Transferrin: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
{{Pfam_box
| update_page = yes
| Symbol = Transferrin
| require_manual_inspection = no
| Name = Transferrin
| update_protein_box = yes
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| caption =
| Pfam= PF00405
| InterPro= IPR001156
| SMART=
| Prosite = PDOC00182
| SCOP = 1lcf
| TCDB =
| OPM family= 161
| OPM protein= 1lfc
| PDB=
}}
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
'''Transferrins''' are iron-binding [[blood plasma]] [[glycoprotein]]s that control the level of free [[iron|iron (Fe)]] in [[biological fluids]].<ref name="PUB00001349">{{cite journal | vauthors = Crichton RR, Charloteaux-Wauters M | title = Iron transport and storage | journal = European Journal of Biochemistry / FEBS | volume = 164 | issue = 3 | pages = 485–506 | date = May 1987 | pmid = 3032619 | doi = 10.1111/j.1432-1033.1987.tb11155.x }}</ref> Human transferrin is encoded by the ''TF'' [[gene]].<ref name="pmid6585826">{{cite journal | vauthors = Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, Baldwin WD, Bowman BH | title = Human transferrin: cDNA characterization and chromosomal localization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 9 | pages = 2752–6 | date = May 1984 | pmid = 6585826 | pmc = 345148 | doi = 10.1073/pnas.81.9.2752 }}</ref>
{{GNF_Protein_box
 
| image = PBB_Protein_TF_image.jpg
Transferrin [[glycoprotein]]s bind iron tightly, but reversibly. Although iron bound to transferrin is less than 0.1% (4&nbsp;mg) of total body iron, it forms the most vital iron pool with the highest rate of turnover (25&nbsp;mg/24 h). Transferrin has a molecular weight of around 80 [[atomic mass unit|KDa]] and contains two specific high-affinity [[Fe(III)]] binding sites. The affinity of transferrin for Fe(III) is extremely high ([[association constant]] is 10<sup>20</sup> M<sup>−1</sup> at pH 7.4)<ref name="pmid204636">{{cite journal | vauthors = Aisen P, Leibman A, Zweier J | title = Stoichiometric and site characteristics of the binding of iron to human transferrin | journal = The Journal of Biological Chemistry | volume = 253 | issue = 6 | pages = 1930–7 | date = Mar 1978 | pmid = 204636 | doi =  | url = http://www.jbc.org/content/253/6/1930.full.pdf+html?sid=995cd8a1-154f-46dd-85ee-1e33f3eedcc4 }}</ref> but decreases progressively with decreasing [[pH]] below neutrality.
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1a8e.
| PDB = {{PDB2|1a8e}}, {{PDB2|1a8f}}, {{PDB2|1b3e}}, {{PDB2|1bp5}}, {{PDB2|1btj}}, {{PDB2|1d3k}}, {{PDB2|1d4n}}, {{PDB2|1dtg}}, {{PDB2|1fqe}}, {{PDB2|1fqf}}, {{PDB2|1jqf}}, {{PDB2|1n7w}}, {{PDB2|1n7x}}, {{PDB2|1n84}}, {{PDB2|1oqg}}, {{PDB2|1oqh}}, {{PDB2|1ryo}}, {{PDB2|1suv}}, {{PDB2|2hau}}, {{PDB2|2hav}}, {{PDB2|2o7u}}, {{PDB2|2o84}}
| Name = Transferrin
| HGNCid = 11740
| Symbol = TF
| AltSymbols =; DKFZp781D0156; PRO1557; PRO2086
| OMIM = 190000
| ECnumber =
| Homologene = 68153
| MGIid = 98821
| GeneAtlas_image1 = PBB_GE_TF_203400_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TF_214063_s_at_tn.png
| Function = {{GNF_GO|id=GO:0008199 |text = ferric iron binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005768 |text = endosome}} {{GNF_GO|id=GO:0030139 |text = endocytic vesicle}}
| Process = {{GNF_GO|id=GO:0006811 |text = ion transport}} {{GNF_GO|id=GO:0006826 |text = iron ion transport}} {{GNF_GO|id=GO:0006879 |text = cellular iron ion homeostasis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7018
    | Hs_Ensembl = ENSG00000091513
    | Hs_RefseqProtein = NP_001054
    | Hs_RefseqmRNA = NM_001063
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 134947925
    | Hs_GenLoc_end = 134980325
    | Hs_Uniprot = P02787
    | Mm_EntrezGene = 22041
    | Mm_Ensembl = ENSMUSG00000032554
    | Mm_RefseqmRNA = NM_133977
    | Mm_RefseqProtein = NP_598738
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 103067024
    | Mm_GenLoc_end = 103088436
    | Mm_Uniprot = Q3UBW7
  }}
}}
'''Transferrin''' is a [[blood plasma]] [[protein]] for [[iron]] [[ion]] delivery. Transferrin is a [[glycoprotein]], which binds iron very tightly but reversibly. Although iron bound to transferrin is less than 0.1% (4 mg) of the total body iron, dynamically 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 (10^23 M^-1 at pH 7.4) but decreases progressively with decreasing pH below neutrality.


When not bound to iron, it is known as "apotransferrin" (see also [[apoprotein]]).
When not bound to iron, transferrin is known as "apotransferrin" (see also [[Apoenzyme#Cofactors|apoprotein]]).


== Transport mechanism ==
== Transport mechanism ==


When a transferrin protein loaded with iron encounters a [[transferrin receptor]] on the surface of a [[cell (biology)|cell]] (importantly, to erythroid precursors in the bone marrow), it binds to it and is consequently transported into the cell in a [[vesicle (biology)|vesicle]]. The cell will acidify the vesicle, causing transferrin to release its iron ions. The receptor is then transported through the [[endocytic cycle]] back to the cell surface, ready for another round of iron uptake.
When a transferrin protein loaded with iron encounters a [[transferrin receptor]] on the surface of a [[cell (biology)|cell]], e.g., erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a [[vesicle (biology)|vesicle]] by [[receptor-mediated endocytosis]]. The pH of the vesicle is reduced by hydrogen ion pumps ([[V-ATPase|{{chem|H|+}} ATPases]]) to about 5.5, causing transferrin to release its iron ions. 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+).
Each transferrin molecule has the ability to carry two iron ions in the [[ferric]] form ({{chem|Fe|3+}}).
 
The [[gene]] coding for transferrin in humans is located in [[chromosome]] band 3q21.<ref name="pmid6585826"/>


The [[gene]] coding for transferrin in humans is located in [[chromosome]] band 3q21. Research on [[King snake|king snakes]] by Dessauer and Zwiefel in 1981 revealed the the inheritance of transferrin is a [[codominant]] trait.
Medical professionals may check serum transferrin level in [[Iron deficiency (medicine)|iron deficiency]] and in [[iron overload disorder]]s such as [[hemochromatosis]].


Transferrin levels may be checked in [[iron deficiency]], [[hemochromatosis]] and other [[iron overload disorder]]s.
==Structure==
 
In humans, transferrin consists of a polypeptide chain containing 679 [[amino acids]] and two carbohydrate chains. The protein is composed of [[alpha helix|alpha helices]] and [[beta sheet]]s that form two [[protein domain|domains]].<ref name="stedwards">{{cite web | url = http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Projects04/Transferrin/structure.htm | title = Transferrin Structure | date = 2005-07-18 | publisher = St. Edward's University | accessdate = 2009-04-24 | deadurl = yes | archiveurl = https://archive.is/20121211180614/http://www.cs.stedwards.edu/chem/Chemistry/CHEM43/CHEM43/Projects04/Transferrin/structure.htm | archivedate = 2012-12-11 | df =  }}</ref> 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]]. For the iron ion to bind, an [[anion]] is required, preferably [[carbonate]] ({{chem|CO|3|2−}}).<ref name="stedwards"/>
 
Transferrin also has a transferrin iron-bound [[receptor (biochemistry)|receptor]]; it is a disulfide-linked [[homodimer]].<ref name="pmid18473900">{{cite journal | vauthors = Macedo MF, de Sousa M | title = Transferrin and the transferrin receptor: of magic bullets and other concerns | journal = Inflammation & Allergy Drug Targets | volume = 7 | issue = 1 | pages = 41–52 | date = Mar 2008 | pmid = 18473900 | doi = 10.2174/187152808784165162 | url = http://www.bentham-direct.org/pages/content.php?IADT/2008/00000007/00000001/0007L.SGM }}</ref> 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.<ref name="stedwards"/>
 
<gallery>
Image:PDB_1suv_EBI.jpg|Transferrin bound to its receptor.<ref name="pmid14980223">{{PDB|1suv}}; {{cite journal | vauthors = Cheng Y, Zak O, Aisen P, Harrison SC, Walz T | title = Structure of the human transferrin receptor-transferrin complex | journal = Cell | volume = 116 | issue = 4 | pages = 565–76 | date = Feb 2004 | pmid = 14980223 | doi = 10.1016/S0092-8674(04)00130-8 }}</ref>
Image:PDB_2nsu_EBI.jpg|Transferrin receptor complex.<ref name="pmid17420467">{{PDB|2nsu}}; {{cite journal | vauthors = Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC, Nelson CD, Bowman VD, Battisti AJ, Chipman PR, Parrish CR, Rossmann MG | title = Asymmetric binding of transferrin receptor to parvovirus capsids | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 16 | pages = 6585–9 | date = Apr 2007 | pmid = 17420467 | pmc = 1871829 | doi = 10.1073/pnas.0701574104 }}</ref>
</gallery>
 
== Tissue distribution ==
 
The [[liver]] is the main site of transferrin synthesis but other tissues and organs, including the brain, also produce transferrin. The main role of transferrin is to deliver iron from absorption centers in the [[duodenum]] and white blood cell [[macrophages]] to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur.<ref name="pmid18473900"/> The receptor helps maintain iron [[homeostasis]] in the cells by controlling iron concentrations.<ref name="pmid18473900"/>


== Immune system ==
== 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.
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.<ref name=Ritchie>{{cite journal | vauthors = Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY | title = 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 = Journal of Clinical Laboratory Analysis | volume = 13 | issue = 6 | pages = 273–9 | year = 1999 | pmid = 10633294 | doi = 10.1002/(SICI)1098-2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X }}</ref>
 
==Role in disease==
 
An increased plasma transferrin level is often seen in patients suffering from 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|total iron binding capacity]] in iron deficient states<ref>{{cite journal | vauthors = Miller JL | year = 2013 | title = Iron Deficiency Anemia: A Common and Curable Disease | url = | journal = Cold Spring Harbor perspectives in medicine | volume =  3| issue = | page =  a011866| doi = 10.1101/cshperspect.a011866 }}</ref> A decreased plasma transferrin can occur in iron overload diseases and protein malnutrition. An absence of transferrin results from a rare genetic disorder known as [[atransferrinemia]], a condition characterized by anemia and [[hemosiderosis]] in the heart and liver that leads to heart failure and many other complications.


A decrease in the amount of transferrin would result in hemosiderin in the liver.
Transferrin and its receptor have been shown to diminish [[tumour cells]] when the receptor is used to attract [[antibodies]].<ref>{{cite journal|last1=Macedo|first1=Maria F.|last2=de Sousa|first2=Maria|title=Transferrin and the transferrin receptor: of magic bullets and other concerns|website=Inflammation & Allergy Drug Targets|pages=41–52|date=NaN|pmid=18473900|volume=7|doi=10.2174/187152808784165162}}</ref>


== Other effects ==
== Other effects ==


The metal binding properties of transferrin have a great influence on the biochemistry of [[plutonium]] in humans.
[[Carbohydrate deficient transferrin]] increases in the blood with heavy [[ethanol]] consumption and can be monitored through laboratory testing.<ref name="pmid11732647">{{cite journal|vauthors=Sharpe PC |title=Biochemical detection and monitoring of alcohol abuse and abstinence |journal=Annals of Clinical Biochemistry |volume=38 |issue=Pt 6 |pages=652–64 |date=Nov 2001 |pmid=11732647 |doi=10.1258/0004563011901064 |url=http://acb.rsmjournals.com/cgi/pmidlookup?view=long&pmid=11732647 }}{{dead link|date=November 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
Transferrin has a bacteriocidal effect on bacteria, in that it makes Fe3+ unavailable to the bacteria.
 
Transferrin is an acute phase protein and is therefore seen to decrease in inflammation, cancers, and certain diseases.<ref name="pmid21430962">{{cite journal | vauthors = Jain S, Gautam V, Naseem S | title = Acute-phase proteins: As diagnostic tool | journal = Journal of Pharmacy & Bioallied Sciences | volume = 3 | issue = 1 | pages = 118–27 | date = Jan 2011 | pmid = 21430962 | pmc = 3053509 | doi = 10.4103/0975-7406.76489 }}</ref>
 
== 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 ranges for blood tests#Electrolytes and Metabolites|reference range]] for transferrin is 204–360&nbsp;mg/dL.<ref name="southwest">{{cite web|url=http://pathcuric1.swmed.edu/PathDemo/nrrt.htm |title=Normal Reference Range Table |work=Interactive Case Study Companion to Pathlogical Basis of Disease |publisher=The University of Texas Southwestern Medical Center at Dallas |accessdate=2008-10-25 |deadurl=yes |archiveurl=https://web.archive.org/web/20111225185659/http://pathcuric1.swmed.edu/PathDemo/nrrt.htm |archivedate=2011-12-25 |df= }}<br/>{{cite book | author = Kumar V, Hagler HK | title = Interactive Case Study Companion to Robbins Pathologic Basis of Disease | edition = 6th Edition (CD-ROM for Windows & Macintosh, Individual) | publisher = W B Saunders Co | year = 1999 | isbn = 0-7216-8462-9 }}</ref> Laboratory test results should always be interpreted using the reference range provided by the laboratory that performed the test.


==Pathology==
[[File:Blood values sorted by mass and molar concentration.png|thumb|550px|left|[[Reference ranges for blood tests]], comparing blood content of transferrin and other iron-related compounds (shown in brown and orange) with other constituents]]
A deficiency is associated with [[atransferrinemia]].


==See also==
{{Clear}}
 
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 [[TIBC#Interpretation|interpretation of TIBC]]. Low transferrin likely indicates [[malnutrition]].
 
== Interactions ==
 
Transferrin has been shown to [[Protein-protein interaction|interact]] with [[insulin-like growth factor 2]]<ref name="pmid11749962">{{cite journal | vauthors = Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T | title = Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3 | journal = FEBS Letters | volume = 509 | issue = 3 | pages = 395–8 | date = Dec 2001 | pmid = 11749962 | doi = 10.1016/S0014-5793(01)03204-5 }}</ref> and [[IGFBP3]].<ref name="pmid11297622">{{cite journal | vauthors = Weinzimer SA, Gibson TB, Collett-Solberg PF, Khare A, Liu B, Cohen P | title = Transferrin is an insulin-like growth factor-binding protein-3 binding protein | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 4 | pages = 1806–13 | date = Apr 2001 | pmid = 11297622 | doi = 10.1210/jcem.86.4.7380 }}</ref> Transcriptional regulation of transferrin is upregulated by [[retinoic acid]].<ref name="pmid1315521">{{cite journal | vauthors = Hsu SL, Lin YF, Chou CK | title = Transcriptional regulation of transferrin and albumin genes by retinoic acid in human hepatoma cell line Hep3B | journal = The Biochemical Journal | volume = 283 | issue = 2 | pages = 611–5 | date = Apr 1992 | pmid = 1315521 | pmc = 1131079 | doi =  10.1042/bj2830611}}</ref>
 
==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]].<ref>{{cite journal | author = M Ching-Ming Chung | title = Structure and function of transferrin | journal = Biochemical Education | volume = 12 | issue = 4 | pages = 146–154 |date=October 1984 | doi = 10.1016/0307-4412(84)90118-3 | url = http://www.sciencedirect.com/science/article/pii/0307441284901183}}</ref>
 
== See also ==
* [[Beta-2 transferrin]]
* [[Beta-2 transferrin]]
* [[Transferrin receptor]]
* [[Transferrin receptor]]
* [[Total iron-binding capacity]]
* [[Transferrin saturation]]
* [[Ferritin]]


==External links==
== References ==
* {{MeshName|Transferrin}}
{{Reflist|33em}}


==References==
== Further reading ==
{{reflist|2}}
{{Refbegin}}
==Further reading==
* {{cite journal | vauthors = Hershberger CL, Larson JL, Arnold B, Rosteck PR, Williams P, DeHoff B, Dunn P, O'Neal KL, Riemen MW, Tice PA | title = A cloned gene for human transferrin | journal = Annals of the New York Academy of Sciences | volume = 646 | pages = 140–54 | date = Dec 1991 | pmid = 1809186 | doi = 10.1111/j.1749-6632.1991.tb18573.x }}
{{refbegin | 2}}
* {{cite journal | vauthors = Bowman BH, Yang FM, Adrian GS | title = Transferrin: evolution and genetic regulation of expression | journal = Advances in Genetics | volume = 25 | pages = 1–38 | year = 1989 | pmid = 3057819 | doi = 10.1016/S0065-2660(08)60457-5 | isbn = 9780120176250 | series = Advances in Genetics }}
{{PBB_Further_reading
* {{cite journal | vauthors = Parkkinen J, von Bonsdorff L, Ebeling F, Sahlstedt L | title = Function and therapeutic development of apotransferrin | journal = Vox Sanguinis | volume = 83 Suppl 1 | issue = Suppl 1 | pages = 321–6 | date = Aug 2002 | pmid = 12617162 | doi = 10.1111/j.1423-0410.2002.tb05327.x }}
| citations =
{{Refend}}
*{{cite journal | author=Hershberger CL, Larson JL, Arnold B, ''et al.'' |title=A cloned gene for human transferrin. |journal=Ann. N. Y. Acad. Sci. |volume=646 |issue=  |pages= 140-54 |year= 1992 |pmid= 1809186 |doi= }}
*{{cite journal | author=Bowman BH, Yang FM, Adrian GS |title=Transferrin: evolution and genetic regulation of expression. |journal=Adv. Genet. |volume=25 |issue=  |pages= 1-38 |year= 1989 |pmid= 3057819 |doi= }}
*{{cite journal | author=Parkkinen J, von Bonsdorff L, Ebeling F, Sahlstedt L |title=Function and therapeutic development of apotransferrin. |journal=Vox Sang. |volume=83 Suppl 1 |issue= |pages= 321-6 |year= 2003 |pmid= 12617162 |doi= }}
}}
{{refend}}


[[Category:Chemical pathology]]
== External links ==
* {{MeshName|Transferrin}}


{{Cell-biology-stub}}
{{PDB Gallery|geneid=7018}}
{{Iron-binding proteins}}
{{Iron-binding proteins}}
{{Beta globulins}}
{{Beta globulins}}
{{Acute phase proteins}}
{{Acute phase proteins}}
{{Iron metabolism}}


[[de:Transferrin]]
[[Category:Iron metabolism]]
[[nl:Transferrine]]
[[Category:Chemical pathology]]
[[pl:Transferyna]]
[[sv:Transferrin]]

Revision as of 11:12, 24 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Wikidata
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Transferrin
Identifiers
SymbolTransferrin
PfamPF00405
InterProIPR001156
PROSITEPDOC00182
SCOP1lcf
SUPERFAMILY1lcf
OPM superfamily161
OPM protein1lfc

Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron (Fe) in biological fluids.[1] Human transferrin is encoded by the TF gene.[2]

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)[3] but decreases progressively with decreasing pH below neutrality.

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

Transport mechanism

When a transferrin protein loaded with iron encounters a 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. The pH of the vesicle is reduced by hydrogen ion pumps (H+
 ATPases) to about 5.5, causing transferrin to release its iron ions. 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+
).

The gene coding for transferrin in humans is located in chromosome band 3q21.[2]

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

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.[4] 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. For the iron ion to bind, an anion is required, preferably carbonate (CO2−
3).[4]

Transferrin also has a transferrin iron-bound receptor; it is a disulfide-linked homodimer.[5] 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.[4]

Tissue distribution

The liver is the main site of transferrin synthesis but other tissues and organs, including the brain, also produce transferrin. The main role of transferrin is to deliver iron from absorption centers in the duodenum and white blood cell macrophages to all tissues. Transferrin plays a key role in areas where erythropoiesis and active cell division occur.[5] The receptor helps maintain iron homeostasis in the cells by controlling iron concentrations.[5]

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.[8]

Role in disease

An increased plasma transferrin level is often seen in patients suffering from 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[9] A decreased plasma transferrin can occur in iron overload diseases and protein malnutrition. An absence of transferrin results from a rare genetic disorder known as atransferrinemia, a condition characterized by anemia and hemosiderosis in the heart and liver that leads to heart failure and many other complications.

Transferrin and its receptor have been shown to diminish tumour cells when the receptor is used to attract antibodies.[10]

Other effects

Carbohydrate deficient transferrin increases in the blood with heavy ethanol consumption and can be monitored through laboratory testing.[11]

Transferrin is an acute phase protein and is therefore seen to decrease in inflammation, cancers, and certain diseases.[12]

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

File:Blood values sorted by mass and molar concentration.png
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 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[14] and IGFBP3.[15] Transcriptional regulation of transferrin is upregulated by retinoic acid.[16]

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.[17]

See also

References

  1. ↑ Crichton RR, Charloteaux-Wauters M (May 1987). "Iron transport and storage". European Journal of Biochemistry / FEBS. 164 (3): 485–506. doi:10.1111/j.1432-1033.1987.tb11155.x. PMID 3032619.
  2. ↑ 2.0 2.1 Yang F, Lum JB, McGill JR, Moore CM, Naylor SL, van Bragt PH, Baldwin WD, Bowman BH (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. doi:10.1073/pnas.81.9.2752. PMC 345148. PMID 6585826.
  3. ↑ Aisen P, Leibman A, Zweier J (Mar 1978). "Stoichiometric and site characteristics of the binding of iron to human transferrin". The Journal of Biological Chemistry. 253 (6): 1930–7. PMID 204636.
  4. ↑ 4.0 4.1 4.2 "Transferrin Structure". St. Edward's University. 2005-07-18. Archived from the original on 2012-12-11. Retrieved 2009-04-24.
  5. ↑ 5.0 5.1 5.2 Macedo MF, de Sousa M (Mar 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.
  6. ↑ 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.
  7. ↑ 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. doi:10.1073/pnas.0701574104. PMC 1871829. PMID 17420467.
  8. ↑ 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. PMID 10633294.
  9. ↑ Miller JL (2013). "Iron Deficiency Anemia: A Common and Curable Disease". Cold Spring Harbor perspectives in medicine. 3: a011866. doi:10.1101/cshperspect.a011866.
  10. ↑ Macedo, Maria F.; de Sousa, Maria (NaN). "Transferrin and the transferrin receptor: of magic bullets and other concerns". Inflammation & Allergy Drug Targets. 7: 41–52. doi:10.2174/187152808784165162. PMID 18473900. Check date values in: |date= (help)
  11. ↑ Sharpe PC (Nov 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.[permanent dead link]
  12. ↑ Jain S, Gautam V, Naseem S (Jan 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.
  13. ↑ "Normal Reference Range Table". Interactive Case Study Companion to Pathlogical 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.
  14. ↑ Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (Dec 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.
  15. ↑ Weinzimer SA, Gibson TB, Collett-Solberg PF, Khare A, Liu B, Cohen P (Apr 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.
  16. ↑ Hsu SL, Lin YF, Chou CK (Apr 1992). "Transcriptional regulation of transferrin and albumin genes by retinoic acid in human hepatoma cell line Hep3B". The Biochemical Journal. 283 (2): 611–5. doi:10.1042/bj2830611. PMC 1131079. PMID 1315521.
  17. ↑ M Ching-Ming Chung (October 1984). "Structure and function of transferrin". Biochemical Education. 12 (4): 146–154. doi:10.1016/0307-4412(84)90118-3.

Further reading

External links

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