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edit Solute carrier family 19 (folate transporter), member 1 Identifiers Symbols SLC19A1; RFC1; CHMD; FOLT; IFC1; REFC External IDs OMIM: 600424 MGI: 103182 HomoloGene: 57139 GeneCards: SLC19A1 Gene Gene Ontology Molecular function • folic acid binding • folic acid transporter activity • reduced folate carrier activity • methotrexate transporter activity Cellular component • membrane fraction • integral to plasma membrane • membrane Biological process • transport • folic acid transport Sources: Amigo / QuickGO RNA expression pattern More reference expression data Orthologs Species Human Mouse Entrez 6573 20509 Ensembl ENSG00000173638 ENSMUSG00000001436 UniProt P41440 Q542F3 RefSeq (mRNA) NM_003056 NM_031196 RefSeq (protein) NP_003047 NP_112473 Location (UCSC) Chr 21: 45.74 - 45.79 Mb Chr 10: 76.48 - 76.49 Mb PubMed search [1] [2] Solute carrier family 19 (folate transporter), member 1, also known as SLC19A1 or RFC1, is a protein which in humans is encoded by the SLC19A1 gene.[1] Contents 1 Function 2 Clinical significance 3 See also 4 References 5 Further reading Function Transport of folate compounds into mammalian cells can occur via receptor-mediated (see folate receptor 1) or carrier-mediated mechanisms. A functional coordination between these 2 mechanisms has been proposed to be the method of folate uptake in certain cell types. Methotrexate (MTX) is an antifolate chemotherapeutic agent that is actively transported by the carrier-mediated uptake system. RFC1 plays a role in maintaining intracellular concentrations of folate.[2] Clinical significance Individuals carrying a specific polymorphism of SLC19A1 (c.80GG) have lower levels of folate.[3] Other studies have also shown that individuals carrying the c.80AA polymrophism who are treated with methotrexate have higher levels of this anti-folate chemotherapeutic agent. Personalized dosing of the drug depending on the patient's genotype may therefore be required. See also Solute carrier family References ^ Lapenta V, Sossi V, Gosset P, Vayssettes C, Vitali T, Rabatel N, Tassone F, Blouin JL, Scott HS, Antonarakis SE, Créau N, Brahe C (April 1998). "Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3". Genomics 49 (1): 1–13. doi:10.1006/geno.1997.5185. PMID 9570943.  ^ "Entrez Gene: SLC19A1 solute carrier family 19 (folate transporter), member 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6573.  ^ Stanisławska-Sachadyn A, Mitchell LE, Woodside JV, Buckley PT, Kealey C, Young IS, Scott JM, Murray L, Boreham CA, McNulty H, Strain JJ, Whitehead AS (September 2009). "The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women". Ann. Hum. Genet. 73 (Pt 5): 484–91. doi:10.1111/j.1469-1809.2009.00529.x. PMC 2812009. PMID 19650776. Lay summary – PGxNews.Org.  Further reading Matherly LH, Hou Z, Deng Y (2007). "Human reduced folate carrier: translation of basic biology to cancer etiology and therapy.". Cancer Metastasis Rev. 26 (1): 111–28. doi:10.1007/s10555-007-9046-2. PMID 17334909.  Wong SC, Proefke SA, Bhushan A, Matherly LH (1995). "Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells.". J. Biol. Chem. 270 (29): 17468–75. doi:10.1074/jbc.270.29.17468. PMID 7615551.  Moscow JA, Gong M, He R, et al. (1995). "Isolation of a gene encoding a human reduced folate carrier (RFC1) and analysis of its expression in transport-deficient, methotrexate-resistant human breast cancer cells.". Cancer Res. 55 (17): 3790–4. PMID 7641195.  Yang-Feng TL, Ma YY, Liang R, et al. (1995). "Assignment of the human folate transporter gene to chromosome 21q22.3 by somatic cell hybrid analysis and in situ hybridization.". Biochem. Biophys. Res. Commun. 210 (3): 874–9. doi:10.1006/bbrc.1995.1739. PMID 7763259.  Prasad PD, Ramamoorthy S, Leibach FH, Ganapathy V (1995). "Molecular cloning of the human placental folate transporter.". Biochem. Biophys. Res. Commun. 206 (2): 681–7. doi:10.1006/bbrc.1995.1096. PMID 7826387.  Williams FM, Flintoff WF (1995). "Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake.". J. Biol. Chem. 270 (7): 2987–92. doi:10.1074/jbc.270.7.2987. PMID 7852378.  Dixon KH, Lanpher BC, Chiu J, et al. (1994). "A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells.". J. Biol. Chem. 269 (1): 17–20. PMID 8276792.  Nguyen TT, Dyer DL, Dunning DD, et al. (1997). "Human intestinal folate transport: cloning, expression, and distribution of complementary RNA.". Gastroenterology 112 (3): 783–91. doi:10.1053/gast.1997.v112.pm9041240. PMID 9041240.  Lapenta V, Sossi V, Gosset P, et al. (1998). "Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3.". Genomics 49 (1): 1–13. doi:10.1006/geno.1997.5185. PMID 9570943.  Tolner B, Roy K, Sirotnak FM (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 211 (2): 331–41. doi:10.1016/S0378-1119(98)00123-1. PMID 9602167.  Zhang L, Wong SC, Matherly LH (1998). "Structure and organization of the human reduced folate carrier gene.". Biochim. Biophys. Acta 1442 (2-3): 389–93. PMID 9804996.  Ferguson PL, Flintoff WF (1999). "Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion.". J. Biol. Chem. 274 (23): 16269–78. doi:10.1074/jbc.274.23.16269. PMID 10347183.  Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.  Whetstine JR, Gifford AJ, Witt T, et al. (2002). "Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers.". Clin. Cancer Res. 7 (11): 3416–22. PMID 11705857.  Shaw GM, Lammer EJ, Zhu H, et al. (2002). "Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida.". Am. J. Med. Genet. 108 (1): 1–6. doi:10.1002/ajmg.10195. PMID 11857541.  Marchant JS, Subramanian VS, Parker I, Said HM (2002). "Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in Mammalian epithelial cells.". J. Biol. Chem. 277 (36): 33325–33. doi:10.1074/jbc.M205955200. PMID 12087110.  Rothem L, Ifergan I, Kaufman Y, et al. (2002). "Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines.". Biochem. J. 367 (Pt 3): 741–50. doi:10.1042/BJ20020801. PMC 1222927. PMID 12139489.  Whetstine JR, Flatley RM, Matherly LH (2002). "The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter.". Biochem. J. 367 (Pt 3): 629–40. doi:10.1042/BJ20020512. PMC 1222932. PMID 12144527.  Liu XY, Matherly LH (2002). "Analysis of membrane topology of the human reduced folate carrier protein by hemagglutinin epitope insertion and scanning glycosylation insertion mutagenesis.". Biochim. Biophys. Acta 1564 (2): 333–42. doi:10.1016/S0005-2736(02)00467-4. PMID 12175915.  Liu XY, Witt TL, Matherly LH (2003). "Restoration of high-level transport activity by human reduced folate carrier/ThTr1 thiamine transporter chimaeras: role of the transmembrane domain 6/7 linker region in reduced folate carrier function.". Biochem. J. 369 (Pt 1): 31–7. doi:10.1042/BJ20020419. PMC 1223057. PMID 12227830.  This membrane protein-related article is a stub. You can help Wikipedia by expanding it.v · d · e This article incorporates text from the United States National Library of Medicine, which is in the public domain. v · d · eMembrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A) By group 1-10 (1) high affinity glutamate and neutral amino-acid transporter (SLC1A1, SLC1A2, SLC1A3, SLC1A4, SLC1A5, SLC1A6, SLC1A7); 1A1-7 · 1A1 · 1A2 · 1A3 · 1A4 · 1A5 · 1A6 · 1A7 (2) facilitative GLUT transporter (SLC2A1, SLC2A2, SLC2A3, SLC2A4, SLC2A5, SLC2A6, SLC2A7, SLC2A8, SLC2A9, SLC2A10, SLC2A11, SLC2A12, SLC2A13, SLC2A14); Glucose transporter: 2A1 (GLUT1) · 2A2 (GLUT2) · 2A3 (GLUT3) · 2A4 (GLUT4) · 2A5 (GLUT5) · 2A6 (GLUT6) · 2A7 (GLUT7) · 2A8 (GLUT8) · 2A9 · 2A10 · 2A12 (3) heavy subunits of heterodimeric amino-acid transporters (SLC3A1, SLC3A2); AA (3A1 · 3A2) · (4) bicarbonate transporter (SLC4A1, SLC4A2, SLC4A3, SLC4A4, SLC4A5, SLC4A6, SLC4A7, SLC4A8, SLC4A9, SLC4A10, SLC4A11); 4A1 · 4A2 · 4A3 · 4A4 · 4A5 · 4A7 · 4A8 · 4A11 · (5) sodium glucose cotransporter (SLC5A1, SLC5A2, SLC5A3, SLC5A4, SLC5A5, SLC5A6, SLC5A7, SLC5A8, SLC5A9, SLC5A10, SLC5A11, SLC5A12); 5A1-2 · 5A1 · 5A3 · 5A4 · 5A5 · 5A8 · (6) sodium- and chloride- dependent sodium:neurotransmitter symporters (SLC6A1, SLC6A2, SLC6A3, SLC6A4, SLC6A5, SLC6A6, SLC6A7, SLC6A8, SLC6A9, SLC6A10, SLC6A11, SLC6A12, SLC6A13, SLC6A14, SLC6A15, SLC6A16, SLC6A17, SLC6A18, SLC6A19, SLC6A20); 6A1 · 6A2 · 6A3 · 6A4 · 6A5 · 6A8 · 6A9 · 6A18 · 6A19 · 6A20 · (7) cationic amino-acid transporter/glycoprotein-associated (SLC7A1, SLC7A2, SLC7A3, SLC7A4) glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A9, SLC7A10, SLC7A11, SLC7A13, SLC7A14); 7A1 · 7A2 · 7A3 · 7A4 · AA (7A5 · 7A6 · 7A7 · 7A8) · 7A9 · 7A10 · 7A11 · (8) Na+/Ca2+ exchanger (SLC8A1, SLC8A2, SLC8A3); 8A1-3 · (9) Na+/H+ exchanger (SLC9A1, SLC9A2, SLC9A3, SLC9A4, SLC9A5, SLC9A6, SLC9A7, SLC9A8, SLC9A9, SLC9A10, SLC9A11); 9A1 · 9A2 · 9A3 · 9A3R1 · 9A3R2 · 9A5 · 9A6 · 9A8 · 9A10 · 9A11 · (10) sodium bile salt cotransport (SLC10A1, SLC10A2, SLC10A3, SLC10A4, SLC10A5, SLC10A6, SLC10A7); 10A1 · 10A2 · 10A3 · 10A7 11-20 (11) proton coupled metal ion transporter (SLC11A1, SLC11A2); 11A1 · 11A2 · 11A3 · (12) electroneutral cation-Cl cotransporter (SLC12A1, SLC12A1, SLC12A2, SLC12A3, SLC12A4, SLC12A5, SLC12A6, SLC12A7, SLC12A8, SLC12A9); 12A1-2 · 12A3 · 12A4 · 12A5 · 12A6 · 12A7 · (13) human Na+-sulfate/carboxylate cotransporter (SLC13A1, SLC13A2, SLC13A3, SLC13A4, SLC13A5); 13A3 · (14) urea transporter (SLC14A1, SLC14A2); 14A1 · 14A2 · (15) proton oligopeptide cotransporter (SLC15A1, SLC15A2, SLC15A3, SLC15A4); 15A1 · 15A2 · (16) monocarboxylate transporter (SLC16A1, SLC16A2, SLC16A3, SLC16A4, SLC16A5, SLC16A6, SLC16A7, SLC16A8, SLC16A9, SLC16A10, SLC16A11, SLC16A12, SLC16A13, SLC16A14); 16A1 · 16A2 · 16A3 · 16A4 · (17) vesicular glutamate transporter (SLC17A1, SLC17A2, SLC17A3, SLC17A4, SLC17A5, SLC17A6, SLC17A7, SLC17A8, SLC17A9); 17A1 · 17A5 · 17A6-8 · 17A7 · (18) vesicular amine transporter (SLC18A1, SLC18A2, SLC18A3); 18A1 · 18A2 · 18A3 · (19) folate/thiamine transporter (SLC19A1, SLC19A2, SLC19A3); 19A1 · 19A2 · 19A3 · (20) type III Na+-phosphate cotransporter (SLC20A1, SLC20A2); 20A1 · 20A2 21-30 (21) organic anion transporting (SLCO1A2, SLCO1B1, SLCO1B3, SLCO1B4, SLCO1C1) (SLCO2A1, SLCO2B1) (SLCO3A1) (SLCO4A1, SLCO4C1) (SLCO5A1) (SLCO6A1) (22) organic cation/anion/zwitterion transporter (SLC22A1, SLC22A2, SLC22A3, SLC22A4, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLC22A9, SLC22A10, SLC22A11, SLC22A12, SLC22A13, SLC22A14, SLC22A15, SLC22A16, SLC22A17, SLC22A18, SLC22A19, SLC22A20); 22A1 · 22A2 · 22A3 · 22A4 · 22A5 · 22A6 · 22A7 · 22A9 · 22A10 · 22A11 · 22A12 · 22A18 · 22A25 · (23) Na+-dependent ascorbic acid transporter (SLC23A1, SLC23A2, SLC23A3, SLC23A4); 23A1 · 23A2 · (24) Na+/(Ca2+-K+) exchanger (SLC24A1, SLC24A2, SLC24A3, SLC24A4, SLC24A5, SLC24A6); 24A1-2 · 24A5 · (25) mitochondrial carrier (SLC25A1, SLC25A2, SLC25A3, SLC25A4, SLC25A5, SLC25A6, SLC25A7, SLC25A8, SLC25A9, SLC25A10, SLC25A11, SLC25A12, SLC25A13, SLC25A14, SLC25A15, SLC25A16, SLC25A17, SLC25A18, SLC25A19, SLC25A20, SLC25A21, SLC25A22, SLC25A23, SLC25A24, SLC25A25, SLC25A26, SLC25A27, SLC25A28, SLC25A29, SLC25A30, SLC25A31, SLC25A32, SLC25A33, SLC25A34, SLC25A35, SLC25A36, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, SLC25A46); Mitochondrial carrier: 25A1 · 25A3 · 25A4-6 (25A4, 25A6), 25A8 · 25A10 · 25A11 · 25A12 · 25A13 · 25A14 · 25A15 · 25A17 · 25A19 · 25A20 · 25A27 · 25A31 · 25A37 · 25A38 · 25A39 (26) multifunctional anion exchanger (SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A5, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A10, SLC26A11); 26A2 · 26A3 · 26A4 · 26A5 · 26A6 · 26A7 · 26A8 · (27) fatty acid transport proteins (SLC27A1, SLC27A2, SLC27A3, SLC27A4, SLC27A5, SLC27A6); 27A1 · 27A2 · 27A3 · 27A4 · (28) Na+-coupled nucleoside transport (SLC28A1, SLC28A2, SLC28A3); 28A1 · 28A2 · (29) facilitative nucleoside transporter (SLC29A1, SLC29A2, SLC29A3, SLC29A4); 29A1 · 29A2 · 29A4 · (30) zinc efflux (SLC30A1, SLC30A2, SLC30A3, SLC30A4, SLC30A5, SLC30A6, SLC30A7, SLC30A8, SLC30A9, SLC30A10); 30A1 · 30A4 · 30A7 · 30A8 31-40 (31) copper transporter (SLC31A1); 31A1 · 31A2 · (32) vesicular inhibitory amino-acid transporter (SLC32A1); 32A1 · (33) Acetyl-CoA transporter (SLC33A1) (34) type II Na+-phosphate cotransporter (SLC34A1, SLC34A2, SLC34A3); 34A1 · 34A2 · 34A3 · (35) nucleoside-sugar transporter (SLC35A1, SLC35A2, SLC35A3, SLC35A4, SLC35A5) (SLC35B1, SLC35B2, SLC35B3, SLC35B4) (SLC35C1, SLC35C2) (SLC35D1, SLC35D2, SLC35D3) (SLC35E1, SLC35E2, SLC35E3, SLC35E4); 35A1 · 35A2 · 35B2 · 35B4 · 35C1 (36) proton-coupled amino-acid transporter (SLC36A1, SLC36A2, SLC36A3, SLC36A4);  · 36A1 · 36A2 · (37) sugar-phosphate/phosphate exchanger (SLC37A1, SLC37A2, SLC37A3, SLC37A4); 37A4 · (38) System A & N, sodium-coupled neutral amino-acid transporter (SLC38A1, SLC38A2, SLC38A3, SLC38A4, SLC38A5, SLC38A6); 38A2 · 38A3 · (39) metal ion transporter (SLC39A1, SLC39A2, SLC39A3, SLC39A4, SLC39A5, SLC39A6, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A11, SLC39A12, SLC39A13, SLC39A14); 39A1 · 39A2 · 39A3 · 39A4 · 39A6 · 39A7 · 39A10 (40) basolateral iron transporter (SLC40A1); 40A1 · 41-48 (41) MgtE-like magnesium transporter (SLC41A1, SLC41A2, SLC41A3) (42) Rh ammonium transporter (RhAG, RhBG, RhCG); 42A1 · 42A2 · 42A3 · (43) Na+-independent, system-L like amino-acid transporter (SLC43A1, SLC43A2, SLC43A3); 43A1 · (44) Choline-like transporter (SLC44A1, SLC44A2, SLC44A3, SLC44A4, SLC44A5); 44A1 · 44A2 · 44A4 · (45) Putative sugar transporter (SLC45A1, SLC45A2, SLC54A3, SLC45A4); 45A2 · 45A3 · (46) Folate transporter (SLC46A1, SLC46A2); 46A1 · (47) multidrug and toxin extrusion (SLC47A1, SLC47A2); MATE (47A1 · 47A2) (48) Heme transporter O O1A2 · O1B1 · O1B3 · O2B1 · O431 · O4A1 Ion pumps Symporter, Cotransporter Na+/K+/2Cl- - Na/Pi3 - Na+/Cl- - Na/glucose - Na+/I- - Cl-/K+ (4, 5) Antiporter (exchanger) Na+/H+ - Na+/Ca2+ (Na+/(Ca2+-K+)) - Cl-/HCO3- (Band 3) - Cl-formate exchanger - Cl-oxalate exchanger see also solute carrier disorders B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr