
In humans the brain has the highest sialic acid content, where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis.
- Wang, B.; Brand-Miller, J. (2003). “The role and potential of sialic acid in human nutrition”. European Journal of Clinical Nutrition. 57 (11): 1351–1369. doi:10.1038/sj.ejcn.1601704. PMID 14576748.
More than 50 kinds of sialic acid are known, all of which can be obtained from a molecule of neuraminic acid by substituting its amino group or one of its hydroxyl groups.
- Varki, Ajit; Roland Schauer (2008). “Sialic Acids”. in Essentials of Glycobiology. Cold Spring Harbor Press. pp. Ch. 14. ISBN 9780879697709.
In general, the amino group bears either an acetyl or a glycolyl group, but other modifications have been described. These modifications along with linkages have shown to be tissue specific and developmentally regulated expressions, so some of them are only found on certain types of glycoconjugates in specific cells.
- Mandal, C. (1990). “Sialic acid binding lectins”. Experientia. 46 (5): 433–441. doi:10.1007/BF01954221. PMID 2189746. S2CID 27075067
The hydroxyl substituents may vary considerably; acetyl, lactyl, methyl, sulfate, and phosphate groups have been found.
- Schauer R. (2000). “Achievements and challenges of sialic acid research”. Glycoconj. J. 17 (7–9): 485–499. doi:10.1023/A:1011062223612. PMC 7087979. PMID 11421344.
The sialic acid family includes many derivatives of the nine-carbon sugar neuraminic acid, but these acids rarely appear free in nature. Normally they can be found as components of oligosaccharide chains of mucins, glycoproteins and glycolipids occupying terminal, nonreducing positions of complex carbohydrates on both external and internal membrane areas where they are very exposed and develop important functions.
- Wang, B.; Brand-Miller, J. (2003). “The role and potential of sialic acid in human nutrition”. European Journal of Clinical Nutrition. 57 (11): 1351–1369. doi:10.1038/sj.ejcn.1601704. PMID 14576748.
In contrast to other animals, humans are genetically unable to produce the sialic acid variant N-glycolylneuraminic acid (Neu5Gc). Small amounts of Neu5Gc detected in human tissue however may be incorporated from exogenous (nutrient) sources.
- Tangvoranuntakul, Pam (October 14, 2003). “Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid”. PNAS. 100 (21): 12045–12050. Bibcode:2003PNAS..10012045T. doi:10.1073/pnas.2131556100. PMC 218710. PMID 14523234.
Various forms of transferrin exist, with differing levels of sialylation. The most common form is tetrasialotransferrin, with four sialic acid chains. In persons who consume significant quantities of alcohol (usually more than 4 or 5 alcoholic beverages a day for two weeks or more) [citation needed], the proportion of transferrin with zero, one, or two sialic acid chains is increased. These are referred to as carbohydrate-deficient transferrins. These carbohydrate-deficient transferrins can be measured in the bloodstream and are important markers for alcohol use disorder. but elevated levels can also be found in a number of medical conditions. The limitations of the assay depend upon the methodology of the test. HPLC (High Performance Liquid Chromatography) can detect certain genetic variants and potential liver diseases affecting CDT.
- Sharpe PC (November 2001). “Biochemical detection and monitoring of alcohol abuse and abstinence”. Annals of Clinical Biochemistry. 38 (Pt 6): 652–64. doi:10.1258/0004563011901064. PMID 11732647.
Used with other tests, such as gamma glutamyl transferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), carbohydrate-deficient transferrin can be a useful tool in identifying problem drinking, such as alcohol use disorder. However, it is less sensitive than phosphatidylethanol (PEth) in detecting current regular alcohol consumption. The ethanol conjugates ethyl glucuronide and ethyl sulfate remain positive for up to three days after ethanol consumption and are quite useful for detection of occult/denied alcohol use disorder. Both these substances are detectable clinically through urine drug testing by commercial toxicology labs.
- Helander, A.; Peter, O.; Zheng, Y. (2012). “Monitoring of the Alcohol Biomarkers PEth, CDT and EtG/EtS in an Outpatient Treatment Setting”. Alcohol and Alcoholism. 47 (5): 552–557. doi:10.1093/alcalc/ags065. ISSN 0735-0414. PMID 22691387.
- Bell, H.; Tallaksen, C.; Sjahelm, T.; Weberg, R.; Raknerud, N.; Orjasaeter, H.; Try, K.; Haug, E. (1993). “Serum Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients with Chronic Liver Diseases”. Alcoholism: Clinical and Experimental Research. 17 (2): 246. doi:10.1111/j.1530-0277.1993.tb00757.x.
Transferrin is an acute phase protein and is seen to decrease in inflammation, cancers, and certain diseases (in contrast to other acute phase proteins, e.g., C-reactive protein, which increase in case of acute inflammation).
- Jain S, Gautam V, Naseem S (January 2011). “Acute-phase proteins: As diagnostic tool”. Journal of Pharmacy & Bioallied Sciences. 3 (1): 118–27. doi:10.4103/0975-7406.76489. PMC 3053509. PMID 21430962.
Pathology
Atransferrinemia is associated with a deficiency in transferrin.
Atransferrinemia is an autosomal recessive metabolic disorder in which there is an absence of transferrin, a plasma protein that transports iron through the blood.
- RESERVED, INSERM US14 — ALL RIGHTS. “Orphanet: Congenital atransferrinemia”. www.orpha.net. Retrieved 2017-02-20.][“OMIM Entry – # 209300 – ATRANSFERRINEMIA”. omim.org. Retrieved 19 February 2017.
Atransferrinemia is characterized by anemia and hemosiderosis in the heart and liver. The iron damage to the heart can lead to heart failure. The anemia is typically microcytic and hypochromic (the red blood cells are abnormally small and pale). Atransferrinemia was first described in 1961 and is extremely rare, with only ten documented cases worldwide.
- “Atransferrinemia”. National Organization for Rare Disorders. Retrieved 20 February 2017.
The presentation of this disorder entails anemia, arthritis, hepatic anomalies, and recurrent infections are clinical signs of the disease.
- “Atransferrinemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program”. rarediseases.info.nih.gov. Retrieved 2017-02-20.
Iron overload occurs mainly in the liver, heart, pancreas, thyroid, and kidney.
Barton, James C.; Edwards, Corwin Q. (2001). Hemochromatosis: Genetics, Pathophysiology, Diagnosis and Treatment. Cambridge University Press. p. 212. ISBN 9780521593809.
Transferrin is a serum transport protein that transports iron to the reticuloendothelial system for utilization and erythropoiesis, since there is no transferrin in atransferrinemia, serum free iron cannot reach reticuloendothelial cells and there is microcytic anemia.
- Bartnikas, Thomas Benedict (1 August 2012). “Known and potential roles of transferrin in iron biology”. BioMetals. 25 (4): 677–686. doi:10.1007/s10534-012-9520-3. PMC 3595092. PMID 22294463]
- Reference, Genetics Home. “TF gene”. Genetics Home Reference. Retrieved 2017-02-20.
- “OMIM Entry – * 190000 – TRANSFERRIN; TF”. omim.org. Retrieved 20 February 2017.
Also, this excess iron deposits itself in the heart, liver and joints, and causes damage. Ferritin, the storage form of iron gets secreted more into the bloodstream so as to bind with the excessive free iron and hence serum ferritin levels rise in this condition [medical citation needed] In terms of genetics of atransferrinemia researchers have identified mutations in the TF gene as a probable cause of this genetic disorder in affected people.
- RESERVED, INSERM US14 — ALL RIGHTS. “Orphanet: Congenital atransferrinemia”. www.orpha.net. Retrieved 2017-02-20.
There are two forms of this condition that causes an absence of transferrin in the affected individual:
- Marks, Vincent; Mesko, Dusan (2002). Differential Diagnosis by Laboratory Medicine: A Quick Reference for Physicians. Springer Science & Business Media. p. 633. ISBN 9783540430575. Retrieved 20 February 2017
Acquired atransferrinemia and Congenital atransferrinemia. The treatment of atransferrinemia is apotransferrin, the missing protein without iron. After the dissociation of iron, transferrin is called apotransferrin. Apotransferrin remains bound to its receptor because it has a high affinity for its receptors at a reduced pH. It recycles back to the plasma membrane, still bound to its receptor.
- Ogun AS, Adeyinka A. Biochemistry, Transferrin. [Updated 2022 Nov 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532928/
Iron treatment is detrimental as it does not correct the anemia and is a cause of secondary hemochromatosis.
- Hoffman, Ronald; Benz, Edward J. Jr.; Silberstein, Leslie E.; Heslop, Helen; Weitz, Jeffrey; Anastasi, John (2012). Hematology: Diagnosis and Treatment. Elsevier Health Sciences. p. 443. ISBN 978-1455740413.
- Gelderman MP, Baek JH, Yalamanoglu A, Puglia M, Vallelian F, Burla B, Vostal J, Schaer DJ, Buehler PW. Reversal of hemochromatosis by apotransferrin in non-transfused and transfused Hbbth3/+ (heterozygous B1/B2 globin gene deletion) mice. Haematologica. 2015 May;100(5):611-22. doi: 10.3324/haematol.2014.117325. Epub 2015 Jan 23. PMID: 25616571; PMCID: PMC4420210.
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.
- “Normal Reference Range Table”. Interactive Case Study Companion to Pathological Basis of Disease. The University of Texas Southwestern Medical Center at Dallas. Archived from the original on 2011-12-25. Retrieved 2008-10-25. Kumar V, Hagler HK (1999). Interactive Case Study Companion to Robbins Pathologic Basis of Disease (6th Edition (CD-ROM for Windows & Macintosh, Individual) ed.). W B Saunders Co. ISBN0-7216-8462-9.
A high transferrin level may indicate an 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. Low transferrin likely indicates malnutrition.
Interactions
Transferrin has been shown to interact with insulin-like growth factor 2 and IGFBP3.
- Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (December 2001). “Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3”. FEBS Letters. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962. S2CID 22895295.
- Weinzimer SA, Gibson TB, Collett-Solberg PF, Khare A, Liu B, Cohen P (April 2001). “Transferrin is an insulin-like growth factor-binding protein-3 binding protein”. The Journal of Clinical Endocrinology and Metabolism. 86 (4): 1806–13. doi:10.1210/jcem.86.4.7380. PMID 11297622.
Transcriptional regulation of transferrin is upregulated by retinoic acid.
- Hsu SL, Lin YF, Chou CK (April 1992). “Transcriptional regulation of transferrin and albumin genes by retinoic acid in human hepatoma cell line Hep3B”. The Biochemical Journal. 283 ( Pt 2) (2): 611–5. doi:10.1042/bj2830611. PMC 1131079. PMID 1315521.
Related proteins
Members of the family include blood serotransferrin (or siderophilin, usually simply called transferrin); LACTOTRANSFERRIN (lactoferrin); MILK transferrin; egg white ovotransferrin (conalbumin); AND membrane-associated melanotransferrin.
- Chung MC (October 1984). “Structure and function of transferrin”. Biochemical Education. 12 (4): 146–154. doi:10.1016/0307-4412(84)90118-3.
Note: Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions. Lactoferrin is also present in secondary granules of PMNs and is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum (“first milk”) has the highest concentration, followed by human milk, then cow milk (150 mg/L). Lactoferrin is one of the components of the immune system of the body; it has antimicrobial activity (bacteriocide, fungicide) and is part of the innate defense, mainly at mucoses.
- Sánchez L, Calvo M, Brock JH (May 1992). “Biological role of lactoferrin”. Archives of Disease in Childhood. 67 (5): 657–61. doi:10.1136/adc.67.5.657. PMC 1793702. PMID 1599309.
In particular, lactoferrin provides antibacterial activity to human infants.
- [Levin RE, Kalidas S, Gopinadhan P, Pometto A (2006). Food biotechnology. Boca Raton, FL: CRC/Taylor & Francis. p. 1028. ISBN 978-0-8247-5329-0.][Pursel VG (1998). “Modification of Production Traits”. In Clark AJ (ed.). Animal Breeding: Technology for the 21st Century (Modern Genetics). Boca Raton: CRC. p. 191. ISBN 978-90-5702-292-0.
Lactoferrin interacts with DNA and RNA, polysaccharides and heparin, and shows some of its biological functions in complexes with these ligands. Occurrence of iron-containing red protein in bovine milk was reported as early as in 1939; however, the protein could not be properly characterized because it could not be extracted with sufficient purity. Its first detailed studies were reported around 1960. They documented the molecular weight, isoelectric point, optical absorption spectra and presence of two iron atoms per protein molecule.
- M. Sorensen and S. P. L. Sorensen, Compf. rend. trav. lab. Carlsberg (1939) 23, 55, cited by Groves (1960)
- Groves ML (1960). “The Isolation of a Red Protein from Milk”. Journal of the American Chemical Society. 82 (13): 3345. doi:10.1021/ja01498a029.
- Johansson B, Virtanen AI, Tweit RC, Dodson RM (1960). “Isolation of an iron-containing red protein from human milk” (PDF). Acta Chem. Scand. 14 (2): 510–512. doi:10.3891/acta.chem.scand.14-0510.]
The protein was extracted from milk, contained iron and was structurally and chemically similar to serum transferrin. Therefore, it was named lactoferrin in 1961, though the name lactotransferrin was used in some earlier publications, and later studies demonstrated that the protein is not restricted to milk. The antibacterial action of lactoferrin was also documented in 1961 and was associated with its ability to bind iron.
- Naidu AS (2000). Lactoferrin: natural, multifunctional, antimicrobial. Boca Raton: CRC Press. pp. 1–2. ISBN 978-0-8493-0909-0.
Note: Ovotransferrin (conalbumin) is a glycoprotein of egg white albumen.
- “OVOTRANSFERRIN: The nutraceutical protein with antimicrobial, antioxidant and immunomodulatory properties”. Bioseutica B.V.
Egg white albumen is composed of multiple proteins, of which ovotransferrin is the most heat reliable. It has a molecular weight of 76,000 daltons and contains about 700 amino acids. Ovotransferrin makes up approximately 13% of egg albumen (in contrast to ovalbumin, which comprises 54%).
- Wu J, Acero-Lopez A (2012). “Ovotransferrin: Structure, bioactivities, and preparation”. Food Research International. 46 (2): 480–487. doi:10.1016/j.foodres.2011.07.012.
As a member of the transferrin and metalloproteinase family, ovotransferrin has been found to possess antibacterial and antioxydant and immunomodulatory properties, arising primarily through its iron (Fe3+) binding capacity by locking away a key biochemical component necessary for micro-organismal survival. Bacteria starved of iron are rendered incapable of moving, making ovotransferrin a potent bacteriostatic.
Note: Melanotransferrin is a protein that in humans is encoded by the MFI2 gene. MFI2 has also recently been designated CD228 (cluster of differentiation 228). The protein encoded by this gene is a cell-surface glycoprotein found on melanoma cells. The protein shares sequence similarity and iron-binding properties with members of the transferrin superfamily. The importance of the iron binding function has not yet been identified. This gene resides in the same region of chromosome 3 as members of the transferrin superfamily. Alternative splicing results in two transcript variants.
It is part of neural crest tissue, often present in melanotic neuroectodermal tumor of infancy. This tumor is extremely rare, with fewer than 500 cases reported worldwide. More than 95% of patients are less than 1 year of age at presentation, with about 80% less than 6 months. Females are affected more often than males (2:1)
Melanotic neuroectodermal tumor of infancy is a very rare oral cavity tumor that is seen in patients usually at or around birth. It must be removed to be cured. Definitions: A rare, biphasic, neuroblastic, and pigmented epithelial neoplasm of craniofacial sites, usually involving the oral cavity or gums. It is considered to be a developmental anomaly, and thus is congenital in presentation. It is thought to be derived from neural crest, which is one of the embryologic tissue types. The reason for this postulation is based on the expression of melanotransferrin (melanoma-specific peptide that may play role in iron metabolism).
Differential diagnoses
It is important in this age group to exclude other tumors that can have a similar appearance, such as rhabdomyosarcoma, lymphoma, Ewing sarcoma (primitive neuroectodermal tumor), or even a melanoma (although they are very rare in infants).
- Selim H, Shaheen S, Barakat K, Selim AA (June 2008). “Melanotic neuroectodermal tumor of infancy: review of literature and case report”. J Pediatr Surg. 43 (6): E25–9. doi:10.1016/j.jpedsurg.2008.02.068. PMID 18558161.
- Nelson BL, Thompson LD (June 2006). “Melanotic neuroectodermal tumor of infancy”. Ear Nose Throat J. 85 (6): 365. doi:10.1177/014556130608500608. PMID 16866106. S2CID 31516123.
- Marston AP, Black A, Pambuccian SE, Hamlar DD (July 2014). “Mass originating from the maxillary alveolar crest in an infant”. JAMA Otolaryngol Head Neck Surg. 140 (7): 667–8. doi:10.1001/jamaoto.2014.632. PMID 24810545.
- Gaiger de Oliveira M, Thompson LD, Chaves AC, Rados PV, da Silva Lauxen I, Filho MS (August 2004). “Management of melanotic neuroectodermal tumor of infancy”. Ann Diagn Pathol. 8 (4): 207–12. doi:10.1053/j.anndiagpath.2004.04.003. PMID 15290671.]
Further reading
Lester D. R. Thompson; Bruce M. Wenig (2016). Diagnostic Pathology: Head and Neck, 2nd edition. Elsevier. ISBN 978-0323392556.
See also
- Beta-2 transferrin
- Transferrin receptor
- Total iron-binding capacity
- Transferrin saturation
- Ferritin
- Optiferrin recombinant human transferrin
- Atransferrinemia
- Hypotransferrinemia
- HFE H63D gene mutation
References
- GRCh38: Ensembl release 89: ENSG00000091513 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000032554 – Ensembl, May 2017
- “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
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- Kawabata H (March 2019). “Transferrin and transferrin receptors update”. Free Radical Biology & Medicine. 133: 46–54. doi:10.1016/j.freeradbiomed.2018.06.037. PMID 29969719. S2CID 49674402.
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- Dewan JC, Mikami B, Hirose M, Sacchettini JC (November 1993). “Structural evidence for a pH-sensitive dilysine trigger in the hen ovotransferrin N-lobe: implications for transferrin iron release”. Biochemistry. 32 (45): 11963–8. doi:10.1021/bi00096a004. PMID 8218271.
- Baker EN, Lindley PF (August 1992). “New perspectives on the structure and function of transferrins”. Journal of Inorganic Biochemistry. 47 (3–4): 147–60. doi:10.1016/0162-0134(92)84061-q. PMID 1431877.
- Halbrooks PJ, He QY, Briggs SK, Everse SJ, Smith VC, MacGillivray RT, Mason AB (April 2003). “Investigation of the mechanism of iron release from the C-lobe of human serum transferrin: mutational analysis of the role of a pH sensitive triad”. Biochemistry. 42 (13): 3701–7. doi:10.1021/bi027071q. PMID 12667060.
- Moos T (November 2002). “Brain iron homeostasis”. Danish Medical Bulletin. 49 (4): 279–301. PMID 12553165.
- Macedo MF, de Sousa M (March 2008). “Transferrin and the transferrin receptor: of magic bullets and other concerns”. Inflammation & Allergy – Drug Targets. 7 (1): 41–52. doi:10.2174/187152808784165162. PMID 18473900.
- Gabaldón T, Koonin EV (May 2013). “Functional and evolutionary implications of gene orthology”. Nature Reviews. Genetics. Nature Portfolio. 14 (5): 360–6. doi:10.1038/nrg3456. PMC 5877793. PMID 23552219.
- “Transferrin Structure”. St. Edward’s University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
- PDB: 1suv; Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (Feb 2004). “Structure of the human transferrin receptor-transferrin complex”. Cell. 116 (4): 565–76. doi:10.1016/S0092-8674(04)00130-8. PMID 14980223. S2CID 2981917.
- PDB: 2nsu; Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC, Nelson CD, Bowman VD, Battisti AJ, Chipman PR, Parrish CR, Rossmann MG (Apr 2007). “Asymmetric binding of transferrin receptor to parvovirus capsids”. Proceedings of the National Academy of Sciences of the United States of America. 104 (16): 6585–9. Bibcode:2007PNAS..104.6585H. doi:10.1073/pnas.0701574104. PMC 1871829. PMID 17420467.
- Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY (1999). “Reference distributions for the negative acute-phase serum proteins, albumin, transferrin and transthyretin: a practical, simple and clinically relevant approach in a large cohort”. Journal of Clinical Laboratory Analysis. 13 (6): 273–9. doi:10.1002/(SICI)1098-2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X. PMC 6808097. PMID 10633294.
- Miller JL (July 2013). “Iron deficiency anemia: a common and curable disease”. Cold Spring Harbor Perspectives in Medicine. 3 (7): a011866. doi:10.1101/cshperspect.a011866. PMC 3685880. PMID 23613366.
- Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS (July 2011). “Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases”. Hepatology. Baltimore, Md. 54 (1): 328–43. doi:10.1002/hep.24330. PMC 3149125. PMID 21452290.
- “Hemochromatosis”. guidelinecentral.com.
- Ghadiri M, Vasheghani-Farahani E, Atyabi F, Kobarfard F, Mohamadyar-Toupkanlou F, Hosseinkhani H (October 2017). “Transferrin-conjugated magnetic dextran-spermine nanoparticles for targeted drug transport across blood-brain barrier”. Journal of Biomedical Materials Research Part A. 105 (10): 2851–2864. doi:10.1002/jbm.a.36145. PMID 28639394.
- Gaspar R (February 2013). “Nanoparticles: Pushed off target with proteins”. Nature Nanotechnology. 8 (2): 79–80. Bibcode:2013NatNa…8…79G. doi:10.1038/nnano.2013.11. PMID 23380930.
- Li S, Peng Z, Dallman J, Baker J, Othman AM, Blackwelder PL, Leblanc RM (September 2016). “Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study”. Colloids and Surfaces. B, Biointerfaces. 145: 251–256. doi:10.1016/j.colsurfb.2016.05.007. PMID 27187189.
- Sharpe PC (November 2001). “Biochemical detection and monitoring of alcohol abuse and abstinence”. Annals of Clinical Biochemistry. 38 (Pt 6): 652–64. doi:10.1258/0004563011901064. PMID 11732647.
- Jain S, Gautam V, Naseem S (January 2011). “Acute-phase proteins: As diagnostic tool”. Journal of Pharmacy & Bioallied Sciences. 3 (1): 118–27. doi:10.4103/0975-7406.76489. PMC 3053509. PMID 21430962.
- “Normal Reference Range Table”. Interactive Case Study Companion to Pathological Basis of Disease. The University of Texas Southwestern Medical Center at Dallas. Archived from the original on 2011-12-25. Retrieved 2008-10-25.
Kumar V, Hagler HK (1999). Interactive Case Study Companion to Robbins Pathologic Basis of Disease (6th Edition (CD-ROM for Windows & Macintosh, Individual) ed.). W B Saunders Co. ISBN 0-7216-8462-9. - Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (December 2001). “Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3”. FEBS Letters. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962. S2CID 22895295.
- Weinzimer SA, Gibson TB, Collett-Solberg PF, Khare A, Liu B, Cohen P (April 2001). “Transferrin is an insulin-like growth factor-binding protein-3 binding protein”. The Journal of Clinical Endocrinology and Metabolism. 86 (4): 1806–13. doi:10.1210/jcem.86.4.7380. PMID 11297622.
- Hsu SL, Lin YF, Chou CK (April 1992). “Transcriptional regulation of transferrin and albumin genes by retinoic acid in human hepatoma cell line Hep3B”. The Biochemical Journal. 283 ( Pt 2) (2): 611–5. doi:10.1042/bj2830611. PMC 1131079. PMID 1315521.
- Chung MC (October 1984). “Structure and function of transferrin”. Biochemical Education. 12 (4): 146–154. doi:10.1016/0307-4412(84)90118-3.
Further reading
- Hershberger CL, Larson JL, Arnold B, Rosteck PR, Williams P, DeHoff B, et al. (December 1991). “A cloned gene for human transferrin”. Annals of the New York Academy of Sciences. 646 (1): 140–54. Bibcode:1991NYASA.646..140H. doi:10.1111/j.1749-6632.1991.tb18573.x. PMID 1809186. S2CID 19519911.
- Bowman BH, Yang FM, Adrian GS (1989). Transferrin: evolution and genetic regulation of expression. Advances in Genetics. Vol. 25. pp. 1–38. doi:10.1016/S0065-2660(08)60457-5. ISBN 9780120176250. PMID 3057819.
- Parkkinen J, von Bonsdorff L, Ebeling F, Sahlstedt L (August 2002). “Function and therapeutic development of apotransferrin”. Vox Sanguinis. 83 Suppl 1 (Suppl 1): 321–6. doi:10.1111/j.1423-0410.2002.tb05327.x. PMID 12617162. S2CID 5876134.
External links
- Transferrin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P02787 (Serotransferrin) at the PDBe-KB.