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TFRC (transferrin receptor (p90, CD71))

Written2008-04M Tevfik Dorak
Genomic Immunoepidemiology Laboratory, HUMIGEN LLC, The Institute for Genetic Immunology, Hamilton, NJ 08690-3303, USA

(Note : for Links provided by Atlas : click)

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
Atlas_Id 259
Location 3q29  [Link to chromosome band 3q29]
Location_base_pair Starts at 195776155 and ends at 195809032 bp from pter ( according to hg19-Feb_2009)  [Mapping TFRC.png]
Fusion genes
(updated 2016)
ATP11B (3q26.33) / TFRC (3q29)BCL6 (3q27.3) / TFRC (3q29)TFRC (3q29) / BCL6 (3q27.3)
TFRC (3q29) / CPA3 (3q24)TFRC (3q29) / FN1 (2q35)TFRC (3q29) / TCTEX1D2 (3q29)
TFRC (3q29) / TFRC (3q29)

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

Note
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.
  

Bibliography

Transferrin receptor 1.
Aisen P.
Int J Biochem Cell Biol. 2004 Nov;36(11):2137-43.
PMID 15313461
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 

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 journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TFRCID259ch3q29.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  3q27 rearrangements (BCL6) in non Hodgkin lymphoma;t(3;Var)(q27;Var) in non Hodgkin lymphoma
t(3;3)(q27;q29) TFRC/BCL6

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 0 ]
  Lung: Translocations in Squamous Cell Carcinoma

External links

Nomenclature
HGNC (Hugo)TFRC   11763
Cards
AtlasTFRCID259ch3q29
Entrez_Gene (NCBI)TFRC  7037  transferrin receptor
AliasesCD71; IMD46; T9; TFR; 
TFR1; TR; TRFR; p90
GeneCards (Weizmann)TFRC
Ensembl hg19 (Hinxton)ENSG00000072274 [Gene_View]  chr3:195776155-195809032 [Contig_View]  TFRC [Vega]
Ensembl hg38 (Hinxton)ENSG00000072274 [Gene_View]  chr3:195776155-195809032 [Contig_View]  TFRC [Vega]
ICGC DataPortalENSG00000072274
TCGA cBioPortalTFRC
AceView (NCBI)TFRC
Genatlas (Paris)TFRC
WikiGenes7037
SOURCE (Princeton)TFRC
Genomic and cartography
GoldenPath hg19 (UCSC)TFRC  -     chr3:195776155-195809032 -  3q29   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TFRC  -     3q29   [Description]    (hg38-Dec_2013)
EnsemblTFRC - 3q29 [CytoView hg19]  TFRC - 3q29 [CytoView hg38]
Mapping of homologs : NCBITFRC [Mapview hg19]  TFRC [Mapview hg38]
OMIM190010   
Gene and transcription
Genbank (Entrez)AB209254 AK291723 AK294758 AK309923 BC001188
RefSeq transcript (Entrez)NM_001128148 NM_001313965 NM_001313966 NM_003234
RefSeq genomic (Entrez)NC_000003 NC_018914 NG_046395 NT_005612 NW_004929312
Consensus coding sequences : CCDS (NCBI)TFRC
Cluster EST : UnigeneHs.529618 [ NCBI ]
CGAP (NCI)Hs.529618
Alternative Splicing GalleryENSG00000072274
Gene ExpressionTFRC [ NCBI-GEO ]   TFRC [ EBI - ARRAY_EXPRESS ]   TFRC [ SEEK ]   TFRC [ MEM ]
Gene Expression Viewer (FireBrowse)TFRC [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7037
GTEX Portal (Tissue expression)TFRC
Protein : pattern, domain, 3D structure
UniProt/SwissProtP02786 (Uniprot)
NextProtP02786  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP02786
Splice isoforms : SwissVarP02786 (Swissvar)
PhosPhoSitePlusP02786
Domains : Interpro (EBI)PA_domain    Peptidase_M28    TfR    TFR-like_dimer_dom   
Domain families : Pfam (Sanger)PA (PF02225)    Peptidase_M28 (PF04389)    TFR_dimer (PF04253)   
Domain families : Pfam (NCBI)pfam02225    pfam04389    pfam04253   
DMDM Disease mutations7037
Blocks (Seattle)TFRC
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   
Structural Biology KnowledgeBase1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
SCOP (Structural Classification of Proteins)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
CATH (Classification of proteins structures)1CX8    1DE4    1SUV    2NSU    3KAS    3S9L    3S9M    3S9N   
SuperfamilyP02786
Human Protein AtlasENSG00000072274
Peptide AtlasP02786
HPRD01812
IPIIPI00022462   IPI00384980   IPI00924935   IPI00925162   IPI00925384   
Protein Interaction databases
DIP (DOE-UCLA)P02786
IntAct (EBI)P02786
FunCoupENSG00000072274
BioGRIDTFRC
STRING (EMBL)TFRC
ZODIACTFRC
Ontologies - Pathways
QuickGOP02786
Ontology : AmiGOregulation of cell growth  virus receptor activity  response to hypoxia  glycoprotein binding  double-stranded RNA binding  transferrin receptor activity  transferrin receptor activity  protein binding  extracellular region  extracellular space  mitochondrion  endosome  plasma membrane  integral component of plasma membrane  coated pit  cellular iron ion homeostasis  receptor-mediated endocytosis  acute-phase response  aging  response to nutrient  external side of plasma membrane  cell surface  response to iron ion  response to manganese ion  membrane  cytoplasmic, membrane-bounded vesicle  basolateral plasma membrane  osteoclast differentiation  Hsp70 protein binding  response to retinoic acid  transferrin transmembrane transporter activity  transferrin transport  transferrin transport  cellular response to drug  regulation of cell proliferation  melanosome  identical protein binding  protein homodimerization activity  intracellular membrane-bounded organelle  poly(A) RNA binding  positive regulation of bone resorption  response to copper ion  viral entry into host cell  perinuclear region of cytoplasm  chaperone binding  recycling endosome  recycling endosome membrane  extracellular exosome  blood microparticle  iron ion import  extracellular vesicle  HFE-transferrin receptor complex  
Ontology : EGO-EBIregulation of cell growth  virus receptor activity  response to hypoxia  glycoprotein binding  double-stranded RNA binding  transferrin receptor activity  transferrin receptor activity  protein binding  extracellular region  extracellular space  mitochondrion  endosome  plasma membrane  integral component of plasma membrane  coated pit  cellular iron ion homeostasis  receptor-mediated endocytosis  acute-phase response  aging  response to nutrient  external side of plasma membrane  cell surface  response to iron ion  response to manganese ion  membrane  cytoplasmic, membrane-bounded vesicle  basolateral plasma membrane  osteoclast differentiation  Hsp70 protein binding  response to retinoic acid  transferrin transmembrane transporter activity  transferrin transport  transferrin transport  cellular response to drug  regulation of cell proliferation  melanosome  identical protein binding  protein homodimerization activity  intracellular membrane-bounded organelle  poly(A) RNA binding  positive regulation of bone resorption  response to copper ion  viral entry into host cell  perinuclear region of cytoplasm  chaperone binding  recycling endosome  recycling endosome membrane  extracellular exosome  blood microparticle  iron ion import  extracellular vesicle  HFE-transferrin receptor complex  
Pathways : BIOCARTAThe role of FYVE-finger proteins in vesicle transport [Genes]   
Pathways : KEGGHIF-1 signaling pathway    Endocytosis    Phagosome    Hematopoietic cell lineage   
REACTOMEP02786 [protein]
REACTOME PathwaysR-HSA-432722 Golgi Associated Vesicle Biogenesis [pathway]
REACTOME PathwaysR-HSA-917977 Transferrin endocytosis and recycling [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkTFRC
Wikipedia pathwaysTFRC
Orthology - Evolution
OrthoDB7037
GeneTree (enSembl)ENSG00000072274
Phylogenetic Trees/Animal Genes : TreeFamTFRC
Homologs : HomoloGeneTFRC
Homology/Alignments : Family Browser (UCSC)TFRC
Gene fusions - Rearrangements
Fusion : MitelmanATP11B/TFRC [3q26.33/3q29]  [t(3;3)(q26;q29)]  
Fusion : MitelmanTFRC/BCL6 [3q29/3q27.3]  [t(3;3)(q27;q29)]  [t(3;3)(q29;q27)]  
Fusion: TCGAATP11B 3q26.33 TFRC 3q29 HNSC
Fusion: TCGATFRC 3q29 CPA3 3q24 LUSC
Fusion: TCGATFRC 3q29 TCTEX1D2 3q29 BLCA
Fusion : TICdbTFRC [3q29]  -  BCL6 [3q27.3]
Polymorphisms : SNP, variants
NCBI Variation ViewerTFRC [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TFRC
dbVarTFRC
ClinVarTFRC
1000_GenomesTFRC 
Exome Variant ServerTFRC
ExAC (Exome Aggregation Consortium)TFRC (select the gene name)
Genetic variants : HAPMAP7037
Genomic Variants (DGV)TFRC [DGVbeta]
Mutations
ICGC Data PortalTFRC 
TCGA Data PortalTFRC 
Broad Tumor PortalTFRC
OASIS PortalTFRC [ Somatic mutations - Copy number]
Cancer Gene: CensusTFRC 
Somatic Mutations in Cancer : COSMICTFRC 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TFRC
DgiDB (Drug Gene Interaction Database)TFRC
DoCM (Curated mutations)TFRC (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TFRC (select a term)
intoGenTFRC
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)3:195776155-195809032  ENSG00000072274
CONAN: Copy Number AnalysisTFRC 
Mutations and Diseases : HGMDTFRC
OMIM190010   
MedgenTFRC
Genetic Testing Registry TFRC
NextProtP02786 [Medical]
TSGene7037
GENETestsTFRC
Huge Navigator TFRC [HugePedia]
snp3D : Map Gene to Disease7037
BioCentury BCIQTFRC
ClinGenTFRC
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7037
Chemical/Pharm GKB GenePA36478
Clinical trialTFRC
Miscellaneous
canSAR (ICR)TFRC (select the gene name)
Probes
Litterature
PubMed292 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTFRC
EVEXTFRC
GoPubMedTFRC
iHOPTFRC
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Aug 10 18:43:21 CEST 2016

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