Birth Control, Blood, Carrier Proteins, Cattle, Enzymes, Heparin, Iron, Metals, Neuroscience, Proteins, Reproduction, Zinc
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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.

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.

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.

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.

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.

For example, flavin and heme cofactors are often involved in redox reactions.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

However, sialic acids have been also observed in Drosophila embryos and other insects.

Generally, plants seem not to contain or display sialic acids.

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.

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.

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.

The hydroxyl substituents may vary considerably; acetyl, lactyl, methyl, sulfate, and phosphate groups have been found.

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.

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.

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.

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. 

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).

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.

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.

The presentation of this disorder entails anemia, arthritis, hepatic anomalies, and recurrent infections are clinical signs of the disease.

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.

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.

There are two forms of this condition that causes an absence of transferrin in the affected individual:

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.

Transcriptional regulation of transferrin is upregulated by retinoic acid.

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.

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.

In particular, lactoferrin provides antibacterial activity to human infants.

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.

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.

Note: Ovotransferrin (conalbumin) is a glycoprotein of egg white albumen.

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).

Further reading

Lester D. R. Thompson; Bruce M. Wenig (2016). Diagnostic Pathology: Head and Neck, 2nd edition. Elsevier. ISBN 978-0323392556.

See also

References

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  2. GRCm38: Ensembl release 89: ENSMUSG00000032554 – Ensembl, May 2017
  3. “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
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  8. 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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Further reading

External links

Carrier proteins, metalloproteins: Non-heme iron protein
Globular proteins
Acute-phase proteins
Metabolism: Metal metabolism

Categories: 

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