Browse TFRC

Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cell membrane Single-pass type II membrane protein Melanosome Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. ; SUBCELLULAR LOCATION: Transferrin receptor protein 1, serum form: Secreted
Domain PF02225 PA domain
PF04389 Peptidase family M28
PF04253 Transferrin receptor-like dimerisation domain
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). ; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.

> Gene Ontology
 
Biological Process GO:0000018 regulation of DNA recombination
GO:0000041 transition metal ion transport
GO:0001894 tissue homeostasis
GO:0002200 somatic diversification of immune receptors
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response
GO:0002208 somatic diversification of immunoglobulins involved in immune response
GO:0002250 adaptive immune response
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002377 immunoglobulin production
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus
GO:0002573 myeloid leukocyte differentiation
GO:0002637 regulation of immunoglobulin production
GO:0002639 positive regulation of immunoglobulin production
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002712 regulation of B cell mediated immunity
GO:0002714 positive regulation of B cell mediated immunity
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002889 regulation of immunoglobulin mediated immune response
GO:0002891 positive regulation of immunoglobulin mediated immune response
GO:0006310 DNA recombination
GO:0006826 iron ion transport
GO:0006875 cellular metal ion homeostasis
GO:0006879 cellular iron ion homeostasis
GO:0006898 receptor-mediated endocytosis
GO:0007159 leukocyte cell-cell adhesion
GO:0015682 ferric iron transport
GO:0016064 immunoglobulin mediated immune response
GO:0016444 somatic cell DNA recombination
GO:0016445 somatic diversification of immunoglobulins
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0019058 viral life cycle
GO:0019724 B cell mediated immunity
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030099 myeloid cell differentiation
GO:0030260 entry into host cell
GO:0030316 osteoclast differentiation
GO:0030888 regulation of B cell proliferation
GO:0030890 positive regulation of B cell proliferation
GO:0031623 receptor internalization
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0033572 transferrin transport
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
GO:0035690 cellular response to drug
GO:0042098 T cell proliferation
GO:0042100 B cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042110 T cell activation
GO:0042113 B cell activation
GO:0042129 regulation of T cell proliferation
GO:0042493 response to drug
GO:0043112 receptor metabolic process
GO:0044409 entry into host
GO:0045124 regulation of bone resorption
GO:0045190 isotype switching
GO:0045191 regulation of isotype switching
GO:0045453 bone resorption
GO:0045780 positive regulation of bone resorption
GO:0045785 positive regulation of cell adhesion
GO:0045830 positive regulation of isotype switching
GO:0045911 positive regulation of DNA recombination
GO:0046651 lymphocyte proliferation
GO:0046718 viral entry into host cell
GO:0046849 bone remodeling
GO:0046850 regulation of bone remodeling
GO:0046852 positive regulation of bone remodeling
GO:0046916 cellular transition metal ion homeostasis
GO:0048771 tissue remodeling
GO:0048871 multicellular organismal homeostasis
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050863 regulation of T cell activation
GO:0050864 regulation of B cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050871 positive regulation of B cell activation
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051701 interaction with host
GO:0051806 entry into cell of other organism involved in symbiotic interaction
GO:0051828 entry into other organism involved in symbiotic interaction
GO:0055072 iron ion homeostasis
GO:0055076 transition metal ion homeostasis
GO:0060249 anatomical structure homeostasis
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071593 lymphocyte aggregation
GO:0072512 trivalent inorganic cation transport
GO:0097286 iron ion import
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
Molecular Function GO:0001618 virus receptor activity
GO:0001948 glycoprotein binding
GO:0003725 double-stranded RNA binding
GO:0004998 transferrin receptor activity
GO:0005381 iron ion transmembrane transporter activity
GO:0008320 protein transmembrane transporter activity
GO:0008565 protein transporter activity
GO:0015091 ferric iron transmembrane transporter activity
GO:0015399 primary active transmembrane transporter activity
GO:0015405 P-P-bond-hydrolysis-driven transmembrane transporter activity
GO:0015450 P-P-bond-hydrolysis-driven protein transmembrane transporter activity
GO:0022804 active transmembrane transporter activity
GO:0022884 macromolecule transmembrane transporter activity
GO:0033570 transferrin transmembrane transporter activity
GO:0038024 cargo receptor activity
GO:0046873 metal ion transmembrane transporter activity
GO:0046915 transition metal ion transmembrane transporter activity
GO:0072510 trivalent inorganic cation transmembrane transporter activity
Cellular Component GO:0005905 clathrin-coated pit
GO:0009897 external side of plasma membrane
GO:0016323 basolateral plasma membrane
GO:0042470 melanosome
GO:0043235 receptor complex
GO:0048770 pigment granule
GO:0055037 recycling endosome
GO:0072562 blood microparticle
GO:0098552 side of membrane
GO:0098589 membrane region
GO:0098802 plasma membrane receptor complex
GO:1990712 HFE-transferrin receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04066 HIF-1 signaling pathway
hsa04144 Endocytosis
hsa04145 Phagosome
hsa04640 Hematopoietic cell lineage
Reactome R-HSA-8856825: Cargo recognition for clathrin-mediated endocytosis
R-HSA-421837: Clathrin derived vesicle budding
R-HSA-8856828: Clathrin-mediated endocytosis
R-HSA-432722: Golgi Associated Vesicle Biogenesis
R-HSA-917937: Iron uptake and transport
R-HSA-199991: Membrane Trafficking
R-HSA-917977: Transferrin endocytosis and recycling
R-HSA-382551: Transmembrane transport of small molecules
R-HSA-5653656: Vesicle-mediated transport
R-HSA-199992: trans-Golgi Network Vesicle Budding
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between TFRC and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between TFRC and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
17898788Adult T-Cell Leukemia/LymphomaInhibit immunityA24 binds TfR-1 (K(d) 2.7 nM) and competes with transferrin for receptor binding. It blocks the proliferation of malignant cells (TfR-1(high)), such as HTLV-I-infected T cells but not of resting cells. A24 induces TfR-1 endocytosis in lysosomal compartments where the receptor is degraded leading to intracellular iron deprivation. In HTLV-I-infected cells, A24 targets and induces apoptosis of both chronic and acute ATLL forms, independent of antibody aggregation, antibody-dependent cellular cytotoxicity and/or complement addition.
20530676Hematopoietic and Lymphoid Cell NeoplasmInhibit immunityDevelopment of human single-chain antibodies to the transferrin receptor that effectively antagonize the growth of leukemias and lymphomas. The major route of iron uptake by cells occurs through transferrin receptor (TfR)-mediated endocytosis of diferric-charged plasma transferrin (holo-Tf). In support of this hypothesis, the anti-TfR scFvs identified were antagonists of TfR binding to holo-Tf, particularly two of the most potent antibodies, 3TF12 and 3GH7, which blocked the in vitro proliferation of a number of hematopoietic cancer cell lines. Together, our findings define a new class of fully human anti-TfR antibodies suitable for immunotherapy against tumors whose proliferation relies on high levels of TfR and iron uptake, such as acute lymphoid and myeloid leukemias.
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of TFRC in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.51 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of TFRC in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.210.629
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)651.5130.491
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.7510.673
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1660.676
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7350.755
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5540.856
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1020.826
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0520.98
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2590.904
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.4940.72
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4520.817
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3050.0123
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of TFRC in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TFRC. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TFRC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TFRC.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TFRC. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of TFRC expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between TFRC and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolTFRC
Nametransferrin receptor
Aliases CD71; TFR1; transferrin receptor (p90, CD71); TFR; TRFR; CD antigen CD71; Transferrin receptor protein 1
Chromosomal Location3q29
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting TFRC collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting TFRC.
ID Name Drug Type Targets #Targets
DB01592IronSmall MoleculeAHSP, CP, EGLN1, FEN1, FTH1, FXN, HBA1, HDAC8, NEIL1, NEIL2, POLB, ......13