Atlas of Genetics and Cytogenetics in Oncology and Haematology

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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
Location 3q29
Location_base_pair Starts at 195776156 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.
  

External links

Nomenclature
HGNC (Hugo)TFRC   11763
Entrez_Gene (NCBI)TFRC  7037  transferrin receptor (p90, CD71)
Cards
AtlasTFRCID259ch3q29
GeneCards (Weizmann)TFRC
Ensembl (Hinxton)ENSG00000072274 [Gene_View]  TFRC [Vega]
AceView (NCBI)TFRC
Genatlas (Paris)TFRC
euGene (Indiana)7037
SOURCE (Stanford)NM_001128148 NM_003234
Gene Expression (Array Express) ENSG00000072274
Genomic and cartography
GoldenPath (UCSC)TFRC  -  3q29   chr3:195776156-195809032 -  3q29   [Description]    (hg19-Feb_2009)
EnsemblTFRC - 3q29 [CytoView]
Mapping of homologs : NCBITFRC [Mapview]
OMIM190010   
Gene and transcription
Gene : Genbank (Entrez)AB209254 AK291723 AK294758 AK309923 BC001188
Reference sequence (RefSeq transcript) :SRSNM_001128148 NM_003234
Reference transcript : EntrezNM_001128148 NM_003234
RefSeq genomic : SRSAC_000046 AC_000135 NC_000003 NT_029928 NW_001838889 NW_921873
RefSeq genomic : EntrezAC_000046 AC_000135 NC_000003 NT_029928 NW_001838889 NW_921873
Consensus coding sequences : CCDS NCBITFRC
Cluster EST : UnigeneHs.529618 [ SRS ] Hs.529618 [ NCBI ]
Alternative Splicing : Fast-db (Paris)15897
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtP02786 (SRS) P02786 (Expasy) P02786 (Uniprot)
With graphics : InterProP02786
Splice isoforms : VarSplice FASTAP02786(VarSplice FASTA)
Domains : Interpro (SRS)PA    Peptidase_M28    Transferrin_rcpt-like_dimerise   
Domains : Interpro (EBI)PA    Peptidase_M28    Transferrin_rcpt-like_dimerise   
Related proteins : CluSTrP02786
Domain families : Pfam SRSPA (PF02225)    Peptidase_M28 (PF04389)    TFR_dimer (PF04253)   
Domain families : Pfam SangerPA (PF02225)    Peptidase_M28 (PF04389)    TFR_dimer (PF04253)   
Domain families : Pfam NCBIpfam02225    pfam04389    pfam04253   
Blocks (Seattle)P02786
Crystal structure of protein : PDB SRS1CX8    1DE4    1SUV    2NSU    3KAS   
Crystal structure of protein : PDBSum1CX8    1DE4    1SUV    2NSU    3KAS   
Crystal structure of protein : IMB1CX8    1DE4    1SUV    2NSU    3KAS   
Crystal structure of protein : PDB RSDB1CX8    1DE4    1SUV    2NSU    3KAS   
Human Protein AtlasENSG00000072274
HPRD01812
Protein Interaction databases
DIP (DOE-UCLA)P02786
IntAct (EBI)P02786
FunCoupENSG00000072274
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITFRC
SNP : GeneSNP UtahTFRC
SNP : HGBaseTFRC
Genetic variants : HAPMAPTFRC
Cancer Gene: CensusTFRC 
Somatic Mutations in Cancer : COSMICTFRC 
Translocation Breakpoints in Cancer : TICdbTFRC 
Mutations and Diseases : HGMDTFRC
Hereditary diseases : OMIM190010   
Hereditary diseases : GENETests190010   
Diseases : Genetic AssociationTFRC
General knowledge
Homologs : HomoloGeneTFRC
Homology/Alignments : Family Browser UCSCTFRC
Phylogenetic Trees/Animal Genes : TreeFamTFRC
Chemical/Protein Interactions : CTD7037
Keywords Ontology : AmiGOresponse to hypoxia  receptor activity  transferrin receptor activity  extracellular region  mitochondrion  endosome  plasma membrane  integral to plasma membrane  coated pit  proteolysis  cellular iron ion homeostasis  endocytosis  acute-phase response  aging  response to nutrient  peptidase activity  response to organic substance  response to inorganic substance  response to iron ion  response to manganese ion  membrane  cytoplasmic membrane-bounded vesicle  response to retinoic acid  melanosome  interspecies interaction between organisms  response to copper ion  perinuclear region of cytoplasm  
Keywords Ontology : EGO-EBIresponse to hypoxia  receptor activity  transferrin receptor activity  extracellular region  mitochondrion  endosome  plasma membrane  integral to plasma membrane  coated pit  proteolysis  cellular iron ion homeostasis  endocytosis  acute-phase response  aging  response to nutrient  peptidase activity  response to organic substance  response to inorganic substance  response to iron ion  response to manganese ion  membrane  cytoplasmic membrane-bounded vesicle  response to retinoic acid  melanosome  interspecies interaction between organisms  response to copper ion  perinuclear region of cytoplasm  
Pathways : BIOCARTAThe role of FYVE-finger proteins in vesicle transport [Genes]   
Pathways : KEGGHematopoietic cell lineage
Other databases
Probes
Probes : ImagenesTFRC Related clones (RZPD - Berlin)
Literature
PubMed160 Pubmed reference(s) in Entrez
PubGeneTFRC

Bibliography

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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. April 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/TFRCID259ch3q29.html

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indexed on : Thu Jul 15 14:41:58 CEST 2010
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