Transferrin

Source: Wikipedia, the free encyclopedia.
TF
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000091513

ENSMUSG00000032554

UniProt

P02787

Q921I1

RefSeq (mRNA)

NM_001063
NM_001354704
NM_001354703

NM_133977

RefSeq (protein)

NP_001054
NP_001341633
NP_001341632

NP_598738

Location (UCSC)Chr 3: 133.75 – 133.8 MbChr 9: 103.08 – 103.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Transferrin
Identifiers
SymbolTransferrin
SCOP2
1lcf / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Transferrins are

Fe3+ ions.[6] Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.[7][8]

Transferrin

association constant is 1020 M−1 at pH 7.4)[9] but decreases progressively with decreasing pH below neutrality. Transferrins are not limited to only binding to iron but also to different metal ions.[10] These glycoproteins are located in various bodily fluids of vertebrates.[11][12] Some invertebrates have proteins that act like transferrin found in the hemolymph.[11][13]

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

apoprotein
).

Occurrence and function

Transferrins are glycoproteins that are often found in biological fluids of vertebrates. When a transferrin protein loaded with iron encounters a

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+
).[13]

Humans and other mammals

The

macrophages to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur.[16] The receptor helps maintain iron homeostasis in the cells by controlling iron concentrations.[16]

The gene coding for transferrin in humans is located in chromosome band 3q21.[7]

Medical professionals may check serum transferrin level in

hemochromatosis
.

Other species

paralogy data are also available for Dictyostelium discoideum, Arabidopsis thaliana, and Pseudomonas aeruginosa.[17]

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.[18] The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.[12]

The

anion is required, preferably carbonate (CO2−
3).[18][13]

Transferrin also has a transferrin iron-bound

homodimer.[16] 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.[18] 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.[8]

  • Transferrin bound to its receptor.[19]
    Transferrin bound to its receptor.[19]
  • Transferrin receptor complex.[20]
    Transferrin receptor complex.[20]

Immune system

Transferrin is also associated with 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.[21]

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[22]

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 relative low in Hereditary hemochromatosis, while transferrin saturation is high.[23][24]

Transferrin and its receptor have been shown to diminish

antibodies.[16]

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.[25] 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.[26] 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).[27]

Other effects

Carbohydrate deficient transferrin increases in the blood with heavy ethanol consumption and can be monitored through laboratory testing.[28]

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).[29]

Pathology

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.[30] Laboratory test results should always be interpreted using the reference range provided by the laboratory that performed the test[citation needed].

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 an

interpretation of TIBC. Low transferrin likely indicates malnutrition
.

Interactions

Transferrin has been shown to

interact with insulin-like growth factor 2[31] and IGFBP3.[32] Transcriptional regulation of transferrin is upregulated by retinoic acid.[33]

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.[34]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000091513 – Ensembl, May 2017
  2. ^ a b c 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.
  5. PMID 3032619
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  6. PMID 11752780
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  7. ^
    PMID 6585826
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  8. ^
    S2CID 49674402
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  9. PMID 204636
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  10. S2CID 13929228
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  11. ^
    PMID 9609685
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  12. ^
    PMID 8218271
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  13. ^
    PMID 1431877
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  14. ^
    PMID 12667060
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  15. PMID 12553165
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  16. ^
    PMID 18473900
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  17. PMID 23552219
    .
  18. ^ a b c "Transferrin Structure". St. Edward's University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
  19. S2CID 2981917
    .
  20. PMID 17420467
    .
  21. PMID 10633294
    .
  22. PMID 23613366
    .
  23. PMID 21452290
    .
  24. ^ "Hemochromatosis". guidelinecentral.com.
  25. PMID 28639394
    .
  26. PMID 23380930
    .
  27. PMID 27187189
    .
  28. S2CID 12203099
    .
  29. PMID 21430962
    .
  30. ISBN 0-7216-8462-9
    .
  31. S2CID 22895295
    .
  32. PMID 11297622
    .
  33. PMID 1315521
    .
  34. doi:10.1016/0307-4412(84)90118-3
    .

Further reading

External links
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