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Overview

Uniprot IDP02786
Protein NameTransferrin receptor protein 1
Gene NameTFRC
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
39 DNSHVEMKLAVDEEE

Function

Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738, PubMed:41772062). 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 hereditary 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). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity)

Protein Sequence

10 MMDQARSAFS 20 NLFGGEPLSY 30 TRFSLARQVD 40 GDNSHVEMKL 50 AVDEEENADN 60 NTKANVTKPK 70 RCSGSICYGT 80 IAVIVFFLIG 90 FMIGYLGYCK 100 GVEPKTECER 110 LAGTESPVRE 120 EPGEDFPAAR 130 RLYWDDLKRK 140 LSEKLDSTDF 150 TGTIKLLNEN 160 SYVPREAGSQ 170 KDENLALYVE 180 NQFREFKLSK 190 VWRDQHFVKI 200 QVKDSAQNSV 210 IIVDKNGRLV 220 YLVENPGGYV 230 AYSKAATVTG 240 KLVHANFGTK 250 KDFEDLYTPV 260 NGSIVIVRAG 270 KITFAEKVAN 280 AESLNAIGVL 290 IYMDQTKFPI 300 VNAELSFFGH 310 AHLGTGDPYT 320 PGFPSFNHTQ 330 FPPSRSSGLP 340 NIPVQTISRA 350 AAEKLFGNME 360 GDCPSDWKTD 370 STCRMVTSES 380 KNVKLTVSNV 390 LKEIKILNIF 400 GVIKGFVEPD 410 HYVVVGAQRD 420 AWGPGAAKSG 430 VGTALLLKLA 440 QMFSDMVLKD 450 GFQPSRSIIF 460 ASWSAGDFGS 470 VGATEWLEGY 480 LSSLHLKAFT 490 YINLDKAVLG 500 TSNFKVSASP 510 LLYTLIEKTM 520 QNVKHPVTGQ 530 FLYQDSNWAS 540 KVEKLTLDNA 550 AFPFLAYSGI 560 PAVSFCFCED 570 TDYPYLGTTM 580 DTYKELIERI 590 PELNKVARAA 600 AEVAGQFVIK 610 LTHDVELNLD 620 YERYNSQLLS 630 FVRDLNQYRA 640 DIKEMGLSLQ 650 WLYSARGDFF 660 RATSRLTTDF 670 GNAEKTDRFV 680 MKKLNDRVMR 690 VEYHFLSPYV 700 SPKESPFRHV 710 FWGSGSHTLP 720 ALLENLKLRK 730 QNNGAFNETL 740 FRNQLALATW 750 TIQGAANALS 760 GDVWDIDNEF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016323 basolateral plasma membrane
Cellular Component GO:0072562 blood microparticle
Cellular Component GO:0009986 cell surface
Cellular Component GO:0030669 clathrin-coated endocytic vesicle membrane
Cellular Component GO:0005905 clathrin-coated pit
Cellular Component GO:0031410 cytoplasmic vesicle
Cellular Component GO:0005769 early endosome
Cellular Component GO:0005768 endosome
Cellular Component GO:0010008 endosome membrane
Cellular Component GO:0009897 external side of plasma membrane
Cellular Component GO:0070062 extracellular exosome
Cellular Component GO:0005576 extracellular region
Cellular Component GO:0005615 extracellular space
Cellular Component GO:1903561 extracellular vesicle
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:1990712 HFE-transferrin receptor complex
Cellular Component GO:0005764 lysosome
Cellular Component GO:0042470 melanosome
Cellular Component GO:0016020 membrane
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0098944 postsynaptic recycling endosome membrane
Cellular Component GO:0055037 recycling endosome
Cellular Component GO:0055038 recycling endosome membrane
Molecular Function GO:0003725 double-stranded RNA binding
Molecular Function GO:0030544 Hsp70 protein binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0004998 transferrin receptor activity
Molecular Function GO:0001618 virus receptor activity
Biological Process GO:0006953 acute-phase response
Biological Process GO:0007166 cell surface receptor signaling pathway
Biological Process GO:0071466 cellular response to xenobiotic stimulus
Biological Process GO:0006879 intracellular iron ion homeostasis
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0006826 iron ion transport
Biological Process GO:0060586 multicellular organismal-level iron ion homeostasis
Biological Process GO:0043066 negative regulation of apoptotic process
Biological Process GO:0010637 negative regulation of mitochondrial fusion
Biological Process GO:0030316 osteoclast differentiation
Biological Process GO:0030890 positive regulation of B cell proliferation
Biological Process GO:0043123 positive regulation of canonical NF-kappaB signal transduction
Biological Process GO:0010628 positive regulation of gene expression
Biological Process GO:0045830 positive regulation of isotype switching
Biological Process GO:1900182 positive regulation of protein localization to nucleus
Biological Process GO:0031334 positive regulation of protein-containing complex assembly
Biological Process GO:0042102 positive regulation of T cell proliferation
Biological Process GO:0031623 receptor internalization
Biological Process GO:0006898 receptor-mediated endocytosis
Biological Process GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels
Biological Process GO:0046688 response to copper ion
Biological Process GO:0001666 response to hypoxia
Biological Process GO:0010039 response to iron ion
Biological Process GO:0010042 response to manganese ion
Biological Process GO:0007584 response to nutrient
Biological Process GO:0032526 response to retinoic acid
Biological Process GO:0033572 transferrin transport
Biological Process GO:0150104 transport across blood-brain barrier

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.