| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.91173565 |
| These results establish a molecular link between HFE and a key protein involved in iron transport , the TfR , and raise the possibility that alterations in this regulatory mechanism may play a role in the pathogenesis of hereditary hemochromatosis . . 0.91173565^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.56642451 |
| We analyzed the cDNA sequences of transferrin receptor ( TFR ) , which was recently shown to interact with HFE , in twenty one hereditary hemochromatosis patients including sixteen individuals who did not carry a Cys 282 > Tyr mutation . 0.56642451^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.9145446 |
| Previous studies demonstrated that HFE and Fe Tf can bind simultaneously to TfR to form a ternary complex , and that membrane bound or soluble HFE binding to cell surface TfR results in a reduction in the affinity of TfR for Fe Tf . 0.9145446^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.75937526 |
| The structures of TfR alone and complexed with HFE differ in their domain arrangement and dimer interfaces , providing a mechanism for communicating binding events between TfR chains . 0.75937526^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.66555231 |
| Whether the interaction between HFE and TfR explains the pathogenesis of HH is not so clear . . 0.66555231^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.63761635 |
| Both techniques indicate that a 2 : 2 TfR / HFE complex can form at submicromolar concentrations in solution , consistent with the hypothesis that HFE competes for Tf binding to TfR by blocking the Tf binding site rather than by exerting an allosteric effect . 0.63761635^^^ In order to more fully characterize the interaction between HFE and TfR , we determined the binding stoichiometry using equilibrium gel filtration and analytical ultracentrifugation . 0.62917917^^^ The findings that both HFE and Tf form 2 : 2 complexes with TfR and that mutations at the HFE binding site affect Tf binding support a model in which HFE and Tf compete for overlapping binding sites on TfR . . 0.53125275^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.85738743 |
| The interaction between TfR and HFE LAMP was confirmed by immunoprecipitation , in addition to immunofluorescence studies . 0.85738743^^^ This implies that the interaction between HFE and TfR in endosomes targets the TfR to lysosomal compartments . 0.69337493^^^ HFE , the protein mutated in hereditary haemochromatosis type 1 , is known to interact with the transferrin receptor ( TfR ) on the cell surface and during endocytosis [ Gross , Irrinki , Feder and Enns ( 1998 ) J . 0.57233565^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.88441421 |
| These results indicate that the association of HFE with TfR is not essential for its ability to lower intracellular iron stores . 0.88441421^^^ The results indicate that HFE can lower intracellular iron levels independently of its interaction with the TfR . . 0.54860446^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.83332472 |
| This apparent affinity reduction could result from direct competition between HFE and Fe Tf for their overlapping binding sites on each TfR polypeptide chain , from negative cooperativity , or from a combination of both . 0.83332472^^^ HFE and Fe Tf can bind simultaneously to TfR to form a ternary complex , but HFE binding to TfR lowers the apparent affinity of the Fe Tf / TfR interaction . 0.62617272^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.61114294 |
| These data indicate that HFE can regulate intracellular iron storage independently of its interaction with TfR 1 . 0.61114294^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.59326398 |
| The hemochromatosis gene ( HFE ) produces a protein that interacts with TfR ; and we hypothesized that tumor cells would selectively mutate HFE to improve their iron uptake and thus provide themselves a growth advantage over non tumor cells . 0.59326398^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| TfR 2 is capable of Tf mediated iron uptake and mutations in this gene result in a rare form of hereditary hemochromatosis unrelated to the hereditary hemochromatosis protein , HFE . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE binds to transferrin receptor ( TfR ) and reduces its affinity for iron loaded transferrin , implicating HFE in iron metabolism . ^^^ We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface , but not at the acidic pH of intracellular vesicles . ^^^ TfR : HFE stoichiometry ( 2 : 1 ) differs from TfR : transferrin stoichiometry ( 2 : 2 ) , implying a different mode of binding for HFE and transferrin to TfR , consistent with our demonstration that HFE , transferrin , and TfR form a ternary complex . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The recent association of HFE gene with transferrin receptor ( TfR ) in trophoblast cells opens new possibilities on its role in cellular iron uptake . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| In placenta , the HFE protein colocalizes with and forms a stable association with the transferrin receptor ( TfR ) , providing a link between the HFE protein and iron transport . ^^^ In the present study , we examined the relationship of the HFE protein to the TfR in enterocytes of the human duodenum and measured the uptake of transferrin bound iron and ionic iron by isolated crypt and villus enterocytes . ^^^ Immunocytochemistry showed that the HFE protein and TfR both are expressed in the crypt enterocytes . ^^^ Western blots showed that , as was the case in human placenta , the HFE protein in crypt enterocytes is physically associated with the TfR and with beta 2 microglobulin . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Recent demonstration of an association between transferrin receptor ( TfR ) and HFE , a major histocompatibility complex class 1 like molecule that has been implicated to play a role in hereditary hemochromatosis , further strengthens the notion that HFE is involved in iron metabolism . ^^^ Herein we show that TfR is required for and controls the assembly and the intracellular transport and surface expression of HFE . ^^^ Because surface expressed HFE and TfR remain firmly associated physically , only the fraction of TfR that is associated with HFE during biosynthesis is affected functionally . ^^^ Moreover , we show that HFE binding reduces the number of functional transferrin binding sites and impairs TfR internalization , thus reducing the uptake of transferrin bound iron . ^^^ Thus , iron homeostasis is indirectly regulated by HFE , a negative modulator of TfR . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE binds tightly to transferrin receptor ( TfR ) , the receptor that mediates uptake of iron loaded transferrin . ^^^ The binding affinities for TfR of HFE mutants , designed using the HFE crystal structure , were measured using biosensor assays . ^^^ The results allow localization of the TfR binding site on HFE to the C terminal portion of the alpha 1 domain helix and an adjacent loop , a region distinct from the ligand binding sites on class 1 MHC and related proteins . ^^^ A biosensor derived pH dependent affinity profile for the HFE TfR interaction is discussed in terms of HFE ' s hypothesized role in intracellular trafficking . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| We recently reported that HFE , the protein defective in HH , was physically associated with the transferrin receptor ( TfR ) in duodenal crypt cells and proposed that mutations in HFE attenuate the uptake of transferrin bound iron from plasma by duodenal crypt cells , leading to up regulation of transporters for dietary iron . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| At the cell surface , HFE complexes with transferrin receptor ( TfR ) , increasing the dissociation constant of transferrin ( Tf ) for its receptor 10 fold ( Gross , C . ^^^ HFE does not remain at the cell surface , but traffics with TfR to Tf positive internal compartments ( Gross et al . , 1998 ) . ^^^ Using a HeLa cell line in which the expression of HFE is controlled by tetracycline , we show that the expression of HFE reduces 55Fe uptake from Tf by 33 % but does not affect the endocytic or exocytic rates of TfR cycling . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| A number of genes are involved in iron metabolism , including the transferrin receptor ( TFR ) and haemochromatosis ( HFE ) genes . ^^^ The HFE wild type gene product complexes with the transferrin receptor ( TF ) and two different HFE mutations ( Cys282Tyr and His63Asp ) have been found to increase the affinity of TFR for TF and increase cellular iron uptake . ^^^ In a recent study we found no associations for HFE and TFR separately , but an interaction between HFE and TFR genotypes in multiple myeloma . ^^^ Individuals carrying the HFE Tyr 282 allele ( homo and heterozygotes ) in combination with homozygosity for the TFR Ser 142 allele had an increased risk . ^^^ The risk for neoplastic disease was further increased ( OR 7 . 7 , 95 % CI = 1 . 0 59 . 9 ) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| To determine the potential role for TfR 2 in iron uptake by liver , we investigated TfR and TfR 2 expression in normal mice and murine models of dietary iron overload ( 2 % carbonyl iron ) , dietary iron deficiency ( gastric parietal cell ablation ) , and HH ( HFE / ) . ^^^ Furthermore , hepatic expression of TfR 2 was not down regulated with dietary iron loading or in the HFE / model of HH . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| One hypothesis suggests that an interaction between the transferrin receptor ( TfR ) and the haemochromatosis protein ( HFE ) regulates the level of iron loading in crypt cells . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor ( TfR ) . ^^^ These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y / H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The transferrin receptor ( TfR ) interacts with two proteins important for iron metabolism , transferrin ( Tf ) and HFE , the protein mutated in hereditary hemochromatosis . ^^^ TfR 2 has a pattern of expression and regulation that is distinct from TfR , and mutations in TfR 2 have been recognized as the cause of a non HFE linked form of hemochromatosis ( Camaschella , C . , Roetto , A . , Cali , A . , De Gobbi , M . , Garozzo , G . , Carella , M . , Majorano , N . , Totaro , A . , and Gasparini , P . ( 2000 ) Nat . ^^^ To investigate the relationship between TfR , TfR 2 , Tf , and HFE , we performed a series of binding experiments using soluble forms of these proteins . ^^^ We find no detectable binding between TfR 2 and HFE by co immunoprecipitation or using a surface plasmon resonance based assay . ^^^ These results imply that HFE regulates Tf mediated iron uptake only from the classical TfR and that TfR 2 does not compete for HFE binding in cells expressing both forms of TfR . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The wild type HFE associates and co traffics with the transferrin receptor ( TfR ) . ^^^ The mutation responsible for 83 % of HH ( C260Y ) results in the failure of HFE to form a critical disulfide bond , bind beta 2 microglobulin , bind TfR , and traffic to the cell surface . ^^^ In non polarized cells , the partnership of HFE and TfR results in decreased iron uptake into cells . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The role of HFE in iron uptake by B cells may extend beyond its known interaction with the TfR . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| For each subject we examined intragenic HFE haplotypes and transferrin receptor ( TfR ) gene polymorphisms and searched for the Y250X mutation on the TFR 2 gene . ^^^ CONCLUSION : The variable phenotypes associated with H63D homozygosity do not appear to be linked to other HFE mutations , to the TFR 2 Y250X mutation , or to HFE or TfR gene intragenic polymorphisms . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| There is evidence linking HFE with reduced iron uptake by the transferrin receptor ( TfR ) . ^^^ Using a panel of HFE and TfR monoclonal antibodies to examine human HFE ( hHFE ) expressing cell lines , we demonstrate the expression of stable and fully glycosylated TfR free and TfR associated hHFE / beta2m complexes . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Based on recent structural , biochemical , and cell biological studies , transferrin receptor ( TfR ) is a ligand for HFE . ^^^ This association directly links HFE protein to the TfR mediated regulation of iron homeostasis . ^^^ Although evidence is accumulating that binding of HFE to TfR is critical for the effects of HFE , the final pieces in the HFE puzzle have not been established . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Recently , two new types of hemochromatosis have been identified : Juvenile hemochromatosis ( JH or HFE 2 ) , which maps to chromosome 1q21 , and an adult form defined as HFE 3 , which results from mutations of the TFR 2 gene , located at 7q22 . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The wild type HH ( HFE ) protein complexes with the transferrin receptor ( TFR ) , and two HFE mutations ( Cys282Tyr and His63Asp ) have been found to increase the affinity of the TFR for transferrin resulting in an increased cellular uptake of iron . ^^^ In previous studies we found an interaction between HFE and TFR genotypes in multiple myeloma and breast and colorectal carcinomas . ^^^ In the present investigation we have studied HFE and TFR genotypes in 54 Swedish patients with HCC , using DNA from archival samples of paraffin wax blocks . ^^^ The same HFE TFR interaction as in the previously studied neoplastic disorders was found . ^^^ Individuals carrying the HFE282Tyr allele ( homo and heterozygotes ) in combination with homozygosity for the TFR Ser allele showed an increased risk for HCC ( OR = 3 . 5 ; 95 % confidence interval , CI = 1 . 3 9 . 3 ) , which was further increased in HFE Tyr homozygotes and compound ( Tyr / Asp ) heterozygotes in combination with TFR 142Ser homozygosity ( OR = 17 . 2 ; 95 % CI = 1 . 8 168 . 9 ) . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE accumulates in transferrin containing endosomes , and its overexpression in human cell lines correlates with decreased transferrin receptor ( TFR ) mediated iron uptake and decreased intracellular iron pools . ^^^ This HCMV US 2 mediated degradation of HFE leads to increased intracellular iron pools as indicated by reduced synthesis of TfR and increased ferritin synthesis . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Here we use stably transfected Chinese hamster ovary cell lines expressing both HFE and beta2M or HFE alone to study the effects of beta2M on the stability and maturation of the HFE protein and on the role of HFE in transferrin receptor 1 ( TfR 1 ) mediated iron uptake . ^^^ In agreement with prior studies on other cell lines , we found that overexpression of HFE , without overexpressing beta2M , resulted in a decrease in TfR1dependent iron uptake and in lower iron levels in the cells , as evidenced by ferritin and TfR 1 levels measured at steady state . ^^^ However , overexpression of both HFE and beta2M had the reverse effect and resulted in an increase in TfR 1 dependent iron uptake and increased iron levels in the cells . ^^^ The HFE beta2M complex did not affect the affinity of TfR 1 for transferrin or the internalization rate of transferrin bound TfR 1 . ^^^ Instead , HFE beta2M enhanced the rate of recycling of TfR 1 and resulted in an increase in the steady state level of TfR 1 at the cell surface of stably transfected cells . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| AIMS : To investigate this issue , we examined concomitant variations in duodenal cytochrome b ( Dcytb ) , divalent metal transporter 1 ( DMT 1 ) , ferroportin 1 ( FPN 1 ) , hephaestin , stimulator of Fe transport ( SFT ) , HFE , and transferrin receptor 1 ( TfR 1 ) transcripts in response to different dietary iron contents in the four mouse strains C57BL / 6 , DBA / 2 , CBA , and 129 / Sv . ^^^ Strain to strain differences were observed not only in serum transferrin saturations , with C57BL / 6 mice having the lowest values , but also in hepatic iron stores and in duodenal mRNA expression of Dcytb , DMT 1 , FPN 1 , hephaestin , HFE , and TfR 1 . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| The HFE protein binds to transferrin receptor 1 ( TfR 1 ) in competition with transferrin , and in vitro , reduces cellular iron by reducing iron uptake . ^^^ In addition , we find that the HH associated mutant H41D has lost the ability to inhibit iron release despite binding to TfR 1 as well as wild type HFE . ^^^ We conclude that HFE has two mutually exclusive functions , binding to TfR 1 in competition with Tf , or inhibition of iron release . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Iron and HFE or TfR 1 mutations as comorbid factors for development and progression of chronic hepatitis C . ^^^ Mutations or polymorphisms in the HFE gene or the TfR 1 gene may influence the accumulation of iron in the liver or other tissues or may influence chronic viral hepatitis apart from effects on iron homeostasis . ^^^ The aim of this study was to assess the role of hepatic iron , HFE and TfR 1 variations on development and progression of chronic hepatitis C infection . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE , the protein that is mutated in hereditary haemochromatosis , binds to the transferrin receptor ( TfR ) . ^^^ Here we show that wild type HFE and TfR localize in endosomes and at the basolateral membrane of a polarized duodenal epithelial cell line , whereas the primary haemochromatosis HFE mutant , and another mutant with impaired TfR binding ability accumulate in the ER / Golgi and at the basolateral membrane , respectively . ^^^ Levels of the iron storage protein ferritin are greatly reduced and those of TfR are slightly increased in cells expressing wild type HFE , but not in cells expressing either mutant . ^^^ Thus , binding to TfR is required for transport of HFE to endosomes and regulation of intracellular iron homeostasis , but not for basolateral surface expression of HFE . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Hence , the availability of plasma transferrin bound iron and the expression and function of transferrin receptors ( TfR 1 ) , HFE and DMT 1 should all contribute to the absorptive capacity of villus enterocytes . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| At variance with TFRC , interactions between TFR 2 and HFE do not occur , at least in their soluble forms . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| In iron overload , TfR 1 expression in the duodenum differed according to the presence or absence of the C282Y mutation in the HFE gene , being increased in HFE related hemochromatosis and similar to controls in non HFE related iron overload . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| METHODS : The expression and localization of HFE , TfR 1 and TfR 2 proteins in human platelets were examined using Western blotting and immunocytochemistry . ^^^ RESULTS : Human platelets expressed HFE and TfR 2 , whereas no signal for TfR 1 was found . ^^^ The presence of TfR 2 and absence of TfR 1 suggests that HFE may serve a different function in platelets compared with the other HFE positive cell types , e . g . enterocytes , macrophages and syncytiotrophoblasts . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Duodenal expression of HFE and TfR 2 ( but not TfR 1 ) in wild type mice and humans was restricted to crypt cells , in which they co localized . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Recent studies have revealed that the wild type hemochromatosis protein ( HFE ) interacts with the transferrin receptor ( TfR ) and modulates TfR mediated iron uptake by cells . ^^^ METHODS : ( 67 ) Ga and ( 59 ) Fe uptakes were measured in HeLa cells transfected with a FLAG tagged wild type HFE ( fHFE ) gene under control of a tetracycline repressible promoter . fHFE and TfR protein levels were measured by Western blotting ; cellular transferrin ( Tf ) binding sites were measured by ( 125 ) 1 Tf binding assay . ^^^ CONCLUSION : Our studies suggest that expression of wild type HFE in cells produces a decrease in ( 67 ) Ga uptake due to a reduction in available Tf binding sites for ( 67 ) Ga Tf on the TfR . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Levels of type 1 hereditary hemochromatosis gene ( HFE ) , transferrin , hepcidin , transferrin receptors 1 and 2 ( TfR 1 , TfR 2 ) , ferroportin 1 ( FPN 1 ) , divalent metal transporter 1 ( DMT 1 ) , natural resistance associated macrophage protein 1 ( Nramp 1 ) , ceruloplasmin , hephaestin , and glyceraldehyde 3 phosphate dehydrogenase ( GAPDH ) , were measured by quantitative reverse transriptase polyerase chain reaction ( qRT PCR ) . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Furthermore , duodenal hephaestin and TfR 1 mRNA expression and hepatic hepcidin mRNA expression remained unaltered , while the duodenal mRNA expression of the brush border ferric reductase Dcytb was significantly increased in Hfe ( / ) mice . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Fe Tf competes for binding to TfR with HFE , the protein mutated in the iron overload disease hereditary hemochromatosis . ^^^ We used a quantitative surface plasmon resonance assay to determine the binding affinities of an extensive set of site directed TfR mutants to HFE and Fe Tf at pH 7 . 4 and to apo Tf at pH 6 . 3 . ^^^ These results confirm the previous finding that Fe Tf and HFE compete for the receptor by binding to an overlapping site on the TfR helical domain . ^^^ Spatially distant mutations in the TfR protease like domain affect binding of Fe Tf , but not iron loaded Tf C lobe , apo Tf , or HFE , and mutations at the edge of the TfR helical domain affect binding of apo Tf , but not Fe Tf or HFE . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| In this study we evaluated whether polymorphisms in the hemochromatosis gene HFE and the transferrin receptor gene TFR 1 are associated with these typical findings . ^^^ The study considered 246 HCV infected patients and 200 blood donors as controls , in which C282Y , H63D , and S65C mutations ( HFE ) and the S142G polymorphism ( TFR 1 ) were detected . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Four genes involved in iron homeostasis were included in the 50 differentially expressed genes [ hemochromatosis ( Hfe ) , diaphorase 1 , transferrin receptor ( Trfr ) 2 , and protoporphyrinogen oxidase ] and two additional iron related genes did not quite meet the stringent criteria for differential expression ( Trfr and lactotransferrin ) . ^^^ Hfe and Trfr mRNA levels and liver iron were negatively correlated with fat mass . ^^^ Variation in obesity phenotypes explained 49 % , 40 % , and 37 % , respectively , of the variance in Hfe , Lep , and Trfr mRNA levels . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| A non classical class 1 MHC molecule , the hemochromatosis factor HFE , has been shown to regulate iron metabolism , potentially via its direct interaction with the transferrin receptor ( TfR ) . ^^^ In this study , we demonstrate that a soluble beta2microglobulin HFE monochain ( sHFE ) folds with beta2microglobulin ( beta2m ) and associates with the TfR , indicating that the transmembrane and cytoplasmic domains are not necessary for assembly and trafficking through the ER Golgi network . ^^^ The sHFE monochain was effective in reducing Tf uptake into cells , however this did not correlate to any changes in TfR or ferritin synthesis , in contrast to the HFE induced increase and decrease of TfR and ferritin , respectively . ^^^ These findings of incongruent sHFE activity suggest that either variation in affinity binding of sHFE to TfR prevents efficient modulation of iron regulated proteins or that HFE has multiple functions some of which may be independent of TfR but dependent on interactions within the endosomal compartment for effective modulation of iron metabolism . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE affects the interaction of transferrin bound iron with transferrin receptors ( TfR ) thereby modulating iron uptake . ^^^ Mice with high duodenal HFE mRNA expression presented with significantly higher levels of TfR and DMT 1 mRNAs and an increased IRP 1 binding affinity as compared to mice with low HFE levels . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| This mechanism is different from that observed with the ferric holotransferrin and implies that the interaction between TFR and bismuth loaded transferrin probably takes place on the helical domain of the receptor which is specific for the C site of transferrin and HFE . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| In the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial , 679 persons with advanced distal adenoma and 697 control persons were genotyped for the two major HFE mutations ( C282Y and H63D ) , one HFE polymorphism ( IVS2+4 ) , and one polymorphism ( G142S ) in the transferrin receptor gene ( TFRC ) . ^^^ Stratification of HFE genotype by TFRC genotype did not change the results . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND AND OBJECTIVES : The HFE protein interacts with the transferrin receptor ( TfR ) to regulate cellular iron uptake . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| In HFE / mice hepcidin formation was diminished upon iron challenge which was associated with decreased hepatic transferrin receptor ( TfR ) 2 levels . ^^^ Accordingly , HFE / mice presented with high duodenal Dcytb and DMT 1 levels , and increased IRP and TfR expression , suggesting iron deficiency in the enterocyte and increased iron absorption . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Case control studies have reported associations between HFE mutations C282Y / H63D and several cancers , some of which in interaction with the transferrin receptor gene TFRC or dietary iron intake . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Several iron transporters and regulators were recently characterized , including DMT 1 and ferroportin / Ireg1 that transport iron through membranes , and HFE that regulates TfR mediated iron uptake . ^^^ In this study we demonstrate that in a differentiated choriocarcinoma cell line BeWo , HFE , and TfR are localized mainly in recycling endosomes and a small percentage of these complexes is observed in late endosomes with DMT 1 while in trophoblast cells , the level of TfR is significantly lower and it is detected with HFE and DMT 1 mainly in late endosomes . ^^^ Most interestingly , TfR and HFE , as well as TfR and DMT 1 interact in placental trophoblast cells . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| To understand the role of hemochromatosis and transferrin receptor system mutations in breast cancer , we analyzed 19 sequence variations at HFE , TFR 1 , TFR 2 , and FPN 1 and compared genotype frequencies between cases and controls in a German population . ^^^ The frequencies of HFE at His63Asp , Ser65Cys , and Cys282Tyr , and of TFR 1 at Ser142Gly minor alleles in this German population were 15 . 9 % , 1 . 8 % , 5 . 6 % , and 46 . 0 % , respectively . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Whereas a recent study reported an increased risk of colorectal cancer associated with any HFE germ line mutation ( C282Y or H63D ) , other investigators have concluded there is no increased risk , or that any increase is dependent on polymorphisms in HFE interacting genes such as the transferrin receptor ( TFR ) . ^^^ TFR gene polymorphism was not an independent risk factor and did not modify the disease risk associated with HFE mutation . . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Experiments using cells over expressing wild type HFE confirm the existence of beta2microglobulin ( beta2m ) / HFE and HFE / transferrin receptor 1 ( TfR 1 ) interactions , as well as the capacity of HFE to reduce transferrin mediated iron uptake . ^^^ |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| We also demonstrated that MMTV entry is independent of transferrin , iron , and the TfR 1 cofactor hereditary hematochromatosis HFE protein . ^^^ Using chimeric mouse / human hybrid TfR 1 constructs , we determined the site of interaction with MMTV and found that it maps to two segments physically disparate from the TfR and HFE binding sites . ^^^ |
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| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE was on some parts of the basal STB and , where present , HFE clearly colocalised with FPN but not TfR 1 . ^^^ |
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| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| HFE is the principal regulator of iron homeostasis , and the process involves interaction with transferrin receptor ( TfR ) 1 , transferrin receptor ( TfR ) 2 , and beta 2 microglobulin ( beta2M ) . ^^^ In the present study , the expression of HFE and the HFE interacting proteins TfR 1 , TfR 2 , and beta2M were analyzed in mouse retina . ^^^ Expression of the HFE interacting proteins TfR 1 , TfR 2 , and beta2M was also evident in the retina . ^^^ The specific localization of HFE and its interacting proteins , TfR 1 and TfR 2 , at the basolateral membrane of RPE is relevant to the regulation of iron homeostasis in this cell . ^^^ |
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| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| This is accomplished by comparing the differences between delta G degrees B , w and delta G degrees B , hh ( or delta G degrees B , dh ) with the water to hexane solvent transfer free energies of the quinones ( delta G degrees tr , Q ) . ^^^ Values of delta G degrees B , hh delta G degrees B , w are linearly correlated with delta G degrees tr , Q ( slope , 0 . 78 + / 0 . 04 ; ordinate intercept , 0 . 13 + / 0 . 12 kcal / mol ) . ^^^ |
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| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| Transient recovery ( TR ) of evoked synaptic potential during the late stage of hypoxic hypoglycemia ( HH ) insult was investigated in rat hippocampal slices using extracellular recording methods . ^^^ TR was observed in association with a rapid deterioration of antidromic population spikes ( aPSs ) following HH insult . ^^^ The evidence thus suggests that the underlying mechanisms of TR appearance during HH insult are highly correlated with rapid energy depletion . . ^^^ |
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| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q30201 and P02786 |
Pubmed |
SVM Score :0.0 |
| NA |
|