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Gene Review

TF  -  transferrin

Homo sapiens

Synonyms: Beta-1 metal-binding globulin, PRO1400, PRO1557, PRO2086, Serotransferrin, ...
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Disease relevance of TF


Psychiatry related information on TF


High impact information on TF

  • Although the role of transferrin in mammalian iron homeostasis has been well characterized, the study of genetic disorders of iron metabolism has revealed other, transferrin-independent, mechanisms by which cells can acquire iron [11].
  • Several cargos destined for degradation are preferentially targeted to the dynamic endosomes, whereas the recycling ligand transferrin is nonselectively delivered to all early endosomes and effectively enriched in the larger, static population [12].
  • Structure of the human transferrin receptor-transferrin complex [13].
  • We identified probands who presented to a clinic with signs or symptoms of hemochromatosis or who had elevated transferrin-saturation values [14].
  • This domain when overexpressed in COS7 fibroblasts is shown to inhibit transferrin uptake, whereas mutants in which interactions with its binding partners are abolished do not [15].

Chemical compound and disease context of TF

  • Two mechanisms of iron uptake from transferrin by melanoma cells. The effect of desferrioxamine and ferric ammonium citrate [16].
  • OBJECTIVE: The aim of the present work was to determine, in a cohort of men and women, whether ferritin and transferrin were associated with glucose metabolism and whether they were predictive of the onset of hyperglycemia (impaired fasting glycemia or type 2 diabetes) after 3 years of follow-up [17].
  • Iron(II)-glycine sulfate (Ferrosanol) and transferrin increased the cytotoxicity of free artesunate, artesunate microencapsulated in maltosyl-beta-cyclodextrin, and artemisinin toward CCRF-CEM leukemia and U373 astrocytoma cells 1.5- to 10.3-fold compared with that of artemisinins applied without iron [18].
  • Among the study subjects, hematocrit had direct univariate correlations with serum albumin concentration (r = 0.43; P = 0.02), transferrin saturation (r = 0.4; P = 0.03), and percent reduction of urea (r = 0.4; P = 0.02), but not with total CD4 count (r = -0.05; P = 0.8) or known duration of HIV infection (r = -0.11; P = 0.55) [19].
  • Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans [20].

Biological context of TF


Anatomical context of TF

  • During intracellular growth of the virulent Erdman M. tuberculosis strain in human monocyte-derived macrophages (MDM), M. tuberculosis acquisition of (59)Fe from transferrin (TF) provided extracellularly (exogenous source) was compared with acquisition when MDM were loaded with (59)Fe from TF prior to M. tuberculosis infection (endogenous sources) [26].
  • A dot binding assay involving the use of gonococcal total membranes derived from cells grown in iron-limited conditions demonstrated the presence of separate receptors for LF and TF [27].
  • Immunohistochemical analysis showed that the PDGF apoE2 x apoE(-)(/)(-) and the TF apoE2 x apoE(-)(/)(-) mice express human apoE2 within the neocortex in hippocampal neurons and glial cells, respectively [28].
  • K562 cells were not induced into a responsive state to LF, TF, or AIF by HuIFN gamma [29].
  • The influences of FCS, BSA, and TF in the presence of EP were studied on the proliferation of human bone marrow CFU-E and BFU-E [30].

Associations of TF with chemical compounds

  • M. tuberculosis infection decreased MDM-associated Fe relative to uninfected MDM as follows: TF (38.7%), citrate (21.1%), and LF (15.3%) [1].
  • The transferrins (TF) are a family of bilobal glycoproteins that tightly bind ferric iron [31].
  • Colony formation by cells preincubated in control medium plus indomethacin for 72 h was not decreased by treating cells with monoclonal anti-MHC class-II plus complement (C'), high specific activity tritiated thymidine (3HTdr), LF, TF, or AIF [32].
  • The TF C2 variant did not confer a risk for AD in Koreans [20].
  • Our data showed that the TF C1 homozygosity carriers had an increased risk of AD in subjects > or =75 years of age, showing that homozygosity for the TF C1 allele was associated with an approximately three-fold increased risk (OR=3.57, 95% CI, 1.24-10.27, P=0.014) [8].

Physical interactions of TF

  • Furthermore, at 4 degrees C, the added soluble complex of HFE/beta2m inhibited binding of transferrin to HeLa cell TfR in a concentration-dependent manner [33].
  • To investigate the underlying mechanism, we generated several TfR mutants with different binding affinities for transferrin [34].
  • Lactoferrin did not inhibit binding of transferrin, or vice versa [35].
  • Ferroxidase activity is assayed and characterized by coupling the oxidation with the binding of Fe(III) to transferrin [36].
  • Nuclear localization of exogenously added IGFBP-3 was rapid, occurring within 15 min, inhibited by co-incubation and extracellular sequestration with IGF-I, and dependent on the transferrin-binding C-terminal peptide region of IGFBP-3 [37].

Enzymatic interactions of TF

  • A single cut-off point of 55% for transferrin saturation and a cut-off point at the 90th percentile for the serum ferritin level were adequate for the detection of hemochromatosis if homozygosity was considered to be present when the results of one or both tests were positive [38].
  • Lastly, urea PAGE showed that hephaestin was able to catalyze formation of diferric transferrin from Fe(II) and apotransferrin [39].

Co-localisations of TF

  • Furthermore, we have shown that the ARF6-containing intracellular compartment partially colocalized with transferrin receptors and cellubrevin and morphologically resembled the recycling endocytic compartment previously described in CHO cells [40].
  • By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells [41].
  • HDL protein that was internalized by SR-BII largely co-localized with transferrin in the endosomal recycling compartment [42].
  • The beta(1)AR/GRK2 fusion protein internalizes via clathrin-coated pits and is found to co-localize with the endosome that contains transferrin [43].

Regulatory relationships of TF


Other interactions of TF

  • Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer [48].
  • Rare variants were observed in the C3, Tf, and Pi systems [49].
  • Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia [50].
  • We measured urinary hepcidin levels in 10 patients homozygous for TFR2 mutations, all with increased transferrin saturation [51].
  • In conclusion, Tf and other target genes identified may play a functional role in the downstream pathway of GADD153 [52].

Analytical, diagnostic and therapeutic context of TF

  • S1 nuclease analysis and immunoblotting showed that the PDGF-B apoE2 mice express apoE2 exclusively in the brain whereas the TF apoE2 mice express apoE2 in the liver and in the brain [28].
  • We failed to detect a significant difference in genotypic frequencies and allelic frequencies of the TF polymorphism between the AD group and control group (P>0.1 by Chi square test) [20].
  • By an isoelectric focusing analysis, we found that the patient and his father shared a variant TF protein with an abnormal isoelectric point [22].
  • RESULTS: There was a highly significant correlation between LCA-reactive species by CIAE and pyridyl-amino-fucosylated biantennary sugar chain by HPLC in both AAT and TF [53].
  • We quantified concentrations of CP and TF by immunoassay in AD (n = 17) and PD (n = 12) cerebrospinal fluid (CSF) to determine whether these proteins could serve as disease markers [54].


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