This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015] See more...

Aliases for TFRC Gene

Aliases for TFRC Gene

  • Transferrin Receptor 2 3 5
  • Transferrin Receptor Protein 1 3 4
  • P90 3 4
  • T9 3 4
  • TR 3 4
  • Transferrin Receptor (P90, CD71) 2
  • CD71 Antigen 4
  • IMD46 3
  • CD71 3
  • TFR1 3
  • TRFR 3
  • TfR1 4
  • Trfr 4
  • TFR 3
  • TfR 4

External Ids for TFRC Gene

Previous GeneCards Identifiers for TFRC Gene

  • GC03M191708
  • GC03M195991
  • GC03M197183
  • GC03M197102
  • GC03M197264
  • GC03M195754
  • GC03M193076

Summaries for TFRC Gene

Entrez Gene Summary for TFRC Gene

  • This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

GeneCards Summary for TFRC Gene

TFRC (Transferrin Receptor) is a Protein Coding gene. Diseases associated with TFRC include Immunodeficiency 46 and Iron Deficiency Anemia. Among its related pathways are Hematopoietic cell lineage and Clathrin derived vesicle budding. Gene Ontology (GO) annotations related to this gene include double-stranded RNA binding. An important paralog of this gene is TFR2.

UniProtKB/Swiss-Prot Summary for TFRC Gene

  • Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240).
  • (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.

Gene Wiki entry for TFRC Gene

Additional gene information for TFRC Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TFRC Gene

Genomics for TFRC Gene

GeneHancer (GH) Regulatory Elements for TFRC Gene

Promoters and enhancers for TFRC Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TFRC on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TFRC

Top Transcription factor binding sites by QIAGEN in the TFRC gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • Nkx2-5

Genomic Locations for TFRC Gene

Genomic Locations for TFRC Gene
chr3:196,027,183-196,082,161
(GRCh38/hg38)
Size:
54,979 bases
Orientation:
Minus strand
chr3:195,754,054-195,809,060
(GRCh37/hg19)
Size:
55,007 bases
Orientation:
Minus strand

Genomic View for TFRC Gene

Genes around TFRC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TFRC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TFRC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TFRC Gene

Proteins for TFRC Gene

  • Protein details for TFRC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P02786-TFR1_HUMAN
    Recommended name:
    Transferrin receptor protein 1
    Protein Accession:
    P02786
    Secondary Accessions:
    • D3DXB0
    • Q1HE24
    • Q59G55
    • Q9UCN0
    • Q9UCU5
    • Q9UDF9
    • Q9UK21

    Protein attributes for TFRC Gene

    Size:
    760 amino acids
    Molecular mass:
    84871 Da
    Quaternary structure:
    • Homodimer; disulfide-linked. Binds one transferrin or HFE molecule per subunit. Binds the HLA class II histocompatibility antigen, DR1. Interacts with SH3BP3. Interacts with STEAP3; facilitates TFRC endocytosis in erythroid precursor cells (PubMed:26642240).
    • (Microbial infection) Interacts with Guanarito, Junin and Machupo arenavirus glycoprotein complex (PubMed:17287727, PubMed:18268337).
    Miscellaneous:
    • Serum transferrin receptor (sTfR) is used as a means of detecting erythropoietin (EPO) misuse by athletes and as a diagnostic test for anemia resulting from a number of conditions including rheumatoid arthritis, pregnancy, irritable bowel syndrome and in HIV patients.
    • Canine and feline parvoviruses bind human and feline transferrin receptors and use these receptors to enter and infect cells.
    SequenceCaution:
    • Sequence=BAD92491.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TFRC Gene

neXtProt entry for TFRC Gene

Post-translational modifications for TFRC Gene

  • N- and O-glycosylated, phosphorylated and palmitoylated. The serum form is only glycosylated.
  • Proteolytically cleaved on Arg-100 to produce the soluble serum form (sTfR).
  • Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the major site of palmitoylation.
  • Glycosylation at Asn55, Thr104, Asn251, Asn317, and Asn727
  • Ubiquitination at Lys39, Lys224, Lys344, Lys358, and Lys720
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • TFR1_HUMAN (607)

Antibody Products

No data available for DME Specific Peptides for TFRC Gene

Domains & Families for TFRC Gene

Gene Families for TFRC Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • CD markers
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins
  • Transporters

Protein Domains for TFRC Gene

Blocks:
  • Protease-associated PA
  • Transferrin receptor-like dimerisation domain
  • Peptidase family M28
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TFRC Gene

GenScript: Design optimal peptide antigens:
  • p90 (TFR1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P02786

UniProtKB/Swiss-Prot:

TFR1_HUMAN :
  • Belongs to the peptidase M28 family. M28B subfamily.
Family:
  • Belongs to the peptidase M28 family. M28B subfamily.
genes like me logo Genes that share domains with TFRC: view

Function for TFRC Gene

Molecular function for TFRC Gene

UniProtKB/Swiss-Prot Function:
Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240).
UniProtKB/Swiss-Prot Function:
(Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.
UniProtKB/Swiss-Prot Induction:
Regulated by cellular iron levels through binding of the iron regulatory proteins, IRP1 and IRP2, to iron-responsive elements in the 3'-UTR. Up-regulated upon mitogenic stimulation.
GENATLAS Biochemistry:
transferrin receptor (p90),involved in the development of erythrocytes and the nervous system

Phenotypes From GWAS Catalog for TFRC Gene

Gene Ontology (GO) - Molecular Function for TFRC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001618 virus receptor activity IEA --
GO:0003723 RNA binding HDA 22658674
GO:0003725 double-stranded RNA binding IDA 21266579
GO:0004998 transferrin receptor activity IEA,NAS 1871153
GO:0005515 protein binding IPI 9465039
genes like me logo Genes that share ontologies with TFRC: view
genes like me logo Genes that share phenotypes with TFRC: view

Human Phenotype Ontology for TFRC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TFRC Gene

MGI Knock Outs for TFRC:

Animal Model Products

  • Taconic Biosciences Mouse Models for TFRC

CRISPR Products

miRNA for TFRC Gene

miRTarBase miRNAs that target TFRC

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TFRC

Clone Products

  • Addgene plasmids for TFRC

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TFRC Gene

Localization for TFRC Gene

Subcellular locations from UniProtKB/Swiss-Prot for TFRC Gene

Cell membrane; Single-pass type II membrane protein. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. {ECO:0000269 PubMed:17081065}.
[Transferrin receptor protein 1, serum form]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TFRC gene
Compartment Confidence
plasma membrane 5
extracellular 5
endosome 5
cytoskeleton 3
mitochondrion 3
nucleus 3
endoplasmic reticulum 3
cytosol 3
lysosome 3
golgi apparatus 3
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Endosomes (3)
  • Lysosomes (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TFRC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IDA,IEA 1871153
GO:0005615 extracellular space HDA 22664934
GO:0005623 cell IEA --
GO:0005768 endosome IDA,IEA 14612438
GO:0005769 early endosome IEA --
genes like me logo Genes that share ontologies with TFRC: view

Pathways & Interactions for TFRC Gene

genes like me logo Genes that share pathways with TFRC: view

SIGNOR curated interactions for TFRC Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for TFRC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001558 NOT regulation of cell growth IMP 7556058
GO:0006826 iron ion transport IDA 7556058
GO:0006879 cellular iron ion homeostasis IEA,NAS 1871153
GO:0006897 endocytosis IEA --
GO:0006898 receptor-mediated endocytosis IEA --
genes like me logo Genes that share ontologies with TFRC: view

Drugs & Compounds for TFRC Gene

(89) Drugs for TFRC Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Iron Approved, Experimental Pharma Target 1496
Ferric cation Approved Pharma Target, agonist 0
Ferrous ascorbate Approved Pharma Target 0
Ferrous fumarate Approved Pharma Target 92
Ferrous gluconate Approved Pharma Target 10

(57) Additional Compounds for TFRC Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TFRC: view

Transcripts for TFRC Gene

mRNA/cDNA for TFRC Gene

4 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TFRC

Clone Products

  • Addgene plasmids for TFRC

Alternative Splicing Database (ASD) splice patterns (SP) for TFRC Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b ^
SP1: - - - - - -
SP2: - - - - -
SP3: - - - - - - - -
SP4: - -
SP5: - -
SP6: - - -
SP7: - - -
SP8: -
SP9: -
SP10:
SP11:

ExUns: 18a · 18b · 18c ^ 19a · 19b · 19c ^ 20a · 20b · 20c ^ 21a · 21b · 21c
SP1: - -
SP2: - -
SP3: - -
SP4: - -
SP5:
SP6:
SP7:
SP8: - -
SP9:
SP10:
SP11:

Relevant External Links for TFRC Gene

GeneLoc Exon Structure for
TFRC

Expression for TFRC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TFRC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TFRC Gene

This gene is overexpressed in Placenta (27.7) and Fetal Liver (8.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TFRC Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TFRC

SOURCE GeneReport for Unigene cluster for TFRC Gene:

Hs.529618

Evidence on tissue expression from TISSUES for TFRC Gene

  • Nervous system(4.9)
  • Liver(4.8)
  • Bone marrow(4.7)
  • Eye(4.6)
  • Intestine(4)
  • Blood(3.6)
  • Kidney(3.2)
  • Lung(3.1)
  • Spleen(3)
  • Heart(2.9)
  • Skin(2.9)
  • Lymph node(2.6)
  • Muscle(2.3)
  • Pancreas(2.3)
  • Adrenal gland(2)
genes like me logo Genes that share expression patterns with TFRC: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TFRC Gene

Orthologs for TFRC Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TFRC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TFRC 31 30
  • 99.69 (n)
OneToOne
dog
(Canis familiaris)
Mammalia TFRC 31 30
  • 84.74 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TFRC 31 30
  • 83.84 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Tfrc 17 31 30
  • 81.82 (n)
rat
(Rattus norvegicus)
Mammalia Tfrc 30
  • 80.85 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia TFRC 31
  • 66 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 61 (a)
OneToMany
-- 31
  • 61 (a)
OneToMany
chicken
(Gallus gallus)
Aves TFRC 31 30
  • 61 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TFRC 31
  • 50 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC101734813 30
  • 58.21 (n)
Str.15779 30
zebrafish
(Danio rerio)
Actinopterygii tfr1a 31 30
  • 54.57 (n)
OneToMany
tfr1b 31 31
  • 39 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes VPS70 31
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 24 (a)
ManyToMany
Species where no ortholog for TFRC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TFRC Gene

ENSEMBL:
Gene Tree for TFRC (if available)
TreeFam:
Gene Tree for TFRC (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TFRC: view image

Paralogs for TFRC Gene

Paralogs for TFRC Gene

(2) SIMAP similar genes for TFRC Gene using alignment to 5 proteins:

  • TFR1_HUMAN
  • F5H6B1_HUMAN
  • F8WBE5_HUMAN
  • G3V0E5_HUMAN
  • H7C3V5_HUMAN
genes like me logo Genes that share paralogs with TFRC: view

Variants for TFRC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TFRC Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
708324 Likely Benign: not provided 196,064,408(-) C/T MISSENSE_VARIANT
708777 Benign: not provided 196,064,369(-) C/T MISSENSE_VARIANT
708778 Benign: not provided 196,068,122(-) A/G SYNONYMOUS_VARIANT,FIVE_PRIME_UTR_VARIANT
716449 Likely Benign: not provided 196,062,589(-) C/T SYNONYMOUS_VARIANT
717697 Benign: not provided 196,074,052(-) G/A SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for TFRC Gene

Structural Variations from Database of Genomic Variants (DGV) for TFRC Gene

Variant ID Type Subtype PubMed ID
esv2759213 CNV gain+loss 17122850
esv3424455 CNV insertion 20981092
esv3569219 CNV loss 25503493
nsv1002584 CNV gain 25217958
nsv1004940 CNV gain 25217958
nsv1006165 CNV gain 25217958
nsv1008512 CNV gain 25217958
nsv1010395 CNV gain 25217958
nsv10386 CNV loss 18304495
nsv428430 CNV gain+loss 18775914
nsv469518 CNV gain+loss 16826518
nsv471621 CNV gain+loss 15918152
nsv524410 CNV gain 19592680
nsv593069 CNV gain 21841781
nsv820015 CNV loss 19587683
nsv997797 CNV gain 25217958

Variation tolerance for TFRC Gene

Residual Variation Intolerance Score: 44.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.60; 78.13% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TFRC Gene

Human Gene Mutation Database (HGMD)
TFRC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TFRC

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TFRC Gene

Disorders for TFRC Gene

MalaCards: The human disease database

(68) MalaCards diseases for TFRC Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
immunodeficiency 46
  • imd46
iron deficiency anemia
  • iron-deficiency anemia
hemochromatosis, type 1
  • hfe1
gastric adenosquamous carcinoma
  • adenosquamous carcinoma of stomach
deficiency anemia
  • anemia
- elite association - COSMIC cancer census association via MalaCards
Search TFRC in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TFR1_HUMAN
  • Immunodeficiency 46 (IMD46) [MIM:616740]: An autosomal recessive primary immunodeficiency disorder characterized by early-onset chronic diarrhea, recurrent infections, hypo- or agammaglobulinemia, normal lymphocyte counts, intermittent neutropenia, and intermittent thrombocytopenia. {ECO:0000269 PubMed:26642240}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TFRC

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TFRC: view

No data available for Genatlas for TFRC Gene

Publications for TFRC Gene

  1. Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites. (PMID: 11800564) West AP … Bjorkman PJ (Journal of molecular biology 2001) 3 4 23 54
  2. Interaction between haemochromatosis and transferrin receptor genes in hepatocellular carcinoma. (PMID: 11096344) Beckman LE … Beckman L (Oncology 2000) 3 23 41 54
  3. Crystal structure of the ectodomain of human transferrin receptor. (PMID: 10531064) Lawrence CM … Harrison SC (Science (New York, N.Y.) 1999) 3 4 23 54
  4. Structural model of phospholipid-reconstituted human transferrin receptor derived by electron microscopy. (PMID: 9782058) Fuchs H … Gessner R (Structure (London, England : 1993) 1998) 3 4 23 54
  5. Functional analysis of human/chicken transferrin receptor chimeras indicates that the carboxy-terminal region is important for ligand binding. (PMID: 8631371) Buchegger F … Collawn JF (European journal of biochemistry 1996) 3 4 23 54

Products for TFRC Gene