Property Summary

NCBI Gene PubMed Count 62
PubMed Score 163.07
PubTator Score 144.72

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma 1.316 1.3e-04
adrenocortical carcinoma -1.029 2.1e-03
group 4 medulloblastoma 1.300 5.3e-05

Gene RIF (54)

PMID Text
26884338 A homology model of PCFT, based upon the Escherichia coliglycerol 3-phosphate transporter structure, predicted that PCFT transmembrane domains (TMDs) 1, 2, 7, and 11 form an extracellular gate in the inward-open conformation.
26193446 We conclude that SLC46A1/PCFT and SLC19A1/RFC-1 are associated with DFS of patients with colorectal cancer and hypothesize that poor response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of these genes.
25877470 results imply that TMDs 3 and 6 provide critical interfaces for formation of hPCFT oligomers, which might be facilitated by the GXXXG motifs in TMD2 and TMD4.
25801697 Report sustained inhibition of PCFT by myricetin.
25697897 this is the first study to simultaneously evaluate both DNA methylation and protein expression of all three folate transporter genes, FOLR1, PCFT, and RFC1, in colorectal cancer.
25608532 The current study addresses the role of Tyr residues in SLC46A1 function; and identifies four residues that enhance the affinity of the carrier for its substrates and decrease the rate at which the carrier oscillates between its conformational states.
25124723 SLC46A1 genotype may help to identify patients with increased risk of methotrexate-related toxicity.
25053408 Data indicate that 28/33 cysteine-less proton-coupled folate transporter (PCFT) mutant HeLa cells were active for [(3)H]methotrexate uptake.
24597986 the RFC1 G80A polymorphism does not seem to be a good marker of MTX-related toxicity in pediatric ALL.
24396145 The molecular bases for methotrexate resistance associated with loss of SLC19A1 transport and for hereditary folate malabsorption, attributable to mutant SLC46A1, were determned (review).
23656756 SLC46A1 SNP had a statistically significant association with HDL plasma levels.
23609145 At weakly acidic pH (6.5), bisulfite and nitrite exhibited much stronger inhibition of PCFT-mediated transport.
23601781 The monomeric state of proton-coupled folate transporter is the functional state, substrate translocation does not depend on homo-oligomerization.
23552283 Two loss-of-function mutations in the fourth transmembrane domain of proton-coupled folate transporter (PCFT) play a role in hereditary folate malabsorption in subjects with this disorder.
23313509 These results suggest that the activity of PCFT promoter is basically induced by KLF4 and the gradiented expression profile of PCFT may be at least in part accounted for by those of HNF4alpha, CDX2 and C/EBPalpha.
22954694 PCFT is abundantly expressed in human tumors and is active at pHs characterizing the tumor microenvironment
22843796 Loss of intrinsic Gly338Cys-PCFT function is due solely to impaired oscillation of the carrier between its conformational states.
22785121 The role of GXXG motif is consistent with a molecular structural model in which this motif and Ile188 are accessible to the PCFT aqueous translocation pathway.
22496243 HCP1 is involved in low-affinity heme-Fe uptake by Caco-2 cells.
22345511 the P425R-PCFT mutation produces a conformational change that fully preserves pemetrexed binding but markedly impairs binding of methotrexate and other folates to the carrier.
22179615 Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter.
21602279 Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function.
21489556 These findings are consistent with a common mutation in the PCFT gene causing hereditary folate malabsorption that has disseminated to Puerto Ricans who have migrated to mainland United States
21338559 PCFT 928GG genotype had significantly higher plasma Hcy concentrations compared with carriers of the A allele.
21333572 novel mutations are described in three subjects with folate malabsorption: A335D/N68Kfs (c.1004C>A/c.204-205delCC), compound heterozygous mutations, and two homozygous PCFT mutations, G338R (c.1012G>C) and E9Gfs (c.17-18insC).
21256110 Data show that the loss of activity of mutant PCFTs was shown to be due to impaired protein stability and expression.
20805364 D156 plays a critical role in PCFT protein stability, and D109, located in the first intracellular loop between the second and third transmembrane domains, is absolutely required for PCFT function.
20795774 The report on a Turkish family with 2 children with HFM who have a novel homozygous frameshift mutation (c.204 205delCC) in the PCFT gene.
20724482 the obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1
20686069 Data suggest that mutation of the R376 residue of SLC46A1 to Gln impairs proton binding which modulates the folate-binding pocket and depresses the rate of conformational alteration of the carrier.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20225891 analyses establish a PCFT secondary structure of 12 transmembrane domains with the N- and C- termini directed to the cytoplasm
20036773 Using immunohistochemistry, PCFT was localized to microvillous plasma membrane of syncytiotrophoblasts during first trimester and at term.
20005757 Direct sequencing of PCFT revealed a novel homozygous frameshift mutation (c.194dupG) at a mononucleotide repeat in exon 1 predicted to result in a truncated protein (p.Cys66LeufsX99) causing hereditary folate malabsorptionl
19913121 Observational study of gene-disease association. (HuGE Navigator)
19762432 hPCFT transporter activity can be modulated by many drugs in clinical use, and expression of this transporter in the gastrointestinal tract is higher in the duodenum than more distal sites (duodenum > ileum > colon)
19643086 This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.
19508863 These findings constitute the first demonstration that a basic amino acid at position 113 is required for folate substrate binding by SLC46A1.
19403800 Observations suggest that the E185 residue plays an important role in the coupled flows of protons and folate mediated by SLC46A1.
19176287 The entire HCP1 coding region was examined in 788 participants from the HEIRS study. 8 different heterozygous variants were found; 5 non-synonymous coding-region variants displayed high transferrin saturations.
19176287 Observational study of gene-disease association. (HuGE Navigator)
19074442 that PCFT plays a role in FRalpha-mediated endocytosis by serving as a route of export of folates from acidified endosomes
18842806 Observational study of gene-disease association. (HuGE Navigator)
18817749 These findings constitute the first demonstration of the dominant epigenetic silencing of the PCFT gene in leukemia cells.
18718264 HFM was shown to be due to loss-of-function mutations in a proton-coupled folate transporter (PCFT),[3] and [4] allowing the possibility of rapid diagnosis and correlations among specific mutations, clinical manifestations, and outcome.
18650265 Intestinal folate uptake process undergoes differentiation-dependent regulation and that this regulation is mediated via changes in the level of expression of both the RFC and PCFT.
18187620 Knockdown of solute carrier family 46 (folate transporter), member 1 (SLC46A1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells
18003745 Present information regarding structure-function and membrane targeting of the hPCFT polypeptide, as well as the mechanisms that control its steady-state expression in polarized cells.
17947394 HCP-1 expression in human macrophages is downregulated by TLR agonists & IFN-gamma, upregulated by dexamethasone. In early endosomes, it colocalizes with endocytosed Hb-haptoglobin (Hp) complexes, taken up by the CD163 scavenger receptor pathway.
17475902 Data suggest that hPCFT/HCP1 is responsible for the intestinal absorption of folate and also methotrexate.
17446347 Mutations in the PCFT gene is associated with malabsorption syndromes
17335806 Our data revealed low-level wider expression of human HCP1 transcript in multiple tissues suggesting that it is responsible for heme transport in the body, not the intestine alone.
17156779 HCP1 expression in different cells implies a functional role in tissues other than the duodenum
17129779 A loss-of-function mutation in PCFT/HCP1 is the molecular basis for hereditary folate malabsorption in a family with this disease.

AA Sequence

MEGSASPPEKPRARPAAAVLCRGPVEPLVFLANFALVLQGPLTTQYLWHRFSADLGYNGTRQRGGCSNRS      1 - 70
ADPTMQEVETLTSHWTLYMNVGGFLVGLFSSTLLGAWSDSVGRRPLLVLASLGLLLQALVSVFVVQLQLH     71 - 140
VGYFVLGRILCALLGDFGGLLAASFASVADVSSSRSRTFRMALLEASIGVAGMLASLLGGHWLRAQGYAN    141 - 210
PFWLALALLIAMTLYAAFCFGETLKEPKSTRLFTFRHHRSIVQLYVAPAPEKSRKHLALYSLAIFVVITV    211 - 280
HFGAQDILTLYELSTPLCWDSKLIGYGSAAQHLPYLTSLLALKLLQYCLADAWVAEIGLAFNILGMVVFA    281 - 350
FATITPLMFTGYGLLFLSLVITPVIRAKLSKLVRETEQGALFSAVACVNSLAMLTASGIFNSLYPATLNF    351 - 420
MKGFPFLLGAGLLLIPAVLIGMLEKADPHLEFQQFPQSP                                   421 - 459
//

Text Mined References (69)

PMID Year Title
26884338 2016 Identification of an Extracellular Gate for the Proton-coupled Folate Transporter (PCFT-SLC46A1) by Cysteine Cross-linking.
26193446 2015 Expression of Folate Pathway Genes in Stage III Colorectal Cancer Correlates with Recurrence Status Following Adjuvant Bolus 5-FU-Based Chemotherapy.
25877470 2015 Structural determinants of human proton-coupled folate transporter oligomerization: role of GXXXG motifs and identification of oligomeric interfaces at transmembrane domains 3 and 6.
25801697 2015 Sustained inhibition of proton-coupled folate transporter by myricetin.
25697897 2015 DNA methylation and expression of the folate transporter genes in colorectal cancer.
25608532 2015 Identification of Tyr residues that enhance folate substrate binding and constrain oscillation of the proton-coupled folate transporter (PCFT-SLC46A1).
25124723 2014 SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients.
25080503 2014 Meta-analysis of genome-wide association studies identifies two loci associated with circulating osteoprotegerin levels.
25053408 2014 Substituted cysteine accessibility reveals a novel transmembrane 2-3 reentrant loop and functional role for transmembrane domain 2 in the human proton-coupled folate transporter.
24597986 2014 Association between reduced folate carrier G80A polymorphism and methotrexate toxicity in childhood acute lymphoblastic leukemia: a meta-analysis.
24396145 2014 The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.
23656756 2013 Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults.
23609145 2013 Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions.
23601781 2013 The monomeric state of the proton-coupled folate transporter represents the functional unit in the plasma membrane.
23552283 2013 Role of the fourth transmembrane domain in proton-coupled folate transporter function as assessed by the substituted cysteine accessibility method.
23313509 2013 Transcriptional regulation of PCFT by KLF4, HNF4?, CDX2 and C/EBP?: implication in its site-specific expression in the small intestine.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22954694 2012 The human proton-coupled folate transporter: Biology and therapeutic applications to cancer.
22843796 2012 Functional roles of the A335 and G338 residues of the proton-coupled folate transporter (PCFT-SLC46A1) mutated in hereditary folate malabsorption.
22814378 2012 N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.
22785121 2012 Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1).
22496243 2012 Heme carrier protein 1 transports heme and is involved in heme-Fe metabolism.
22345511 2012 A P425R mutation of the proton-coupled folate transporter causing hereditary folate malabsorption produces a highly selective alteration in folate binding.
22179615 2012 Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter.
21602279 2011 Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function.
21489556 2011 Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico.
21338559 2011 Interactions between genetic variants of folate metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican population.
21333572 2011 Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption.
21256110 2011 Vulnerability of the cysteine-less proton-coupled folate transporter (PCFT-SLC46A1) to mutational stress associated with the substituted cysteine accessibility method.
20805364 2010 Functional roles of aspartate residues of the proton-coupled folate transporter (PCFT-SLC46A1); a D156Y mutation causing hereditary folate malabsorption.
20795774 2010 Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish siblings with hereditary folate malabsorption.
20724482 2010 The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1.
20686069 2010 Properties of the Arg376 residue of the proton-coupled folate transporter (PCFT-SLC46A1) and a glutamine mutant causing hereditary folate malabsorption.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20225891 2010 Membrane topological analysis of the proton-coupled folate transporter (PCFT-SLC46A1) by the substituted cysteine accessibility method.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20036773 2010 Expression of folate transporters in human placenta and implications for homocysteine metabolism.
20005757 2010 A novel PCFT gene mutation (p.Cys66LeufsX99) causing hereditary folate malabsorption.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19762432 2010 The human proton-coupled folate transporter (hPCFT): modulation of intestinal expression and function by drugs.
19643086 2009 Functional elements in the minimal promoter of the human proton-coupled folate transporter.
19581412 2009 Quantitative proteomics identifies a Dab2/integrin module regulating cell migration.
19508863 2009 Hereditary folate malabsorption: a positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding.
19403800 2009 Role of the glutamate 185 residue in proton translocation mediated by the proton-coupled folate transporter SLC46A1.
19389703 2009 The functional roles of the His247 and His281 residues in folate and proton translocation mediated by the human proton-coupled folate transporter SLC46A1.
19371039 2009 Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transporter for cellular entry.
19176287 Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19074442 2009 A role for the proton-coupled folate transporter (PCFT-SLC46A1) in folate receptor-mediated endocytosis.
18842806 2008 Associations between single nucleotide polymorphisms in folate uptake and metabolizing genes with blood folate, homocysteine, and DNA uracil concentrations.
18817749 2008 PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells.
18718264 2008 The clinical course and genetic defect in the PCFT gene in a 27-year-old woman with hereditary folate malabsorption.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18650265 2008 Differentiation-dependent regulation of the intestinal folate uptake process: studies with Caco-2 cells and native mouse intestine.
18559978 2008 A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function.
18003745 2008 Apical membrane targeting and trafficking of the human proton-coupled transporter in polarized epithelia.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17947394 2008 Heme carrier protein (HCP-1) spatially interacts with the CD163 hemoglobin uptake pathway and is a target of inflammatory macrophage activation.
17475902 2007 Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter.
17446347 2007 The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption.
17335806 2007 Heme carrier protein 1 (HCP1) expression and functional analysis in the retina and retinal pigment epithelium.
17156779 2006 Haem carrier protein 1 (HCP1): Expression and functional studies in cultured cells.
17129779 2006 Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16143108 2005 Identification of an intestinal heme transporter.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.