TFRC (transferrin receptor (p90, CD71))

Identity

Other names	CD71
	OKT-9
	TFR1 (Transferrin receptor 1)
	TFR
	TRFR
	p90
	Mtvr-1 (mammary tumor virus receptor 1, in mice)
Hugo	TFRC
Location	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

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
Hugo	TFRC
GDB	TFRC
Entrez_Gene	TFRC  7037  transferrin receptor (p90, CD71)
	Cards
Atlas	TFRCID259ch3q29
GeneCards	TFRC
Ensembl	TFRC [Search_View]   ENSG00000072274 [Gene_View]
Genatlas	TFRC
GeneLynx	TFRC
eGenome	TFRC
euGene	7037
	Genomic and cartography
GoldenPath	TFRC  -  3q29   chr3:197260747-197293338 -  3q29   [Description]    (hg18-Mar_2006)
Ensembl	TFRC - 3q29 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	TFRC
	Gene and transcription
Genbank	AB209254 [ ENTREZ ]
Genbank	AK291723 [ ENTREZ ]
Genbank	AK309923 [ ENTREZ ]
Genbank	BC001188 [ ENTREZ ]
Genbank	BX537966 [ ENTREZ ]
RefSeq	NM_001128148 [ SRS ]    NM_001128148 [ ENTREZ ]
RefSeq	NM_003234 [ SRS ]    NM_003234 [ ENTREZ ]
RefSeq	AC_000046 [ SRS ]    AC_000046 [ ENTREZ ]
RefSeq	AC_000135 [ SRS ]    AC_000135 [ ENTREZ ]
RefSeq	NC_000003 [ SRS ]    NC_000003 [ ENTREZ ]
RefSeq	NT_029928 [ SRS ]    NT_029928 [ ENTREZ ]
RefSeq	NW_001838889 [ SRS ]    NW_001838889 [ ENTREZ ]
RefSeq	NW_921873 [ SRS ]    NW_921873 [ ENTREZ ]
AceView	TFRC AceView - NCBI
Unigene	Hs.529618 [ SRS ]    Hs.529618 [ NCBI ]     HS529618 [ spliceNest ]
Fast-db	15897 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P02786 [ SRS]    P02786 [ EXPASY ]     P02786 [ INTERPRO ]
Interpro	IPR003137 PA [ SRS ]    IPR003137 PA [ EBI ]
Interpro	IPR007365 Transferrin_rcpt-like_dimerise [ SRS ]    IPR007365 Transferrin_rcpt-like_dimerise [ EBI ]
CluSTr	P02786
Pfam	PF02225 PA [ SRS ]    PF02225 PA [ Sanger ]    pfam02225 [ NCBI-CDD ]
Pfam	PF04253 TFR_dimer [ SRS ]    PF04253 TFR_dimer [ Sanger ]    pfam04253 [ NCBI-CDD ]
Blocks	P02786
PDB	TFRC [ SRS ]    TFRC [ PdbSum ],   TFRC [ IMB ]   TFRC [ RSDB ]
HPRD	01812
	Protein Interaction databases
DIP	P02786
IntAct	P02786
	Polymorphism : SNP, mutations, diseases
OMIM	190010    [ map ]
GENECLINICS	190010
SNP	TFRC [dbSNP-NCBI]
SNP	NM_001128148 [SNP-NCI]
SNP	NM_003234 [SNP-NCI]
SNP	TFRC [GeneSNPs - Utah]  TFRC] [HGBASE - SRS]
HAPMAP	TFRC [HAPMAP]
COSMIC	TFRC [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	TFRC
	General knowledge
Family Browser	TFRC [UCSC Family Browser]
SOURCE	NM_001128148
SOURCE	NM_003234
SMD	Hs.529618
SAGE	Hs.529618
GO	receptor activity [Amigo]  receptor activity
GO	transferrin receptor activity [Amigo]  transferrin receptor activity
GO	extracellular region [Amigo]  extracellular region
GO	endosome [Amigo]  endosome
GO	plasma membrane [Amigo]  plasma membrane
GO	integral to plasma membrane [Amigo]  integral to plasma membrane
GO	cellular iron ion homeostasis [Amigo]  cellular iron ion homeostasis
GO	endocytosis [Amigo]  endocytosis
GO	cytoplasmic membrane-bounded vesicle [Amigo]  cytoplasmic membrane-bounded vesicle
GO	melanosome [Amigo]  melanosome
GO	perinuclear region of cytoplasm [Amigo]  perinuclear region of cytoplasm
BIOCARTA	The role of FYVE-finger proteins in vesicle transport    [Genes]
KEGG	Hematopoietic cell lineage
PubGene	TFRC
TreeFam	TFRC
CTD	7037 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	TFRC Related clones (RZPD - Berlin)
	PubMed
PubMed	121 Pubmed reference(s) in LocusLink

Bibliography

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PMID 11096344

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Contributor(s)

Written	04-2008	M 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 17:51:10 2008