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TFRC (transferrin receptor (p90, CD71))

Identity

Other namesCD71
OKT-9
TFR1 (Transferrin receptor 1)
TFR
TRFR
p90
Mtvr-1 (mammary tumor virus receptor 1, in mice)
HGNC (Hugo) TFRC
LocusID (NCBI) 7037
Location 3q29
Location_base_pair Starts at 195776155 and ends at 195809032 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Note History and Nomenclature: The TFRC gene was assigned to chromosome 3 in 1982. It was located in 3q22 - qter the following year. It precisely maps to 3q29. Transferrin receptor was first detected as the proliferation-associated receptor for transferrin on leukemia cells. Transferrin receptor 2 is a distinct protein belonging to transferrin receptor-like family and its gene TFR maps to chromosome 7q22.
Transcription 13 alternative splicing variants have been described. The full-length transcript contains 19 exons encoding 760 amino acids.
Pseudogene There is no known pseudogene derived from TFRC.

Protein

Description A plasma membrane transport glycoprotein composed of disulfide-linked polypeptide chains, each 84.8-kDa molecular weight. Belongs to the peptidase m28 family.
Expression Expressed in a wide range of cell types and tissues. Expression level is highest in lymphocytes, placenta and neoplastic cells.
Localisation TFRC is a cell surface membrane protein.
Function TFRC is primarily involved in iron homeostasis by regulating cellular iron uptake in interaction with the HFE protein. It is also crucial in iron transportation from mother to fetus.
Transferrin receptor is the main receptor for transferrin and allows transferrin-bound iron uptake by the cell. Its expression is regulated by cellular iron requirements. Conserved iron-response elements in the 3'-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory proteins 1 and 2. The hereditary hemochromatosis protein HFE competes for binding with transferrin for an overlapping binding site. It is also involved in materno-fetal iron transport via the placenta.

Mutations

Note There are no disease-causing mutations in the TFRC gene. However, there are missense coding region variants that may have functional effects. The only one with appreciable frequency (rs3817672) is in exon 4 and encodes S142G amino acid substitution. This polymorphism does not have a homogeneous global distribution. Its minor allele in Caucasians is the major allele in Asians and Africans. There is no nonsense mutation described in TFRC. TFRC is not involved in any known translocations. Tfrc knockout mice are not viable and die during embryonic development due to erythropoietic and neuronal development problems.
The short arm of chromosome 3 also harbors other iron-related genes: transferrin (3q22.1), lactotransferrin (3q21-q23), melanotransferrin (3q28-q29) and ceruloplasmin (3q23-q25). Trisomy of chromosome 3, gain of the whole 3q arm and gain of 3q27-qter have been noted in various malignancies including both solid tumors and hematopoietic ones.

Implicated in

Entity Cancer Susceptibility
Note Overexpression of TFRC in malignant cells mediates higher iron uptake required for cell division. Expression is activated by c-Myc.
No mutation or variation in TFRC causes cancer and TFRC is not involved in cancer-associated translocations.
TFRC variant S142G modifies the associations of HFE C282Y mutation in cancer susceptibility for hepatocellular carcinoma, breast cancer, leukemia, colorectal cancer and multiple myeloma. Biological plausibility of these associations has been supported by the successful use of monoclonal antibodies against transferrin receptor in cancer treatment in vitro and in vivo.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494 t1119q23p13ID1540

External links

Nomenclature
HGNC (Hugo)TFRC   11763
Cards
AtlasTFRCID259ch3q29
Entrez_Gene (NCBI)TFRC  7037  transferrin receptor
GeneCards (Weizmann)TFRC
Ensembl (Hinxton)ENSG00000072274 [Gene_View]  chr3:195776155-195809032 [Contig_View]  TFRC [Vega]
ICGC DataPortalENSG00000072274
cBioPortalTFRC
AceView (NCBI)TFRC
Genatlas (Paris)TFRC
WikiGenes7037
SOURCE (Princeton)NM_001128148 NM_003234
Genomic and cartography
GoldenPath (UCSC)TFRC  -  3q29   chr3:195776155-195809032 -  3q26.2-qter   [Description]    (hg19-Feb_2009)
EnsemblTFRC - 3q26.2-qter [CytoView]
Mapping of homologs : NCBITFRC [Mapview]
OMIM190010   
Gene and transcription
Genbank (Entrez)AB209254 AK291723 AK294758 AK309923 BC001188
RefSeq transcript (Entrez)NM_001128148 NM_003234
RefSeq genomic (Entrez)AC_000135 NC_000003 NC_018914 NT_029928 NW_001838889 NW_004929312
Consensus coding sequences : CCDS (NCBI)TFRC
Cluster EST : UnigeneHs.529618 [ NCBI ]
CGAP (NCI)Hs.529618
Alternative Splicing : Fast-db (Paris)GSHG0022352
Alternative Splicing GalleryENSG00000072274
Gene ExpressionTFRC [ NCBI-GEO ]     TFRC [ SEEK ]   TFRC [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP02786 (Uniprot)
NextProtP02786  [Medical]
With graphics : InterProP02786
Splice isoforms : SwissVarP02786 (Swissvar)
Domains : Interpro (EBI)Peptidase_M28 [organisation]   Protease-assoc_domain [organisation]   TFR-like_dimer_dom [organisation]  
Related proteins : CluSTrP02786
Domain families : Pfam (Sanger)PA (PF02225)    Peptidase_M28 (PF04389)    TFR_dimer (PF04253)   
Domain families : Pfam (NCBI)pfam02225    pfam04389    pfam04253   
DMDM Disease mutations7037
Blocks (Seattle)P02786
PDB (SRS)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
PDB (PDBSum)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
PDB (IMB)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
PDB (RSDB)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
Human Protein AtlasENSG00000072274 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP02786
HPRD01812
IPIIPI00022462   IPI00384980   IPI00924935   IPI00925162   IPI00925384   
Protein Interaction databases
DIP (DOE-UCLA)P02786
IntAct (EBI)P02786
FunCoupENSG00000072274
BioGRIDTFRC
InParanoidP02786
Interologous Interaction database P02786
IntegromeDBTFRC
STRING (EMBL)TFRC
Ontologies - Pathways
Ontology : AmiGOdouble-stranded RNA binding  transferrin receptor activity  protein binding  extracellular region  endosome  plasma membrane  integral to plasma membrane  coated pit  proteolysis  cellular iron ion homeostasis  cellular iron ion homeostasis  peptidase activity  external side of plasma membrane  membrane  cytoplasmic membrane-bounded vesicle  modulation by virus of host morphology or physiology  osteoclast differentiation  transferrin transport  melanosome  identical protein binding  positive regulation of bone resorption  perinuclear region of cytoplasm  transmembrane transport  extracellular vesicular exosome  
Ontology : EGO-EBIdouble-stranded RNA binding  transferrin receptor activity  protein binding  extracellular region  endosome  plasma membrane  integral to plasma membrane  coated pit  proteolysis  cellular iron ion homeostasis  cellular iron ion homeostasis  peptidase activity  external side of plasma membrane  membrane  cytoplasmic membrane-bounded vesicle  modulation by virus of host morphology or physiology  osteoclast differentiation  transferrin transport  melanosome  identical protein binding  positive regulation of bone resorption  perinuclear region of cytoplasm  transmembrane transport  extracellular vesicular exosome  
Pathways : BIOCARTAThe role of FYVE-finger proteins in vesicle transport [Genes]   
Pathways : KEGGHIF-1 signaling pathway    Endocytosis    Phagosome    Hematopoietic cell lineage   
Protein Interaction DatabaseTFRC
Wikipedia pathwaysTFRC
Gene fusion - rearrangments
Rearrangement : TICdbTFRC [3q29]  -  BCL6 [8p11.23]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TFRC
snp3D : Map Gene to Disease7037
SNP (GeneSNP Utah)TFRC
SNP : HGBaseTFRC
Genetic variants : HAPMAPTFRC
Exome VariantTFRC
1000_GenomesTFRC 
ICGC programENSG00000072274 
Cancer Gene: CensusTFRC 
Somatic Mutations in Cancer : COSMICTFRC 
CONAN: Copy Number AnalysisTFRC 
Mutations and Diseases : HGMDTFRC
Genomic VariantsTFRC  TFRC [DGVbeta]
dbVarTFRC
ClinVarTFRC
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM190010   
MedgenTFRC
GENETestsTFRC
Disease Genetic AssociationTFRC
Huge Navigator TFRC [HugePedia]  TFRC [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneTFRC
Homology/Alignments : Family Browser (UCSC)TFRC
Phylogenetic Trees/Animal Genes : TreeFamTFRC
Chemical/Protein Interactions : CTD7037
Chemical/Pharm GKB GenePA36478
Clinical trialTFRC
Cancer Resource (Charite)ENSG00000072274
Other databases
Probes
Litterature
PubMed245 Pubmed reference(s) in Entrez
CoreMineTFRC
iHOPTFRC

Bibliography

Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.
Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M.
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515-9.
PMID 6270680
 
Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin.
Trowbridge IS, Omary MB.
Proc Natl Acad Sci U S A. 1981 May;78(5):3039-43.
PMID 6265934
 
Human transferrin receptor: expression of the receptor is assigned to chromosome 3.
Enns CA, Suomalainen HA, Gebhardt JE, Schroder J, Sussman HH.
Proc Natl Acad Sci U S A. 1982 May;79(10):3241-5.
PMID 6285343
 
Expression of human transferrin receptor is controlled by a gene on chromosome 3: assignment using species specificity of a monoclonal antibody.
Goodfellow PN, Banting G, Sutherland R, Greaves M, Solomon E, Povey S.
Somatic Cell Genet. 1982 Mar;8(2):197-206.
PMID 9732749
 
Chromosome 3q (22-ter) encodes the human transferrin receptor.
Miller YE, Jones C, Scoggin C, Morse H, Seligman P.
Am J Hum Genet. 1983 Jul;35(4):573-83.
PMID 6309000
 
The human transferrin receptor gene: genomic organization, and the complete primary structure of the receptor deduced from a cDNA sequence.
McClelland A, Kuhn LC, Ruddle FH.
Cell. 1984 Dec;39(2 Pt 1):267-74.
PMID 6094009
 
Regional localization of the human transferrin receptor gene to 3q26.2----qter.
Rabin M, McClelland A, Kuhn L, Ruddle FH.
Am J Hum Genet. 1985 Nov;37(6):1112-6.
PMID 3002171
 
Role of transferrin, Fe, and transferrin receptors in myeloid leukemia cell growth. Studies with an antitransferrin receptor monoclonal antibody.
Taetle R, Rhyner K, Castagnola J, To D, Mendelsohn J.
J Clin Invest. 1985 Mar;75(3):1061-7.
PMID 2984253
 
Mechanisms of growth inhibition by anti-transferrin receptor monoclonal antibodies.
Taetle R, Castagnola J, Mendelsohn J.
Cancer Res. 1986 Apr;46(4 Pt 1):1759-63.
PMID 3004704
 
Structure and function of transferrin receptors and their relationship to cell growth.
Trowbridge IS, Shackelford DA.
Biochem Soc Symp. 1986;51:117-29.
PMID 3545211
 
Translocation (3;21) in Philadelphia positive chronic myeloid leukemia: high resolution chromosomal analysis and immunological study on five new cases.
Lafage-Pochitaloff-Huvale M, Sainty D, Adriaanssen HJ, Lopez M, Maraninchi D, Simonetti J, Mannoni P, Carcassonne Y, Hagemeijer A.
Leukemia. 1989 Aug;3(8):554-9.
PMID 2747289
 
Combinations of anti-transferrin receptor monoclonal antibodies inhibit human tumor cell growth in vitro and in vivo: evidence for synergistic antiproliferative effects.
White S, Taetle R, Seligman PA, Rutherford M, Trowbridge IS.
Cancer Res. 1990 Oct 1;50(19):6295-301.
PMID 2400993
 
The blockage of the human transferrin receptor by a monoclonal antibody, EA.3, induces growth inhibition in leukemia cell lines.
Valentini M, Gregorini A, Bartolucci M, Porcellini A, Papa S.
Eur J Histochem. 1994;38 Suppl 1:61-8.
PMID 8547712
 
NotI linking/jumping clones of human chromosome 3: mapping of the TFRC, RAB7 and HAUSP genes to regions rearranged in leukemia and deleted in solid tumors.
Kashuba VI, Gizatullin RZ, Protopopov AI, Allikmets R, Korolev S, Li J, Boldog F, Tory K, Zabarovska V, Marcsek Z, Sumegi J, Klein G, Zabarovsky ER, Kisselev L.
FEBS Lett. 1997 Dec 15;419(2-3):181-5.
PMID 9428630
 
Interaction between haemochromatosis and transferrin receptor genes in multiple myeloma.
Van Landeghem GF, Beckman LE, Wahlin A, Markevärn B, Beckman L.
Lancet. 1998 Oct 17;352(9136):1285-6.
PMID 9788468
 
Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders.
Beckman LE, Van Landeghem GF, Sikström C, Wahlin A, Markevärn B, Hallmans G, Lenner P, Athlin L, Stenling R, Beckman L.
Carcinogenesis. 1999 Jul;20(7):1231-3.
PMID 10383894
 
Transferrin receptor is necessary for development of erythrocytes and the nervous system.
Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC.
Nat Genet. 1999 Apr;21(4):396-9.
PMID 10192390
 
Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma.
Racz A, Brass N, Heckel D, Pahl S, Remberger K, Meese E.
Eur J Cancer. 1999 Apr;35(4):641-6.
PMID 10492640
 
Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma.
Beckman LE, Hagerstrand I, Stenling R, Van Landeghem GF, Beckman L.
Oncology. 2000 Nov;59(4):317-22.
PMID 11096344
 
Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus.
Ross SR, Schofield JJ, Farr CJ, Bucan M.
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12386-90. Epub 2002 Sep 6.
PMID 12218182
 
Cytogenetic and molecular delineation of a region of chromosome 3q commonly gained in marginal zone B-cell lymphoma.
Gazzo S, Baseggio L, Coignet L, Poncet C, Morel D, Coiffier B, Felman P, Berger F, Salles G, Callet-Bauchu E.
Haematologica. 2003 Jan;88(1):31-8.
PMID 12551824
 
Transferrin receptor 1.
Aisen P.
Int J Biochem Cell Biol. 2004 Nov;36(11):2137-43.
PMID 15313461
 
Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis.
O'Donnell KA, Yu D, Zeller KI, Kim JW, Racke F, Thomas-Tikhonenko A, Dang CV.
Mol Cell Biol. 2006 Mar;26(6):2373-86.
PMID 16508012
 
PIK3CA and TFRC located in 3q are new prognostic factors in esophageal squamous cell carcinoma.
Wada S, Noguchi T, Takeno S, Kawahara K.
Ann Surg Oncol. 2006 Jul;13(7):961-6. Epub 2006 May 16.
PMID 16788758
 
Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses.
Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D, Li W, Nagel J, Schmidt PJ, Nunberg JH, Andrews NC, Farzan M, Choe H.
Nature. 2007 Mar 1;446(7131):92-6. Epub 2007 Feb 7.
PMID 17287727
 
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Contributor(s)

Written04-2008M Tevfik Dorak
Genomic Immunoepidemiology Laboratory, HUMIGEN LLC, The Institute for Genetic Immunology, Hamilton, NJ 08690-3303, USA

Citation

This paper should be referenced as such :
Dorak, MT
TFRC (transferrin receptor (p90, CD71))
Atlas Genet Cytogenet Oncol Haematol. 2009;13(3):222-224.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/TFRCID259ch3q29.html

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indexed on : Fri Jul 11 16:40:35 CEST 2014

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