TFRC transferrin receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: TFRCprovided by HGNC
Official Full Name: transferrin receptorprovided by HGNC
Primary source: HGNC:HGNC:11763
See related: Ensembl:ENSG00000072274 MIM:190010; AllianceGenome:HGNC:11763
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: T9; TR; TFR; p90; CD71; TFR1; TRFR; IMD46
Summary: 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]
Expression: Broad expression in bone marrow (RPKM 101.5), placenta (RPKM 60.5) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q29

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (196049284..196082090, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (198738962..198802440, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (195776155..195808961, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

E3 ubiquitin ligase CHIP interacts with transferrin receptor 1 for degradation and promotes cell proliferation through inhibiting ferroptosis in hepatocellular carcinoma.
Title: E3 ubiquitin ligase CHIP interacts with transferrin receptor 1 for degradation and promotes cell proliferation through inhibiting ferroptosis in hepatocellular carcinoma.
TFR1-Mediated Iron Metabolism Orchestrates Tumor Ferroptosis and Immunity in Non-Small Cell Lung Cancer.
Title: TFR1-Mediated Iron Metabolism Orchestrates Tumor Ferroptosis and Immunity in Non-Small Cell Lung Cancer.
Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.
Title: Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.
Human transferrin receptor can mediate SARS-CoV-2 infection.
Title: Human transferrin receptor can mediate SARS-CoV-2 infection.
METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke.
Title: METTL3 regulates TFRC ubiquitination and ferroptosis through stabilizing NEDD4L mRNA to impact stroke.
Transferrin receptor levels and its rare variant are associated with human obesity.
Title: Transferrin receptor levels and its rare variant are associated with human obesity.
Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition.
Title: Dysregulation of iron homeostasis by TfR-1 renders EZH2 wild type diffuse large B-cell lymphoma resistance to EZH2 inhibition.
The hepatic niche leads to aggressive natural killer cell leukemia proliferation through the transferrin-transferrin receptor 1 axis.
Title: The hepatic niche leads to aggressive natural killer cell leukemia proliferation through the transferrin-transferrin receptor 1 axis.
H3K9 trimethylation dictates neuronal ferroptosis through repressing Tfr1.
Title: H3K9 trimethylation dictates neuronal ferroptosis through repressing Tfr1.
TfR1 gene expression as a potential biomarker for iron deficiency in heart failure.
Title: TfR1 gene expression as a potential biomarker for iron deficiency in heart failure.

Submit: New GeneRIF Correction See all GeneRIFs (257)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
TFRC-related combined immunodeficiency MedGen: C5568133 OMIM: 616740 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seventy-five genetic loci influencing the human red blood cell. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Treatment of CD4+ T lymphocytes with HIV-1 gp120 before anti-CD3 stimulation impedes cell cycle progression as measured by reduced CD71 expression	PubMed
	env	CD4+ T cells infected with CCR5-tropic HIV-1 have significantly higher levels of activation-marker expression (e.g. CD25, CD71 and HLA-DR) than CD4+ T lymphocytes infected with CXCR4-tropic HIV-1	PubMed
Envelope surface glycoprotein gp160, precursor	env	Immunoblot of sucrose fractions to lipid raft marker Flotillin-1 and non-lipid raft marker TfR shows that HIV-1 Gag and Env interact with both Flotillin-1 and TfR in cells	PubMed
Nef	nef	Both HIV-1 Nef and Vpu downregulate the cell surface expression of transferrin receptor (TFRC, TfR, p90, CD71)	PubMed
	nef	HIV-1 Nef modulates the trafficking of transferrin receptor (TfR), the prototypical recycling surface protein, with the dileucine motif (amino acids 164-5) in Nef being required for this alteration of TfR recycling	PubMed
	nef	Treatment of uninfected and acutely or chronically infected MT-4 and H9 T-cells with exogenous HIV-1 Nef downregulates the expression of CD71	PubMed
Pr55(Gag)	gag	Immunoblot of sucrose fractions to lipid raft marker Flotillin-1 and non-lipid raft marker TfR shows that HIV-1 Gag and Env interact with both Flotillin-1 and TfR in cells	PubMed
Tat	tat	Transferrin receptor protein (TFRC) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS	PubMed
Vif	vif	HIV-1 Vif interacts with TFRC	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of transferrin receptor 1 (TFR1) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
Vpu	vpu	Both HIV-1 Nef and Vpu downregulate the cell surface expression of transferrin receptor (TFRC, TfR, p90, CD71)	PubMed
	vpu	HIV-1 Vpu predominantly co-localizes to the detergent-soluble fractions with a non-raft protein TfR and partially partitions to the detergent-resistant membrane fractions with a raft protein flotillin 1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-77671 (e-PCR)
- UniSTS:3862

G22035 (e-PCR)
- UniSTS:21813

SHGC-58250 (e-PCR)
- UniSTS:47418

GDB:181229 (e-PCR)
- UniSTS:155197

D3S2868E (e-PCR)
- UniSTS:150876

SHGC-77676 (e-PCR)
- UniSTS:48489

STS-H53118 (e-PCR)
- UniSTS:78998

SHGC-77673 (e-PCR)
- UniSTS:19879

TFRC_3331.2 (e-PCR)
- UniSTS:468152

RH135817 (e-PCR)
- UniSTS:209635

D3S4248 (e-PCR)
- UniSTS:753

D3S4193 (e-PCR)
- UniSTS:62460

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Hsp70 protein binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	PubMed
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferrin receptor activity	IC Inferred by Curator more info	PubMed
enables transferrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables transferrin receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to xenobiotic stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular iron ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular iron ion homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in intracellular signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in iron ion transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in iron ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of mitochondrial fusion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in osteoclast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of B cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of bone resorption	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of isotype switching	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein-containing complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor internalization	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to copper ion	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to iron ion	IEA Inferred from Electronic Annotation more info
involved_in response to manganese ion	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	IEA Inferred from Electronic Annotation more info
involved_in response to retinoic acid	IEA Inferred from Electronic Annotation more info
involved_in symbiont entry into host cell	IEA Inferred from Electronic Annotation more info
involved_in transferrin transport	IC Inferred by Curator more info	PubMed
involved_in transferrin transport	IDA Inferred from Direct Assay more info	PubMed
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of HFE-transferrin receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in blood microparticle	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in clathrin-coated pit	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	HDA more info	PubMed
located_in extracellular vesicle	HDA more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in recycling endosome	IDA Inferred from Direct Assay more info	PubMed
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: transferrin receptor protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046395.1 RefSeqGene

Range

5072..37878

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001128148.3 → NP_001121620.1 transferrin receptor protein 1 isoform 1

See identical proteins and their annotated locations for NP_001121620.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

BC001188, BX537966, CF994006, X01060

Consensus CDS

CCDS3312.1

UniProtKB/Swiss-Prot

D3DXB0, P02786, Q1HE24, Q59G55, Q9UCN0, Q9UCU5, Q9UDF9, Q9UK21

UniProtKB/TrEMBL

A8K6Q8

Related

ENSP00000353224.4, ENST00000360110.9

Conserved Domains (3) summary

cd09848
Location:385 → 610

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

cd02128
Location:201 → 377

PA_TfR; PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 ...

pfam04253
Location:642 → 750

TFR_dimer; Transferrin receptor-like dimerization domain
NM_001313965.2 → NP_001300894.1 transferrin receptor protein 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate 5' exon and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AC024937, BC001188, BX537966

Consensus CDS

CCDS82891.1

UniProtKB/TrEMBL

A8K6Q8, G3V0E5

Related

ENSP00000390133.1, ENST00000420415.5

Conserved Domains (3) summary

cd09848
Location:304 → 529

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

cd02128
Location:120 → 296

PA_TfR; PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 ...

pfam04253
Location:561 → 669

TFR_dimer; Transferrin receptor-like dimerization domain
NM_001313966.2 → NP_001300895.1 transferrin receptor protein 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two alternate 5' exons and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AC024937, AK294758, BC001188

Consensus CDS

CCDS93444.1

UniProtKB/TrEMBL

A0A8V8TM46, B7Z2I6

Related

ENSP00000513650.1, ENST00000698285.1

Conserved Domains (3) summary

cd09848
Location:103 → 328

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

pfam04253
Location:360 → 468

TFR_dimer; Transferrin receptor-like dimerization domain

cl10459
Location:1 → 95

Peptidases_S8_S53; Peptidase domain in the S8 and S53 families
NM_003234.4 → NP_003225.2 transferrin receptor protein 1 isoform 1

See identical proteins and their annotated locations for NP_003225.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AK291723, BC001188, BX537966, X01060

Consensus CDS

CCDS3312.1

UniProtKB/Swiss-Prot

D3DXB0, P02786, Q1HE24, Q59G55, Q9UCN0, Q9UCU5, Q9UDF9, Q9UK21

UniProtKB/TrEMBL

A8K6Q8

Related

ENSP00000376197.3, ENST00000392396.7

Conserved Domains (3) summary

cd09848
Location:385 → 610

M28_TfR; M28 Zn-peptidase Transferrin Receptor family

cd02128
Location:201 → 377

PA_TfR; PA_TfR: Protease-associated domain containing proteins like transferrin receptor (TfR). This group contains various PA domain-containing proteins similar to human TfR1 and TfR2. TfR1 and TfR2 are type II membrane proteins, belonging to the peptidase M28 ...

pfam04253
Location:642 → 750

TFR_dimer; Transferrin receptor-like dimerization domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

196049284..196082090 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047448786.1 → XP_047304742.1 transferrin receptor protein 1 isoform X1

UniProtKB/TrEMBL

A0A8V8TM46

Related

ENSP00000513655.1, ENST00000698294.1

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

198738962..198802440 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054347662.1 → XP_054203637.1 transferrin receptor protein 1 isoform X2
XM_054347660.1 → XP_054203635.1 transferrin receptor protein 1 isoform X2
XM_054347663.1 → XP_054203638.1 transferrin receptor protein 1 isoform X2
XM_054347661.1 → XP_054203636.1 transferrin receptor protein 1 isoform X2
XM_054347664.1 → XP_054203639.1 transferrin receptor protein 1 isoform X1

UniProtKB/TrEMBL

A0A8V8TM46