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a globulin in blood plasma that carries iron (同)beta_globulin, siderophilin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/26 20:30:55」(JST)

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Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron 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 (10²³ 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., to erythroid precursors in the bone marrow), it binds to it and, as a consequence, 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, transferrin, bound) is then transported through the endocytic cycle back to the cell surface, ready for another round of iron uptake. Each transferrin molecule has the ability to carry two iron ions in the ferric form (Fe3+
).

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

Transferrin bound to its receptor.^[6]
Transferrin receptor complex.^[7]

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 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.^[5] 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.

Most recently, transferrin and its receptor have been shown to diminish tumour cells when the receptor is used to attract antibodies.^[5]

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.^[9]

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.^[10] Laboratory test results should always be interpreted using the reference range provided by the laboratory that performed the test.

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.

Interactions

Transferrin has been shown to interact with insulin-like growth factor 2^[11] and IGFBP3.^[12] Transcriptional regulation of transferrin is upregulated by retinoic acid.^[13]

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.^[14]

References

^ Crichton RR, Charloteaux-Wauters M (1987). "Iron transport and storage". Eur. J. Biochem. 164 (3): 485–506. doi:10.1111/j.1432-1033.1987.tb11155.x. PMID 3032619.
^ ^a ^b 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.
^ Aisen P, Leibman A, Zweier J (March 1978). "Stoichiometric and site characteristics of the binding of iron to human transferrin" (PDF). J. Biol. Chem. 253 (6): 1930–7. PMID 204636.
^ ^a ^b ^c "Transferrin Structure". St. Edward's University. 2005-07-18. Retrieved 2009-04-24.
^ ^a ^b ^c ^d ^e 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.
^ PDB: 1suv ; Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (February 2004). "Structure of the human transferrin receptor-transferrin complex". Cell 116 (4): 565–76. doi:10.1016/S0092-8674(04)00130-8. PMID 14980223.
^ PDB: 2nsu ; Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC, Nelson CD, Bowman VD, Battisti AJ, Chipman PR, Parrish CR, Rossmann MG (April 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.
^ 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". J. Clin. Lab. Anal. 13 (6): 273–9. doi:10.1002/(SICI)1098-2825(1999)13:6<273::AID-JCLA4>3.0.CO;2-X. PMID 10633294.
^ 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.
^ "Normal Reference Range Table". Interactive Case Study Companion to Pathlogical Basis of Disease. The University of Texas Southwestern Medical Center at Dallas. 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 Lett. 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. PMID 11749962.
^ 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". J. Clin. Endocrinol. Metab. 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". Biochem. J. 283 (2): 611–5. PMC 1131079. PMID 1315521.
^ 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.

External links

Transferrin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 成人の鉄欠乏症および鉄欠乏性貧血の原因と診断 causes and diagnosis of iron deficiency and iron deficiency anemia in adults
2. 鉄のバランス調節 regulation of iron balance
3. 心不全を有する成人における貧血に対するアプローチ approach to anemia in adults with heart failure
4. 鉄過剰が疑われる患者に対するアプローチ approach to the patient with suspected iron overload
5. 慢性疾患／炎症時の貧血 anemia of chronic disease inflammation

English Journal

Binding between lead ions and the high-abundance serum proteins.

Guo M1, He L2, Strong PJ3, Wang H4.
Chemosphere.Chemosphere.2014 Oct;112:472-80. doi: 10.1016/j.chemosphere.2014.05.018. Epub 2014 Jun 5.
The interaction between three of the most abundant bovine serum proteins (serum albumin, transferrin and IgG) with Pb(2+) was investigated using electrochemistry. The data was used to construct a new theoretical model of Pb(2+) binding to the high-abundance serum proteins under non-ideal conditions.
PMID 25048942

Topical drug delivery to retinal pigment epithelium with microfluidizer produced small liposomes.

Lajunen T1, Hisazumi K2, Kanazawa T3, Okada H3, Seta Y3, Yliperttula M4, Urtti A5, Takashima Y6.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Oct 1;62:23-32. doi: 10.1016/j.ejps.2014.04.018. Epub 2014 May 5.
Drug delivery from topically instilled eye drops to the posterior segment of the eye has long been one of the greatest challenges of ocular drug development. We developed methods of liposome preparation utilizing a microfluidizer to achieve adjustable nanoparticle size (even less than 80nm) and high
PMID 24810393

An autopsy case of microencephaly, bizarre putaminal lesion, and cerebellar atrophy with heart and liver diseases.

Okoshi Y1, Hayashi M2, Kanda S3, Yamamoto T4.
Brain & development.Brain Dev.2014 Sep;36(8):707-10. doi: 10.1016/j.braindev.2013.11.010. Epub 2014 Feb 1.
We reported a 64-year-old autopsy case, showing a unique combination of disorders in visceral organs and brain. She had developmental delay, microencephaly, and facial dysmorphism. She developed sick sinus syndrome and liver cirrhosis. There were no abnormalities in laboratory tests for congenital m
PMID 24491944

Japanese Journal

筋萎縮性側索硬化症の神経病理－我々の研究を中心に－

岡本幸市,Okamoto Koichi
The Kitakanto medical journal = 北関東医学 64(2), 109-116, 2014-05-01
… At present, only three proteins (cystatin C, transferrin and peripherin) have been shown to be present in Bunina bodies. …
NAID 120005429863

Plasma Transferrin Concentration as a Nutritional Marker in Malnourished Dogs with Nutritional Treatment

NAKAJIMA Mayumi,OHNO Koichi,GOTO-KOSHINO Yuko [他]
The journal of veterinary medical science 76(4), 539-543, 2014-04
NAID 40020087998

クルクミン含有漢方生薬、鉄含有食品摂取により鉄代謝異常が修飾されたCronkhite-Canada 症候群の1例

三好直美,中村真一,菅野仁,齋藤登,齋藤洋,野村馨,MIYOSHI Naomi,NAKAMURA Shinichi,KANNO Hitoshi,SAITO Noboru,SAITO Hiroshi,NOMURA Kaoru
東京女子医科大学雑誌 83(6), 408-412, 2013-12-25
症例は66歳男性、倦怠感、色素沈着、爪甲分離などを主訴に当院総合診療科を受診。消化管内視鏡検査により上部、下部消化管にポリポーシスを認め、Cronkhite-Canada症候群(CCS)と診断した。受診時、Hb 15.6 g/dl、血清鉄248 μg/dl、総鉄結合能274 μg/dlであり、トランスフェリン鉄飽和率は90.5 %と高値を呈した。一方貯蔵鉄量を示す血清フェリチンは34 ng/mlと …
NAID 110009659605

Related Pictures

★リンクテーブル★

リンク元	「トランスフェリン」「TF」「Tf」
拡張検索	「lactotransferrin」「transferrin-binding protein B」「transferrin-binding protein」「hypotransferrinemia」

「トランスフェリン」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Transferrin
Identifiers
Symbol	Transferrin
Pfam	PF00405
InterPro	IPR001156
PROSITE	PDOC00182
SCOP	1lcf
SUPERFAMILY	1lcf
OPM superfamily	161
OPM protein	1lfc
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Transferrin
	PDB rendering based on 1a8e.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1A8E, 1A8F, 1B3E, 1BP5, 1BTJ, 1D3K, 1D4N, 1DTG, 1FQE, 1FQF, 1JQF, 1N7W, 1N7X, 1N84, 1OQG, 1OQH, 1RYO, 1SUV, 2HAU, 2HAV, 2O7U, 2O84, 3FGS, 3QYT, 3S9L, 3S9M, 3S9N, 3SKP, 3V83, 3V89, 3V8X, 3VE1, 4H0W, 4X1B, 4X1D
Identifiers
Symbols	TF ; PRO1557; PRO2086; TFQTL1
External IDs	OMIM: 190000 MGI: 98821 HomoloGene: 68153 ChEMBL: 4865 GeneCards: TF Gene
Gene ontology
Molecular function	• protein binding; • ferric iron binding; • ferric iron transmembrane transporter activity; • transferrin receptor binding;
Cellular component	• extracellular region; • extracellular space; • early endosome; • late endosome; • coated pit; • basal plasma membrane; • cell surface; • endosome membrane; • cytoplasmic membrane-bounded vesicle; • apical plasma membrane; • endocytic vesicle; • vesicle; • secretory granule lumen; • basal part of cell; • perinuclear region of cytoplasm; • recycling endosome; • extracellular exosome; • blood microparticle; • HFE-transferrin receptor complex;
Biological process	• retina homeostasis; • platelet degranulation; • cellular iron ion homeostasis; • actin filament organization; • activation of JUN kinase activity; • blood coagulation; • platelet activation; • osteoclast differentiation; • regulation of protein stability; • transferrin transport; • positive regulation of bone resorption; • positive regulation of transcription, DNA-templated; • transmembrane transport; • SMAD protein signal transduction; • ERK1 and ERK2 cascade; • positive regulation of cell motility;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;