Recombinant Human Proton-coupled folate transporter (SLC46A1), partial

1. Low PCFT expression is associated with treatment response in mesothelioma. PMID: 28945836
2. our results demonstrate the substantial therapeutic potential of novel 6-substituted pyrrolo[2,3-d]pyrimidine antifolates with dual targeting of PCFT and FRalpha toward Epithelial ovarian cancer that express a range of FRalpha, along with PCFT, as well as cisplatin resistance PMID: 28138029
3. We found that purified detergent solubilized PCFT was able to bind folic acid, thus indicating a functionally active protein. To assess the oligomeric state negative stain electron microscopy was performed which showed a particle with the size of a PCFT dimer. PMID: 29208467
4. The 8th transmembrane helix of PCFT plays an important role in defining the aqueous channel and the folate binding pocket. PMID: 28802835
5. The hydrophobicity of the PCFT W299 residue is important for function suggesting that during the transport cycle this residue interacts with the lipid membrane thereby impacting on the oscillation of the carrier and, indirectly, on the folate binding pocket. PMID: 27251438
6. we observed nominally significant (but not definitive) associations between SLC46A1 SNPs and NTDs and oral clefts, and this finding warrants follow-up in other populations. PMID: 26789141
7. 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. PMID: 26884338
8. 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. PMID: 26193446
9. Report sustained inhibition of PCFT by myricetin. PMID: 25801697
10. 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. PMID: 25697897
11. 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. PMID: 25877470
12. the RFC1 G80A polymorphism does not seem to be a good marker of MTX-related toxicity in pediatric ALL. PMID: 24597986
13. 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. PMID: 25608532
14. SLC46A1 genotype may help to identify patients with increased risk of methotrexate-related toxicity. PMID: 25124723
15. Data indicate that 28/33 cysteine-less proton-coupled folate transporter (PCFT) mutant HeLa cells were active for [(3)H]methotrexate uptake. PMID: 25053408
16. The molecular bases for methotrexate resistance associated with loss of SLC19A1 transport and for hereditary folate malabsorption, attributable to mutant SLC46A1, were determned (review). PMID: 24396145
17. SLC46A1 SNP had a statistically significant association with HDL plasma levels. PMID: 23656756
18. At weakly acidic pH (6.5), bisulfite and nitrite exhibited much stronger inhibition of PCFT-mediated transport. PMID: 23609145
19. 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. PMID: 23552283
20. 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. PMID: 23313509
21. The monomeric state of proton-coupled folate transporter is the functional state, substrate translocation does not depend on homo-oligomerization. PMID: 23601781
22. PCFT is abundantly expressed in human tumors and is active at pHs characterizing the tumor microenvironment PMID: 22954694
23. Loss of intrinsic Gly338Cys-PCFT function is due solely to impaired oscillation of the carrier between its conformational states. PMID: 22843796
24. 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. PMID: 22785121
25. HCP1 is involved in low-affinity heme-Fe uptake by Caco-2 cells. PMID: 22496243
26. 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. PMID: 22345511
27. Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter. PMID: 22179615
28. PCFT 928GG genotype had significantly higher plasma Hcy concentrations compared with carriers of the A allele. PMID: 21338559
29. 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 PMID: 21489556
30. 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). PMID: 21333572
31. Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function. PMID: 21602279
32. Data show that the loss of activity of mutant PCFTs was shown to be due to impaired protein stability and expression. PMID: 21256110
33. 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. PMID: 20795774
34. 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. PMID: 20805364
35. the obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1 PMID: 20724482
36. 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. PMID: 20686069
37. analyses establish a PCFT secondary structure of 12 transmembrane domains with the N- and C- termini directed to the cytoplasm PMID: 20225891
38. 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 PMID: 20005757
39. Using immunohistochemistry, PCFT was localized to microvillous plasma membrane of syncytiotrophoblasts during first trimester and at term. PMID: 20036773
40. 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) PMID: 19762432
41. A loss-of-function mutation in PCFT/HCP1 is the molecular basis for hereditary folate malabsorption in a family with this disease. PMID: 17129779
42. HCP1 expression in different cells implies a functional role in tissues other than the duodenum PMID: 17156779
43. 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. PMID: 17335806
44. Mutations in the PCFT gene is associated with malabsorption syndromes PMID: 17446347
45. Data suggest that hPCFT/HCP1 is responsible for the intestinal absorption of folate and also methotrexate. PMID: 17475902
46. 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. PMID: 17947394
47. 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. PMID: 18003745
48. 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. PMID: 18650265
49. 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. PMID: 18718264
50. These findings constitute the first demonstration of the dominant epigenetic silencing of the PCFT gene in leukemia cells. PMID: 18817749

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HGNC: 30521

OMIM: 229050

KEGG: hsa:113235

STRING: 9606.ENSP00000395653

UniGene: Hs.446689