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FLASH GENE
Symbol TFR2 contributors: mct/pgu - updated : 22-10-2011
HGNC name transferrin receptor 2
HGNC id 11762
Corresponding disease
HFE3 hemochromatosis, type 3
Location 7q22.1      Physical location : 100.218.038 - 100.239.173
Synonym symbol(s) HFE3, TFRC2, MGC126368
DNA
TYPE functioning gene
STRUCTURE 21.13 kb     18 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
RNA
TRANSCRIPTS type messenger
text alternatively spliced variants encoding different protein isoforms have been described (PMID: 10409623) (PMID: 9799793)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
18 - 2891 105 801 - 2010 20096706
  • TFR2alpha
  • type II membrane protein
  • binding with TF is about 50 times lower than that for the binding of TF to TFR1
    • 15 - 2471 - 630 - 2010 20096706
  • TFR2beta
  • lacks transmembrane portions and therefore is likely to be an intracellular protein
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiens
    Lymphoid/Immunelymph node   moderately
     thymus   moderately
    Reproductivefemale systemuteruscervix highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythroid Homo sapiens
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a protease associated (PA) domain
  • an M28 peptidase domain
  • a transferrin receptor-like dimerization domain
  • a mitochondrial targeting sequence that is sufficient to import the protein into these organelles
    • conjugated GlycoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to rattus Trfr2 (84.3 pc)
    homolog to murine Trfr2 (85.1 pc)
    intraspecies homolog to TFRC
    homolog to classical transferrin receptor 1 (TFR1)
    Homologene
    FAMILY
  • peptidase M28 family
  • M28B subfamily
    • CATEGORY receptor membrane , transport carrier
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • single-pass type II membrane protein
  • at the subcellular level, HFE2 and TFR2 were predominantly localized to the basolateral membrane domain of hepatocytes, which renders a functional interaction of these two proteins in iron homeostasis possible
    • basic FUNCTION
  • mediating cellular uptake of transferrin-bound iron in a non-iron dependent manner
  • is a modulator of hepcidin production in response to iron
  • have dual roles in iron metabolism, one is signalling, the other is iron transport
  • mediates transferrin-bound iron uptake by receptor-mediated endocytosis
  • TFR2/HFE complex is required for transcriptional regulation of hepcidin by holo-TF
  • both HFE and TFR2 are necessary for regulation of hepcidin (HAMP) expression
  • TFR2 and HFE are involved in holotransferrin-dependent signaling for the regulation of FURIN which involved Erk phosphorylation
  • may be involved in iron metabolism, hepatocyte function and erythrocyte differentiation
  • involved in iron metabolism by regulating hepcidin production in liver cells
  • EPO and TFR2 are involved in production of GDF15 by erythroid cells
  • exhibits a non hepatic function as a component of the EPOR complex and is required for efficient erythropoiesis
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text
  • iron ion homeostasis
  • iron ion transport
    • PATHWAY
    metabolism
    signaling
  • TF/TFR2 -mediated iron transport pathway in mitochondria of substantia nigra dopamine neurons, disrupted in Parkinson disease, and leading to iron accumulation
    • a component
  • component of the EPOR complex
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with HFE (HFE influences the functional properties of TFR2, suggesting a model in which the interaction of these proteins might influence signal transduction to hepcidin)
  • TFR2 associates with EPOR in the endoplasmic reticulum and is required for the efficient transport of this receptor to the cell surface
    • cell & other
    REGULATION
    Other negatively modulated by the hemochromatosis protein HFE
    its levels are regulated by transferrin saturation
    ASSOCIATED DISORDERS
    corresponding disease(s) HFE3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly expressed in colon cancer, preferentially associated with mucinous tumors
    Susceptibility to serum levels of iron variation
    Variant & Polymorphism other association of a common variant in the type-2 transferrin receptor (TFR2) gene with iron levels
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • iron overload due to deletion of Tfr2 in mice is more severe than that due to Hfe, and loss of both molecules results in pronounced iron overload