Affinage

Showing SLC19A1 — RFC is a alias.

SLC19A1

Reduced folate transporter · UniProt P41440

Length
591 aa
Mass
64.9 kDa
Annotated
2026-06-10
100 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC19A1 (reduced folate carrier, RFC1) is a plasma-membrane anion exchanger that serves as the major cellular importer of reduced folates and antifolate drugs, coupling substrate import to anion export with intracellular thiamine pyrophosphate as the preferred counter-transport substrate (PMID:36071163, PMID:36575193). Cryo-EM structures of the apo, folate-bound, antifolate-bound, and cyclic-dinucleotide-bound states show that folates and antifolates bind as monomers in one pocket while CDNs bind as a compact dual-molecule unit in a distinct cavity, explaining the divergent recognition of these substrate classes (PMID:36071163, PMID:36265513, PMID:36575193); selectivity is set by specific residues, including a single position between transmembrane helices 7 and 8 that tunes the affinity for methotrexate influx (PMID:9446553). Beyond its folate role, SLC19A1 is the principal importer of cyclic dinucleotides such as 2'3'-cGAMP, and its activity governs STING-pathway responses to extracellular CDNs, with uptake competitively blocked by folates and antifolates (PMID:31511694, PMID:31126740). The transporter is bidirectional: under severe folate deprivation it paradoxically exports intracellular folate monoglutamates, becoming cytotoxic, and its expression is down-regulated as an adaptive response (PMID:18499665). Surface abundance and function are controlled post-translationally by mTORC1/mTORC2 (PMID:27562465) and transcriptionally by the vitamin D receptor (PMID:28885847) and NRF-1/PGC-1α (PMID:32543769), with additional post-transcriptional repression by miR-595 (PMID:29345051). Through control of one-carbon metabolism, SLC19A1 also influences DNA methylation and proinflammatory gene expression in adipocytes (PMID:29121255), and is required for germline proliferation and viability in the C. elegans ortholog folt-1 (PMID:20441590).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Established the first structure-function determinant of antifolate handling by pinpointing a single residue that governs substrate binding on the extracellular face of the carrier.

    Evidence Site-specific transfection of murine RFC-1 variant constructs (Ser297 vs Asn297) into transport-deficient cells with influx Km measurements

    PMID:9446553

    Open questions at the time
    • Did not provide an atomic structure of the binding pocket
    • Limited to methotrexate among diverse antifolates
  2. 1998 Medium

    Defined the transcriptional architecture of the gene, showing multiple promoters drive alternatively spliced transcripts with differing basal activity.

    Evidence Genomic sequencing, primer extension, and luciferase reporter deletion analysis in transient transfections

    PMID:9602167

    Open questions at the time
    • Did not identify the trans-acting factors binding each promoter
    • Tissue-specific promoter usage not resolved
  3. 2001 Medium

    Showed RFC-mediated transport adopts distinct pH-dependent activities, indicating tissue-specific modulation of the carrier.

    Evidence Stable RFC1 transfection into IEC-6 and L1210 cells with radiolabeled influx assays at varying pH

    PMID:11600421

    Open questions at the time
    • Molecular basis of the low-pH activity unresolved
    • Whether a distinct transporter contributes was not excluded
  4. 2003 Medium

    Mapped the developmental expression of RFC, linking the carrier to folate supply during embryogenesis and to a restricted retinal pigment epithelium localization.

    Evidence In situ hybridization and immunolocalization across mouse embryonic stages E9.0–E12.5

    PMID:12887734

    Open questions at the time
    • Expression pattern alone does not establish functional requirement in each tissue
    • No loss-of-function phenotype in this study
  5. 2008 Medium

    Revealed RFC as a bidirectional transporter that can export folates and become cytotoxic under deprivation, redefining it beyond a unidirectional importer.

    Evidence Ectopic RFC vs FR-alpha overexpression in folate-free medium with viability assays, RT-PCR, MTX influx, and biomodeling

    PMID:18499665

    Open questions at the time
    • Physiological contexts where export dominates not defined
    • Counter-anion driving export not identified here
  6. 2010 Medium

    Demonstrated an in vivo organismal requirement for the carrier in germline proliferation and viability using a genetic ortholog knockout.

    Evidence folt-1(ok1460) knockout in C. elegans with germline microscopy, lifespan, mating, and apoptosis assays

    PMID:20441590

    Open questions at the time
    • Ortholog phenotype may not fully map to mammalian SLC19A1
    • Mechanism linking folate transport to proliferation defect not dissected
  7. 2011 Medium

    Connected RFC function to membrane microdomain localization, showing lipid-raft residence and its disruption by chronic ethanol.

    Evidence Colonic apical membrane vesicle transport assays, lipid-raft floatation, and immunoblotting in a rat ethanol-feeding model

    PMID:21069807

    Open questions at the time
    • Direct requirement of raft localization for transport not tested
    • Mechanism of ethanol-induced raft depletion unknown
  8. 2016 Medium

    Identified mTORC1/mTORC2 as upstream regulators that control RFC surface abundance and thus folate uptake.

    Evidence siRNA silencing of raptor/rictor in primary human trophoblasts with folate uptake assays and plasma-membrane fractionation

    PMID:27562465

    Open questions at the time
    • Direct molecular link between mTOR and trafficking not defined
    • Generality beyond trophoblasts untested
  9. 2017 Medium

    Established VDR as a direct transcriptional activator of SLC19A1 at the blood-brain barrier.

    Evidence Calcitriol treatment and VDR siRNA in hCMEC/D3 cells and mouse brain capillaries with MTX uptake, RT-PCR, and Western blot

    PMID:28885847

    Open questions at the time
    • VDR response element not mapped on the promoter
    • Single laboratory
  10. 2018 Medium

    Linked SLC19A1 to epigenetic and inflammatory control by showing its loss perturbs one-carbon metabolism, drives DNA hypermethylation, and induces proinflammatory genes.

    Evidence siRNA knockdown in human adipocytes with metabolomics, DNA methylation pyrosequencing, microarray, reporter assays, and cytokine ELISA

    PMID:29121255

    Open questions at the time
    • Causal chain from methylation to inflammation in vivo not established
    • Generality beyond adipocytes untested
  11. 2018 Medium

    Identified miR-595 as a post-transcriptional repressor of SLC19A1 that modulates methotrexate accumulation and sensitivity.

    Evidence Luciferase 3'-UTR reporter, miR-595 mimic/inhibitor, MTX quantification, and viability assays in CEM/C1 leukemia cells

    PMID:29345051

    Open questions at the time
    • Clinical relevance to MTX resistance not validated
    • Single cell-line context
  12. 2019 High

    Discovered an entirely new transport function: SLC19A1 is the major importer of cyclic dinucleotides, coupling the carrier to STING-dependent innate immune signaling.

    Evidence Two concurrent genome-wide CRISPR screens with CDN uptake assays, STING functional readouts, and competition by folates/antifolates in human cells

    PMID:31126740 PMID:31511694

    Open questions at the time
    • Whether additional transporters contribute to CDN uptake not fully resolved
    • In vivo immune consequences not addressed in these studies
  13. 2022 High

    Provided the structural basis for substrate recognition and the anion-exchange mechanism, defining distinct binding modes for folates/antifolates (monomeric) versus CDNs (dual-molecule unit) and the coupled counter-substrate.

    Evidence Cryo-EM of apo, methotrexate, 5-methyltetrahydrofolate, antifolate, and CDN complexes with MD simulations, mutagenesis, and transport-coupling assays

    PMID:36071163 PMID:36265513 PMID:36575193

    Open questions at the time
    • Dynamics of the full alternating-access cycle not captured
    • Structural basis of bidirectional export not separately resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse upstream regulatory inputs (mTOR, VDR, NRF-1/PGC-1α, miR-595, lipid rafts) are integrated to set SLC19A1 surface activity in specific tissues, and how its CDN-import and folate-transport roles are physiologically balanced, remains unresolved.
  • No unified model coupling transcriptional and trafficking control
  • In vivo significance of CDN import for innate immunity not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 8 GO:0008289 lipid binding 3
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-382551 Transport of small molecules 3 R-HSA-168256 Immune System 2 R-HSA-1430728 Metabolism 1

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 SLC19A1 (reduced folate carrier) is the major transporter of cyclic dinucleotides (CDNs), including 2'3'-cGAMP, into cells. Identified by genome-wide CRISPR-interference screen; depletion inhibits CDN uptake and STING-pathway functional responses, while overexpression increases both uptake and responses. CDN uptake is inhibited by folates, sulfasalazine, and methotrexate, consistent with competition at the same transporter. Genome-wide CRISPR-interference screen, CDN uptake assays, STING-pathway functional readouts, overexpression and depletion experiments in human cell lines and primary cells Nature High 31511694
2019 SLC19A1 is the first known importer of cGAMP and other CDNs (including the investigational drug 2'3'-CDAS), confirmed by genome-wide CRISPR screen in a second independent study. Genome-wide CRISPR screen, CDN import assays Molecular cell High 31126740
2022 Cryo-EM structures of human SLC19A1 in apo state and in complex with methotrexate reveal the molecular basis of substrate recognition: RFC functions as an anion exchanger coupling folate/antifolate import to anion export; key residues determining transport selectivity among folates and antifolates were identified. Combined with molecular dynamics simulations and functional experiments. Cryo-electron microscopy structure determination, molecular dynamics simulations, functional transport assays Nature High 36071163
2022 Cryo-EM structures of human SLC19A1 in substrate-free state and complexed with multiple CDNs, a natural folate (5-methyltetrahydrofolate), and a new-generation antifolate reveal that two CDN molecules bind as a compact dual-molecule unit within the transporter cavity, whereas folate and antifolate bind as monomers in a distinct pocket. Mutagenesis studies confirmed divergent recognition mechanisms for CDN-type versus folate-type substrates. Cryo-electron microscopy, mutagenesis, binding/functional assays Nature High 36265513
2022 Cryo-EM structure of SLC19A1 with 5-methyltetrahydrofolate identifies critical residues for folate substrate recognition; two variant residues among SLC19 subfamily members designate specificity for folate. Intracellular thiamine pyrophosphate was identified as the preferred coupled (counter-transport) substrate for folate import by SLC19A1. Cryo-EM structure determination, mutagenesis, transport coupling assays Cell discovery High 36575193
1998 A single amino acid difference (Ser297 vs. Asn297, between the 7th and 8th membrane-spanning helices) in the murine RFC-1 (SLC19A1) protein selectively alters the apparent Km for methotrexate influx without affecting Vmax or efflux, establishing this residue as a determinant of antifolate binding on the extracellular face of the transporter. cDNA sequencing, site-specific transfection of RFC-1 constructs into transport-deficient cells, influx Km measurements with radiolabeled substrates, Western blotting The Journal of biological chemistry High 9446553
2001 Expression of the reduced folate carrier SLC19A1 (RFC1) in intestinal IEC-6 cells produces two distinct transport activities: one at low pH (pH 5.5) inhibited by folic acid, and one at neutral pH (pH 7.4), demonstrating that tissue-specific modulators determine the pH profile of RFC1-mediated transport. Stable transfection of RFC1 construct into IEC-6 and L1210 cells, radiolabeled substrate influx assays at varying pH, inhibition studies with folic acid and metabolic inhibitors American journal of physiology. Cell physiology Medium 11600421
2008 RFC (SLC19A1) acts as a bidirectional anion transporter that becomes cytotoxic under severe folate deprivation by efficiently exporting intracellular folate monoglutamates out of cells. Ectopic overexpression of RFC (but not unidirectional folate receptor alpha) caused ~15-fold decline in cell viability in folate-free medium. Down-regulation of RFC mRNA and transport activity occurs as an adaptive response to folate deprivation. Ectopic overexpression of RFC vs. folate receptor alpha in folate-free vs. folate-containing medium, cell viability assays, RT-PCR for RFC mRNA, methotrexate influx as transport activity assay, mathematical biomodeling The Journal of biological chemistry Medium 18499665
2017 Activation of vitamin D receptor (VDR) by calcitriol up-regulates RFC (SLC19A1) mRNA, protein expression, and [3H]-methotrexate transport activity at the blood-brain barrier in human cerebral microvascular endothelial cells (hCMEC/D3) and isolated mouse brain capillaries. VDR-targeting siRNA down-regulates RFC expression, confirming VDR as a direct regulator of SLC19A1. Calcitriol treatment of hCMEC/D3 cells and mouse brain capillaries, [3H]-MTX uptake assay, RT-PCR and Western blot, VDR siRNA knockdown Molecular pharmaceutics Medium 28885847
2020 Nuclear respiratory factor 1 (NRF-1)/PGC-1α signaling regulates RFC (SLC19A1) expression and function at the blood-brain barrier. PQQ (NRF-1 ligand) increases NRF-1 binding to SLC19A1 promoter (shown by ChIP assay) and induces RFC expression and [3H]-MTX transport activity; NRF-1 or PGC-1α siRNA knockdown reduces RFC functional expression. ChIP assay for NRF-1 binding to SLC19A1 promoter, siRNA knockdown of NRF-1/PGC-1α, [3H]-MTX uptake assay, RT-PCR and Western blot, in vivo PQQ treatment in mice FASEB journal Medium 32543769
2016 mTORC1 and mTORC2 are positive regulators of folate uptake in human trophoblasts, acting by controlling the plasma membrane abundance (surface expression) of RFC (SLC19A1) and FR-α without affecting global protein expression. Silencing raptor (mTORC1) or rictor (mTORC2) markedly decreased folate uptake and surface transporter levels. siRNA silencing of raptor/rictor in primary human trophoblasts, folate uptake assays, plasma membrane fractionation and immunoblotting Scientific reports Medium 27562465
2018 SLC19A1 knockdown in human adipocytes perturbs intracellular one-carbon cycle (1CC) metabolism, induces global DNA hypermethylation, and increases expression of proinflammatory genes including CCL2. Methylation at the CCL2 promoter CpG locus (cg12698626) directly regulates CCL2 transcription and secretion, linking SLC19A1 to an epigenetic inflammatory mechanism. siRNA knockdown of SLC19A1 in differentiated human adipocytes, microarray, qPCR, DNA methylation by ELISA and pyrosequencing, luciferase reporter assay, targeted metabolomics, cytokine ELISA The Journal of clinical endocrinology and metabolism Medium 29121255
1998 The human RFC-1 (SLC19A1) gene has multiple promoters (at least two, Promoter 1 upstream of exon 1a and Promoter 2 upstream of exon 1b) that direct expression of alternatively spliced transcripts with 5' end heterogeneity. Promoter 2 (exon 1b) has ~3-fold higher basal activity than Promoter 1 in functional transient transfection assays. Genomic DNA sequencing, primer extension analysis, functional deletion analysis with luciferase reporter gene in transient transfection experiments Gene Medium 9602167
2010 The C. elegans ortholog folt-1 (encoding FOLT-1, the RFC/SLC19A1 ortholog) is required for germline proliferation and somatic function; knockout causes severely diminished germline, reduced spermatogenesis, sterility in hermaphrodites, shortened lifespan, and elongated defecation intervals. No increased germline apoptosis was detected, suggesting defective proliferation rather than increased cell death. Genetic knockout analysis (folt-1(ok1460)), germline microscopy, lifespan assays, mating assays, apoptosis staining in C. elegans BMC developmental biology Medium 20441590
2003 RFC/SLC19A1 (reduced folate carrier) is expressed in placenta, yolk sac, and multiple developing embryonic tissues including neural tube, craniofacial region, limb buds, heart, and early eye; by E12.5 RFC protein becomes restricted to the retinal pigment epithelium. This developmental expression pattern was determined by in situ hybridization and immunolocalization. In situ hybridization, immunolocalization in mouse embryos at multiple developmental stages (E9.0–E12.5) BMC developmental biology Medium 12887734
2011 Chronic ethanol ingestion reduces folate transport across the colonic apical membrane by decreasing both affinity (higher Km) and number of transporter molecules (lower Vmax) for RFC. RFC protein is distributed in lipid rafts of the colonic apical membrane, and chronic alcoholism decreases RFC protein levels specifically in lipid raft fractions. Isolated colon apical membrane vesicle transport assays, Western blotting, Optiprep density gradient floatation to isolate lipid rafts, in vivo rat chronic ethanol feeding model Journal of cellular physiology Medium 21069807
2018 miR-595 suppresses SLC19A1 expression post-transcriptionally by directly binding to the 3'-UTR of SLC19A1 (validated by luciferase reporter assay), reducing RFC1 protein levels, intracellular methotrexate concentrations, and MTX-induced cytotoxicity and apoptosis in CEM/C1 leukemia cells. Luciferase reporter assay with SLC19A1 3'-UTR, miR-595 mimic and inhibitor transfection, Western blotting, intracellular MTX quantification by ELISA, cell viability and apoptosis assays Basic & clinical pharmacology & toxicology Medium 29345051

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 SLC19A1 transports immunoreactive cyclic dinucleotides. Nature 297 31511694
2001 Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. Molecular cell 289 11389843
2004 The PCNA-RFC families of DNA clamps and clamp loaders. Progress in nucleic acid research and molecular biology 271 15210332
2019 SLC19A1 Is an Importer of the Immunotransmitter cGAMP. Molecular cell 269 31126740
1995 Nucleotide excision repair DNA synthesis by DNA polymerase epsilon in the presence of PCNA, RFC, and RPA. Biochemistry 224 7711023
1989 Purification of a cellular replication factor, RF-C, that is required for coordinated synthesis of leading and lagging strands during simian virus 40 DNA replication in vitro. Molecular and cellular biology 204 2565531
1998 Overexpression and topology of the Shigella flexneri O-antigen polymerase (Rfc/Wzy). Molecular microbiology 153 9680210
2003 Elg1 forms an alternative RFC complex important for DNA replication and genome integrity. The EMBO journal 143 12912927
2003 Elg1 forms an alternative PCNA-interacting RFC complex required to maintain genome stability. Current biology : CB 134 13678589
1994 Characterization of the rfc region of Shigella flexneri. Journal of bacteriology 131 7507920
2010 Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response. Nature structural & molecular biology 106 20972444
2010 Elg1, an alternative subunit of the RFC clamp loader, preferentially interacts with SUMOylated PCNA. The EMBO journal 91 20571511
2012 Paradoxical impact of two folate receptors, FRα and RFC, in ovarian cancer: effect on cell proliferation, invasion and clinical outcome. PloS one 89 23144806
2008 Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1. The Journal of biological chemistry 89 18499658
2019 Regulation of PCNA cycling on replicating DNA by RFC and RFC-like complexes. Nature communications 84 31160570
2002 Clamp and clamp loader structures of the human checkpoint protein complexes, Rad9-1-1 and Rad17-RFC. Genes to cells : devoted to molecular & cellular mechanisms 77 12167163
2001 Clamp loader structure predicts the architecture of DNA polymerase III holoenzyme and RFC. Current biology : CB 77 11719243
1992 Calf thymus RF-C as an essential component for DNA polymerase delta and epsilon holoenzymes function. Nucleic acids research 77 1354854
2012 The RFC clamp loader: structure and function. Sub-cellular biochemistry 75 22918590
1999 A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae. Genetics 75 10545450
2017 Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication. Genes 71 28134787
1991 Mutations at rfc or pmi attenuate Salmonella typhimurium virulence for mice. Infection and immunity 63 1997412
1991 Molecular cloning, characterization, and nucleotide sequence of the rfc gene, which encodes an O-antigen polymerase of Salmonella typhimurium. Journal of bacteriology 62 1707412
1995 Molecular cloning and characterization of the rfc gene of Pseudomonas aeruginosa (serotype O5). Molecular microbiology 60 7565115
2012 Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease. Pharmacogenetics and genomics 59 22890010
2009 The Elg1-RFC clamp-loading complex performs a role in sister chromatid cohesion. PloS one 57 19262753
1998 A single amino acid difference within the folate transporter encoded by the murine RFC-1 gene selectively alters its interaction with folate analogues. Implications for intrinsic antifolate resistance and directional orientation of the transporter within the plasma membrane of tumor cells. The Journal of biological chemistry 53 9446553
1998 Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity. The Journal of biological chemistry 51 9488738
2022 Methotrexate recognition by the human reduced folate carrier SLC19A1. Nature 50 36071163
1998 Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promoters and alternatively spliced transcripts with 5' end heterogeneity. Gene 49 9602167
2017 Regulation of Reduced Folate Carrier (RFC) by Vitamin D Receptor at the Blood-Brain Barrier. Molecular pharmaceutics 47 28885847
2015 A conserved Polϵ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1. Nucleic acids research 47 26250113
2006 The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time. The EMBO journal 47 16525505
2018 Removal and biodegradation of different petroleum hydrocarbons using the filamentous fungus Aspergillus sp. RFC-1. MicrobiologyOpen 46 29577679
2010 Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8. The Journal of biological chemistry 45 20826785
2005 Unzipped and loaded: the role of DNA helicases and RFC clamp-loading complexes in sister chromatid cohesion. The Journal of cell biology 44 15955849
2009 Mechanism of ATP-driven PCNA clamp loading by S. cerevisiae RFC. Journal of molecular biology 43 19285992
2009 The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women. Annals of human genetics 43 19650776
2016 Mechanistic target of rapamycin (mTOR) regulates trophoblast folate uptake by modulating the cell surface expression of FR-α and the RFC. Scientific reports 42 27562465
2022 Recognition of cyclic dinucleotides and folates by human SLC19A1. Nature 40 36265513
2020 Ctf18-RFC and DNA Pol ϵ form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication. Nucleic acids research 40 32585006
2023 Robust Spontaneous Raman Flow Cytometry for Single-Cell Metabolic Phenome Profiling via pDEP-DLD-RFC. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 39 36871147
2003 Reduced-folate carrier (RFC) is expressed in placenta and yolk sac, as well as in cells of the developing forebrain, hindbrain, neural tube, craniofacial region, eye, limb buds and heart. BMC developmental biology 39 12887734
2001 Expression of the reduced folate carrier SLC19A1 in IEC-6 cells results in two distinct transport activities. American journal of physiology. Cell physiology 39 11600421
2017 Human CTF18-RFC clamp-loader complexed with non-synthesising DNA polymerase ε efficiently loads the PCNA sliding clamp. Nucleic acids research 38 28199690
2011 New functions of Ctf18-RFC in preserving genome stability outside its role in sister chromatid cohesion. PLoS genetics 38 21347277
2008 The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis. The Journal of biological chemistry 38 18499665
2004 The reconstituted human Chl12-RFC complex functions as a second PCNA loader. Genes to cells : devoted to molecular & cellular mechanisms 38 15066120
2020 Extracellular vesicle-derived circ_SLC19A1 promotes prostate cancer cell growth and invasion through the miR-497/septin 2 pathway. Cell biology international 37 31903637
2017 Structural Basis for the Recruitment of Ctf18-RFC to the Replisome. Structure (London, England : 1993) 37 29225079
2011 A central swivel point in the RFC clamp loader controls PCNA opening and loading on DNA. Journal of molecular biology 37 22197374
2007 Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene could affect rheumatoid arthritis patient response to methotrexate therapy. Rheumatology international 36 17404734
2022 Cryo-EM structures reveal that RFC recognizes both the 3'- and 5'-DNA ends to load PCNA onto gaps for DNA repair. eLife 35 35829698
2008 On the mechanism of loading the PCNA sliding clamp by RFC. Molecular microbiology 35 18312273
1996 Identification of the O antigen polymerase (rfc) gene in Escherichia coli O4 by insertional mutagenesis using a nonpolar chloramphenicol resistance cassette. Journal of bacteriology 35 8550424
2010 Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines. Vaccine 34 20599580
2010 Association of folate receptor (FOLR1, FOLR2, FOLR3) and reduced folate carrier (SLC19A1) genes with meningomyelocele. Birth defects research. Part A, Clinical and molecular teratology 34 20683905
2015 Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR , TYMS, and TCII genes and the efficacy and toxicity of methotrexate treatment in patients with rheumatoid arthritis. Polskie Archiwum Medycyny Wewnetrznej 33 25599563
2011 ATP binding and hydrolysis-driven rate-determining events in the RFC-catalyzed PCNA clamp loading reaction. Journal of molecular biology 33 22197378
2008 Correlation of polymorphism of MTHFRs and RFC-1 genes with neural tube defects in China. Birth defects research. Part A, Clinical and molecular teratology 33 18022874
2018 Adipocyte Expression of SLC19A1 Links DNA Hypermethylation to Adipose Tissue Inflammation and Insulin Resistance. The Journal of clinical endocrinology and metabolism 32 29121255
1993 FoLT PCR: a simple PCR protocol for amplifying DNA directly from whole blood. BioTechniques 32 8431290
2014 Effects of a microRNA binding site polymorphism in SLC19A1 on methotrexate concentrations in Chinese children with acute lymphoblastic leukemia. Medical oncology (Northwood, London, England) 31 24927955
2002 Molecular modeling-based analysis of interactions in the RFC-dependent clamp-loading process. Protein science : a publication of the Protein Society 31 12237462
2001 ATP utilization by yeast replication factor C. IV. RFC ATP-binding mutants show defects in DNA replication, DNA repair, and checkpoint regulation. The Journal of biological chemistry 31 11549622
2022 Structure of the human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp bound to a dsDNA-ssDNA junction. Nucleic acids research 30 35819203
2011 Replication factor C is a more effective proliferating cell nuclear antigen (PCNA) opener than the checkpoint clamp loader, Rad24-RFC. The Journal of biological chemistry 30 22115746
2010 Correlation between polymorphisms of the reduced folate carrier gene (SLC19A1) and survival after pemetrexed-based therapy in non-small cell lung cancer: a North Central Cancer Treatment Group-based exploratory study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 30 20651609
1997 Organization, structure and alternate splicing of the murine RFC-1 gene encoding a folate transporter. Gene 29 9161403
2022 Molecular mechanism of substrate recognition by folate transporter SLC19A1. Cell discovery 28 36575193
2011 Reduced levels of folate transporters (PCFT and RFC) in membrane lipid rafts result in colonic folate malabsorption in chronic alcoholism. Journal of cellular physiology 28 21069807
2013 Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids in health and disease 27 23656756
2009 Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target. Molecular biology of the cell 27 19846659
2018 Regulation of HLTF-mediated PCNA polyubiquitination by RFC and PCNA monoubiquitination levels determines choice of damage tolerance pathway. Nucleic acids research 26 30335157
2013 Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy. Oncology letters 26 23599757
2013 SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer. PloS one 25 24143213
2011 Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins. Cell cycle (Georgetown, Tex.) 25 21869594
2012 Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis patients. Pharmacogenomics 24 23148635
2010 Knockout of the folate transporter folt-1 causes germline and somatic defects in C. elegans. BMC developmental biology 24 20441590
2023 FAN1 removes triplet repeat extrusions via a PCNA- and RFC-dependent mechanism. Proceedings of the National Academy of Sciences of the United States of America 23 37549289
2020 Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate. Frontiers in pediatrics 23 32612964
2005 Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation in the absence of fully functional RFC in fission yeast. Nucleic acids research 23 16040599
2002 Replication factor C from the hyperthermophilic archaeon Pyrococcus abyssi does not need ATP hydrolysis for clamp-loading and contains a functionally conserved RFC PCNA-binding domain. Journal of molecular biology 23 12417194
2024 Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis. Science (New York, N.Y.) 21 39088616
2020 Nuclear respiratory factor 1 (NRF-1) upregulates the expression and function of reduced folate carrier (RFC) at the blood-brain barrier. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 32543769
2018 Biodegradation of n-hexadecane by Aspergillus sp. RFC-1 and its mechanism. Ecotoxicology and environmental safety 21 30142606
2022 A second DNA binding site on RFC facilitates clamp loading at gapped or nicked DNA. eLife 20 35731107
2009 Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome. Disease markers 20 19729796
2016 Association of MTHFR, SLC19A1 Genetic Polymorphism, Serum Folate, Vitamin B12 and Hcy Status with Cognitive Functions in Chinese Adults. Nutrients 19 27783031
2015 Structures of FolT in substrate-bound and substrate-released conformations reveal a gating mechanism for ECF transporters. Nature communications 19 26198469
2006 Overproduction and purification of RFC-related clamp loaders and PCNA-related clamps from Saccharomyces cerevisiae. Methods in enzymology 19 16793392
2017 Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma: Introducing a Haplotype based Approach. Radiology and oncology 17 29333125
2010 Rfc5p regulates alternate RFC complex functions in sister chromatid pairing reactions in budding yeast. Cell cycle (Georgetown, Tex.) 17 20980821
2004 DNA polymerase delta, RFC and PCNA are required for repair synthesis of large looped heteroduplexes in Saccharomyces cerevisiae. Nucleic acids research 17 15576353
2018 MiR-595 Suppresses the Cellular Uptake and Cytotoxic Effects of Methotrexate by Targeting SLC19A1 in CEM/C1 Cells. Basic & clinical pharmacology & toxicology 16 29345051
2016 Conserved interaction of Ctf18-RFC with DNA polymerase ε is critical for maintenance of genome stability in Saccharomyces cerevisiae. Genes to cells : devoted to molecular & cellular mechanisms 16 26987677
2025 The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells. Molecular cell 15 40578346
2017 Structural studies of RFCCtf18 reveal a novel chromatin recruitment role for Dcc1. EMBO reports 15 28188145
2011 Expression of RFC/SLC19A1 is associated with tumor type in bladder cancer patients. PloS one 15 21760912
1995 Cloning and characterization of the gene (rfc) encoding O-antigen polymerase of Pseudomonas aeruginosa PAO1. Gene 15 8566816

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