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FLASH GENE

Symbol

TFRC

contributors: mct/npt/pgu - updated : 10-09-2017

HGNC name	transferrin receptor (p90, CD71)
HGNC id	11763

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive intestine         Homo sapiens   liver       highly Homo sapiens   mouth       highly Nervous spinal cord         Reproductive male system prostate       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Homo sapiens Fetal Digestive enterocyte Digestive epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	TFRC-N-Terminal fragment that is subject to regulated intramembrane proteolysis
	a protease associated (PA) domain
	an M28 peptidase domain
	a transferrin receptor-like dimerization domain

conjugated

GlycoP , LipoP , PhosphoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	homolog to rattus Tfrc (76.5 pc)
	homolog to murine Tfrc (77.3 pc)

Homologene

FAMILY	peptidase M28 family
	M28B subfamily

CATEGORY

receptor , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic,vesicle
text	associated with HEF in crypt cells, type 2 membrane protein
	cytoplasmic membrane-bound vesicle
	single-pass type II membrane protein

basic FUNCTION	playing a necessary role for development of erythrocytes and the nervous system
	involved in the cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes
	required for c-Myc-mediated cellular proliferation and cell size control
	its inhibition decreases cellular proliferation and results in G1 arrest without affecting cell size, and alters expression of genes that regulate the cell cycle
	mitochondrial biogenesis orchestrated by PPRGC1B, coupled with iron uptake through TFRC and iron supply to mitochondrial respiratory proteins, is a fundamental pathway linked to osteoclast activation and bone metabolism
	is a mitochondrial regulator
	facilitates cellular iron uptake through receptor-mediated endocytosis of iron-loaded transferrin
	implicated in homeostatic maintenance of the intestinal epithelium, acting through a role that is independent of its iron-uptake function
	importance of TFRC in adaptive immunity
	important iron transporter regulating iron homeostasis that has long been used as a marker for clathrin mediated endocytosis
	function in iron transport
	transferrin-bound iron is known to be delivered to cells by TFRC after internalization via clathrin-mediated endocytosis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

endocytosis transport

text	iron homeostasis
	iron ion transport

PATHWAY

metabolism

signaling

a component

homodimer disulfide-linked

INTERACTION

DNA

RNA

small molecule

protein	binding one transferrin or HFE molecule per subunit
	binding to the HLA class II histocompatibility antigen, DR1
	interacting with SH3BP3
	critical downstream target of c-Myc
	interacting with WWC1 (although suppression of WWC1 and dynein perturbs early endosome-to-endocytic recycling compartment transport, TFRC sorting is maintained
	interacting with TF through a loop in the N-lobe of serum transferrin that is critical for binding to the transferrin receptor
	important receptor for FTH1
	critical role for RBSN in determining the fate of TFRC internalized by clathrin-mediated endocytosis
	new function for TFRC in the control of IKK and NFKB1
	SPPL2A, and mainly SPPL2B are responsible for the intramembrane proteolysis of TFRC-N-terminal fragment
	TFRC has an important role in SPHK1-mediated oncogenesis
	TXLNA interacts with SNX4 and plays a role in the recycling pathway of TFRC
	STEAP3, a metalloreductase expressed in erythroblasts, associates with TFRC and partially rescues transferrin uptake
	functions as a regulator to control AMPA receptor trafficking efficiency and synaptic plasticity
	role of EGFR in modulating cellular iron homeostasis through redistribution of TFRC, which is essential for cancer development and progression

cell & other

REGULATION

Other	regulated by cellular iron levels through binding of the iron regulatory proteins, IRP1 and IRP2, to iron-responsive elements in the 3 prime-UTR
	up-regulated upon mitogenic stimulation
	its levels are regulated by cellular iron levels

ASSOCIATED DISORDERS

corresponding disease(s)

IMD46

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function in hepatoma cells due to a combination of iron deficiency and chemical hypoxia tumoral     --over   highly expressed in glioblastomas and associated with shorter survival (

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	it can be reliably used as an independent erythroid marker for immunohistochemical analysis of the marrow
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative   drugs that increase TFRC palmitoylation, are possible therapeutic approaches in the treatment of NBIA and also in more common neurodegenerative disorders, including Parkinson disease, where brain iron accumulation is also reported blood hemoglobin   erythroid-progenitor-targeted gene therapy using bifunctional TFRC Ligand-Peptides in erythropoietic protoporphyria

ANIMAL & CELL MODELS

mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy