Transferrin receptor 1

TFRC
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1CX8, 1DE4, 1SUV, 2NSU, 3KAS, 3S9L, 3S9M, 3S9N
Identifiers
Aliases	TFRC, CD71, T9, TFR, TFR1, TR, TRFR, p90, IMD46, transferrin receptor
External IDs	OMIM: 190010; MGI: 98822; HomoloGene: 2429; GeneCards: TFRC; OMA:TFRC - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	196,082,096 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	32,451,612 bp
RNA expression pattern
	Top expressed in
	endothelial cell; ; trabecular bone; ; tibia; ; germinal epithelium; ; visceral pleura; ; hair follicle; ; parietal pleura; ; periodontal fiber; ; mucosa of sigmoid colon; ; bone marrow;
	Top expressed in
	fetal liver hematopoietic progenitor cell; ; body of femur; ; habenula; ; stroma of bone marrow; ; tibiofemoral joint; ; temporal muscle; ; human fetus; ; vastus lateralis muscle; ; digastric muscle; ; ankle;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	protein homodimerization activity; virus receptor activity; transferrin receptor activity; identical protein binding; double-stranded RNA binding; RNA binding; protein binding;
Cellular component	extracellular vesicle; integral component of membrane; recycling endosome; HFE-transferrin receptor complex; endosome; blood microparticle; membrane; melanosome; plasma membrane; integral component of plasma membrane; extracellular region; cell surface; basolateral plasma membrane; perinuclear region of cytoplasm; clathrin-coated pit; extracellular exosome; external side of plasma membrane; extracellular space; clathrin-coated vesicle membrane; cytoplasmic vesicle; endosome membrane; early endosome;
Biological process	endocytosis; osteoclast differentiation; positive regulation of bone resorption; receptor-mediated endocytosis; regulation of cell population proliferation; regulation of cell growth; viral entry into host cell; viral process; cellular iron ion homeostasis; positive regulation of isotype switching; receptor internalization; transferrin transport; positive regulation of B cell proliferation; positive regulation of T cell proliferation; membrane organization; cellular response to leukemia inhibitory factor; iron ion transport;
	Sources:Amigo / QuickGO
Orthologs
	7037
	22042
	ENSG00000072274
	ENSMUSG00000022797
	P02786
	Q62351
	NM_001313965; NM_001313966; NM_001128148; NM_003234
	NM_011638; NM_001357298
	NP_001121620; NP_001300894; NP_001300895; NP_003225
	NP_035768; NP_001344227
	Wikidata
View/Edit Human	View/Edit Mouse

Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene.^[5]^[6] TfR1 is required for iron import from transferrin into cells by endocytosis.^[7]^[8]

Structure and function

TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis.^[9]

Clinical significance

TfR1 as a potential new target in cases of human leukemia & lymphoma. InatherYs, in Évry, France, developed a candidate drug, INA01 antibody (anti-CD71) that showed efficacy in pre-clinical studies in the therapy of two incurable orphan oncohematological diseases: the adult T cell leukemia (ATLL) caused by HTLV-1 and the Mantle cell lymphoma (MCL).^{[citation needed]}

TfR1 expressed on the endothelial cells of the blood-brain barrier (BBB) is used also in preclinical research to allow the delivery of large molecules including antibodies into the brain.^[10] Some of the TfR1 targeting antibodies have been shown to cross the blood-brain barrier, without interfering with the uptake of iron. Amongst those are the mouse anti rat-TfR antibody OX26^[11] and the rat anti mouse-TfR antibody 8D3.^[12] The affinity of the antibody-TfR interaction seems to be important determining the success of transcytotic transport over endothelial cells of the BBB. Monovalent TfR interaction favors BBB transport due to altered intracellular sorting pathways. Avidity effects of bivalent interactions redirecting transport to the lysosome.^[13] Also, reducing TfR binding affinity directly promote dissociation from the TfR which increase brain parenchymal exposure of the TfR binding antibody.^[14]

Interactions

TfR1 has been shown to interact with GABARAP^[15] and HFE.^[16]^[17]

Immunostain marker

CD71 is a robust immunohistochemistry marker for chorionic villi, especially in necrotic specimens. Among white blood cells and precursors, CD71 is expressed only by erythroid precursors within the normal hematopoietic marrow and spleen, in contrast to glycophorin that marks all types of red blood cells.^[18]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000072274 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022797 – 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.
^ Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M (July 1981). "Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin". Proceedings of the National Academy of Sciences of the United States of America. 78 (7): 4515–9. Bibcode:1981PNAS...78.4515S. doi:10.1073/pnas.78.7.4515. PMC 319822. PMID 6270680.
^ Rabin M, McClelland A, Kühn L, Ruddle FH (November 1985). "Regional localization of the human transferrin receptor gene to 3q26.2----qter". American Journal of Human Genetics. 37 (6): 1112–6. PMC 1684729. PMID 3002171.
^ Aisen P (November 2004). "Transferrin receptor 1". The International Journal of Biochemistry & Cell Biology. 36 (11): 2137–43. doi:10.1016/j.biocel.2004.02.007. PMID 15313461.
^ Moos T (November 2002). "Brain iron homeostasis". Danish Medical Bulletin. 49 (4): 279–301. PMID 12553165.
^ Speeckaert MM, Speeckaert R, Delanghe JR (December 2010). "Biological and clinical aspects of soluble transferrin receptor". Critical Reviews in Clinical Laboratory Sciences. 47 (5–6): 213–28. doi:10.3109/10408363.2010.550461. PMID 21391831. S2CID 25425279.
^ Johnsen KB, Burkhart A, Thomsen LB, Andresen TL, Moos T (October 2019). "Targeting the transferrin receptor for brain drug delivery" (PDF). Progress in Neurobiology. 181: 101665. doi:10.1016/j.pneurobio.2019.101665. PMID 31376426. S2CID 199405122.
^ Pardridge WM, Buciak JL, Friden PM (October 1991). "Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 66–70. PMID 1920136.
^ Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM (March 2000). "Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse". The Journal of Pharmacology and Experimental Therapeutics. 292 (3): 1048–52. PMID 10688622.
^ Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, et al. (January 2014). "Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle". Neuron. 81 (1): 49–60. doi:10.1016/j.neuron.2013.10.061. PMID 24411731.
^ Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. (May 2011). "Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target". Science Translational Medicine. 3 (84): 84ra44. doi:10.1126/scitranslmed.3002230. PMID 21613623. S2CID 34161824.
^ Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP" (PDF). FEBS Letters. 518 (1–3): 101–6. doi:10.1016/S0014-5793(02)02655-8. PMID 11997026. S2CID 29391940.
^ Feder JN, Penny DM, Irrinki A, Lee VK, Lebrón JA, Watson N, et al. (February 1998). "The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1472–7. Bibcode:1998PNAS...95.1472F. doi:10.1073/pnas.95.4.1472. PMC 19050. PMID 9465039.
^ West AP, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ (December 2000). "Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE". The Journal of Biological Chemistry. 275 (49): 38135–8. doi:10.1074/jbc.C000664200. PMID 11027676.
^ Morelli L, Luchini C (14 May 2021) [16 November 2020]. "CD71". Pathology Outlines.

External links

Overview of all the structural information available in the PDB for UniProt: P02786 (Human Transferrin receptor protein 1) at the PDBe-KB.

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000072274 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022797 – 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.

[pmid6270680-5] Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M (July 1981). "Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin". Proceedings of the National Academy of Sciences of the United States of America. 78 (7): 4515–9. Bibcode:1981PNAS...78.4515S. doi:10.1073/pnas.78.7.4515. PMC 319822. PMID 6270680.

[pmid3002171-6] Rabin M, McClelland A, Kühn L, Ruddle FH (November 1985). "Regional localization of the human transferrin receptor gene to 3q26.2----qter". American Journal of Human Genetics. 37 (6): 1112–6. PMC 1684729. PMID 3002171.

[pmid15313461-7] Aisen P (November 2004). "Transferrin receptor 1". The International Journal of Biochemistry & Cell Biology. 36 (11): 2137–43. doi:10.1016/j.biocel.2004.02.007. PMID 15313461.

[pmid12553165-8] Moos T (November 2002). "Brain iron homeostasis". Danish Medical Bulletin. 49 (4): 279–301. PMID 12553165.

[9] Speeckaert MM, Speeckaert R, Delanghe JR (December 2010). "Biological and clinical aspects of soluble transferrin receptor". Critical Reviews in Clinical Laboratory Sciences. 47 (5–6): 213–28. doi:10.3109/10408363.2010.550461. PMID 21391831. S2CID 25425279.

[10] Johnsen KB, Burkhart A, Thomsen LB, Andresen TL, Moos T (October 2019). "Targeting the transferrin receptor for brain drug delivery" (PDF). Progress in Neurobiology. 181: 101665. doi:10.1016/j.pneurobio.2019.101665. PMID 31376426. S2CID 199405122.

[11] Pardridge WM, Buciak JL, Friden PM (October 1991). "Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 66–70. PMID 1920136.

[12] Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM (March 2000). "Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse". The Journal of Pharmacology and Experimental Therapeutics. 292 (3): 1048–52. PMID 10688622.

[13] Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P, et al. (January 2014). "Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle". Neuron. 81 (1): 49–60. doi:10.1016/j.neuron.2013.10.061. PMID 24411731.

[14] Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. (May 2011). "Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target". Science Translational Medicine. 3 (84): 84ra44. doi:10.1126/scitranslmed.3002230. PMID 21613623. S2CID 34161824.

[pmid11997026-15] Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP" (PDF). FEBS Letters. 518 (1–3): 101–6. doi:10.1016/S0014-5793(02)02655-8. PMID 11997026. S2CID 29391940.

[pmid9465039-16] Feder JN, Penny DM, Irrinki A, Lee VK, Lebrón JA, Watson N, et al. (February 1998). "The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding". Proceedings of the National Academy of Sciences of the United States of America. 95 (4): 1472–7. Bibcode:1998PNAS...95.1472F. doi:10.1073/pnas.95.4.1472. PMC 19050. PMID 9465039.

[pmid11027676-17] West AP, Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ (December 2000). "Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE". The Journal of Biological Chemistry. 275 (49): 38135–8. doi:10.1074/jbc.C000664200. PMID 11027676.

[18] Morelli L, Luchini C (14 May 2021) [16 November 2020]. "CD71". Pathology Outlines.

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v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350