Folate transporter 1

Folate transporter 1 is a protein which in humans is encoded by the SLC19A1 gene.^[5]

SLC19A1
Identifiers
Aliases	SLC19A1, CHMD, FOLT, IFC1, REFC, RFC1, solute carrier family 19 member 1, IFC-1, RFC, hRFC, RFT-1, hMEGAF
External IDs	OMIM: 600424; MGI: 103182; HomoloGene: 57139; GeneCards: SLC19A1; OMA:SLC19A1 - orthologs
Gene location (Human) Chr. Chromosome 21 (human)[1] Band 21q22.3 Start 45,493,572 bp[1] End 45,573,365 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 39.72 cM Start 77,032,241 bp[2] End 77,061,002 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa blood endothelial cell Epithelium of choroid plexus retinal pigment epithelium duodenum gallbladder stromal cell of endometrium right lung putamen Top expressed in Paneth cell right kidney retinal pigment epithelium vestibular membrane of cochlear duct choroid plexus of fourth ventricle ciliary body Epithelium of choroid plexus human kidney crypt of lieberkuhn of small intestine endothelial cell of lymphatic vessel More reference expression data BioGPS More reference expression data
Gene ontology Molecular function folic acid binding methotrexate transmembrane transporter activity vitamin transmembrane transporter activity folic acid transmembrane transporter activity folate:anion antiporter activity Cellular component integral component of membrane integral component of plasma membrane apical plasma membrane membrane basolateral plasma membrane plasma membrane Biological process folic acid metabolic process folate transmembrane transport folic acid transport methotrexate transport vitamin transport folate import across plasma membrane transmembrane transport vitamin transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6573 20509 Ensembl ENSG00000173638 ENSMUSG00000001436 UniProt P41440 P41438 RefSeq (mRNA) NM_001205206 NM_001205207 NM_003056 NM_194255 NM_001352510 NM_001352511 NM_001352512 NM_001199271 NM_031196 RefSeq (protein) NP_001192135 NP_001192136 NP_919231 NP_001339439 NP_001339440 NP_001339441 NP_001186200 NP_112473 Location (UCSC) Chr 21: 45.49 – 45.57 Mb Chr 10: 77.03 – 77.06 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[6] SLC19A1 has also been shown to transport the immune second messenger 2'3'-cGAMP.^[7]

Clinical significance

Individuals carrying a specific polymorphism of SLC19A1 (c.80GG) have lower levels of folate.^[8] Other studies have also shown that individuals carrying the c.80AA polymorphism 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.

Alternative names

• Reduced folate carrier 1
• Intestinal folate carrier 1

See also

• Solute carrier family
• Folate-binding protein
• Reduced folate carrier family

References

1. GRCh38: Ensembl release 89: ENSG00000173638 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000001436 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. "Entrez Gene: SLC19A1 solute carrier family 19 (folate transporter), member 1".
7. Ritchie, C; Cordova, AF; Hess, GT; Bassik, MC; Li, L (25 July 2019). "SLC19A1 Is an Importer of the Immunotransmitter cGAMP". Molecular Cell. 75 (2): 372–381.e5. doi:10.1016/j.molcel.2019.05.006. PMC 6711396. PMID 31126740.
8. 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". Annals of Human Genetics. 73 (Pt 5): 484–91. doi:10.1111/j.1469-1809.2009.00529.x. PMC 2812009. PMID 19650776.

   • Kelly France (22 August 2009). "Polymorphisms Affecting Red Cell Folate Concentrations in Women could Identify Increased Risk for certain Birth Defects". PGxNews. Archived from the original on 2009-09-22.

Further reading

• Matherly LH, Hou Z, Deng Y (March 2007). "Human reduced folate carrier: translation of basic biology to cancer etiology and therapy". Cancer and Metastasis Reviews. 26 (1): 111–28. doi:10.1007/s10555-007-9046-2. PMID 17334909. S2CID 26489607.
• Wong SC, Proefke SA, Bhushan A, Matherly LH (July 1995). "Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells". The Journal of Biological Chemistry. 270 (29): 17468–75. doi:10.1074/jbc.270.29.17468. PMID 7615551.
• Moscow JA, Gong M, He R, Sgagias MK, Dixon KH, Anzick SL, Meltzer PS, Cowan KH (September 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 Research. 55 (17): 3790–4. PMID 7641195.
• Yang-Feng TL, Ma YY, Liang R, Prasad PD, Leibach FH, Ganapathy V (May 1995). "Assignment of the human folate transporter gene to chromosome 21q22.3 by somatic cell hybrid analysis and in situ hybridization". Biochemical and Biophysical Research Communications. 210 (3): 874–9. doi:10.1006/bbrc.1995.1739. PMID 7763259.
• Prasad PD, Ramamoorthy S, Leibach FH, Ganapathy V (January 1995). "Molecular cloning of the human placental folate transporter". Biochemical and Biophysical Research Communications. 206 (2): 681–7. doi:10.1006/bbrc.1995.1096. PMID 7826387.
• Williams FM, Flintoff WF (February 1995). "Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake". The Journal of Biological Chemistry. 270 (7): 2987–92. doi:10.1074/jbc.270.7.2987. PMID 7852378.
• Dixon KH, Lanpher BC, Chiu J, Kelley K, Cowan KH (January 1994). "A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells". The Journal of Biological Chemistry. 269 (1): 17–20. doi:10.1016/S0021-9258(17)42301-5. PMID 8276792.
• Nguyen TT, Dyer DL, Dunning DD, Rubin SA, Grant KE, Said HM (March 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, 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.
• Tolner B, Roy K, Sirotnak FM (May 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 (November 1998). "Structure and organization of the human reduced folate carrier gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1442 (2–3): 389–93. doi:10.1016/s0167-4781(98)00168-7. PMID 9804996.
• Ferguson PL, Flintoff WF (June 1999). "Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion". The Journal of Biological Chemistry. 274 (23): 16269–78. doi:10.1074/jbc.274.23.16269. PMID 10347183.
• Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
• Whetstine JR, Gifford AJ, Witt T, Liu XY, Flatley RM, Norris M, Haber M, Taub JW, Ravindranath Y, Matherly LH (November 2001). "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". Clinical Cancer Research. 7 (11): 3416–22. PMID 11705857.
• Shaw GM, Lammer EJ, Zhu H, Baker MW, Neri E, Finnell RH (February 2002). "Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida". American Journal of Medical Genetics. 108 (1): 1–6. doi:10.1002/ajmg.10195. PMID 11857541.
• Marchant JS, Subramanian VS, Parker I, Said HM (September 2002). "Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in Mammalian epithelial cells". The Journal of Biological Chemistry. 277 (36): 33325–33. doi:10.1074/jbc.M205955200. PMID 12087110.
• Rothem L, Ifergan I, Kaufman Y, Priest DG, Jansen G, Assaraf YG (November 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". The Biochemical Journal. 367 (Pt 3): 741–50. doi:10.1042/BJ20020801. PMC 1222927. PMID 12139489.
• Whetstine JR, Flatley RM, Matherly LH (November 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". The Biochemical Journal. 367 (Pt 3): 629–40. doi:10.1042/BJ20020512. PMC 1222932. PMID 12144527.
• Liu XY, Matherly LH (August 2002). "Analysis of membrane topology of the human reduced folate carrier protein by hemagglutinin epitope insertion and scanning glycosylation insertion mutagenesis". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1564 (2): 333–42. doi:10.1016/S0005-2736(02)00467-4. PMID 12175915.
• Liu XY, Witt TL, Matherly LH (January 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". The Biochemical Journal. 369 (Pt 1): 31–7. doi:10.1042/BJ20020419. PMC 1223057. PMID 12227830.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.