Folate transporter 1

Mammalian protein found in Homo sapiens

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]
Band	21q22.3	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]
Band	10 C1\|10 39.72 cM	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

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

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

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000173638 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000001436 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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".
^ 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.
^
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.

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.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)

By group

SLC1–10

(1):	high affinity glutamate and neutral amino-acid transporter SLC1A1 2 3 4 5 6 7
(2):	facilitative GLUT transporter SLC2A1 2 3 4 5 6 7 8 9 10 11 12 13 14
(3):	heavy subunits of heterodimeric amino-acid transporters SLC3A1 2
(4):	bicarbonate transporter SLC4A1 2 3 4 5 6 7 8 9 10 11
(5):	sodium glucose cotransporter SLC5A1 2 3 4 5 6 7 8 9 10 11 12
(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
(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
(8):	Na⁺/Ca²⁺ exchanger SLC8A1 SLC8A2 SLC8A3
(9):	Na⁺/H⁺ exchanger SLC9A1 SLC9A2 SLC9A3 SLC9A4 SLC9A5 SLC9A6 SLC9A7 SLC9A8 SLC9A9 SLC9A10 SLC9A11
(10):	sodium bile salt cotransport SLC10A1 SLC10A2 SLC10A3 SLC10A4 SLC10A5 SLC10A6 SLC10A7 10A1 10A2 10A3 10A7

SLC11–20

(11):	proton coupled metal ion transporter SLC11A1 SLC11A2 11A3
(12):	electroneutral cation-Cl cotransporter SLC12A1 SLC12A2 SLC12A3 SLC12A4 SLC12A5 SLC12A6 SLC12A7 SLC12A8 SLC12A9
(13):	human Na⁺-sulfate/carboxylate cotransporter SLC13A1 SLC13A2 SLC13A3 SLC13A4 SLC13A5
(14):	urea transporter SLC14A1 SLC14A2
(15):	proton oligopeptide cotransporter SLC15A1 SLC15A2 SLC15A3 SLC15A4
(16):	monocarboxylate transporter SLC16A1 SLC16A2 SLC16A3 SLC16A4 SLC16A5 SLC16A6 SLC16A7 SLC16A8 SLC16A9 SLC16A10 SLC16A11 SLC16A12 SLC16A13 SLC16A14
(17):	Vesicular glutamate transporter 1 SLC17A1 SLC17A2 SLC17A3 SLC17A4 SLC17A5 SLC17A6 SLC17A7 SLC17A8 SLC17A9
(18):	vesicular monoamine transporter SLC18A1 SLC18A2 SLC18A3
(19):	folate/thiamine transporter SLC19A1 SLC19A2 SLC19A3
(20):	type III Na⁺-phosphate cotransporter SLC20A1 SLC20A2

SLC21–30

(21):	Organic anion-transporting polypeptide 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
(23):	Na+-dependent ascorbic acid transporter SLC23A1 SLC23A2 SLC23A3 SLC23A4
(24):	Na⁺/(Ca²⁺-K⁺) exchanger SLC24A1 SLC24A2 SLC24A3 SLC24A4 SLC24A5 SLC24A6
(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
(26):	multifunctional anion exchanger SLC26A1 SLC26A2 SLC26A3 SLC26A4 SLC26A5 SLC26A6 SLC26A7 SLC26A8 SLC26A9 SLC26A10 SLC26A11
(27):	fatty acid transport proteins SLC27A1 SLC27A2 SLC27A3 SLC27A4 SLC27A5 SLC27A6
(28):	Na⁺-coupled nucleoside transport (SLC28A1 SLC28A2 SLC28A3
(29):	facilitative nucleoside transporter SLC29A1 SLC29A2 SLC29A3 SLC29A4
(30):	zinc efflux SLC30A1 SLC30A2 SLC30A3 SLC30A4 SLC30A5 SLC30A6 SLC30A7 SLC30A8 SLC30A9 SLC30A10

SLC31–40

(31):	copper transporter SLC31A1
(32):	Vesicular glutamate transporter 1 SLC32A1
(33):	Acetyl-CoA transporter SLC33A1
(34):	type II Na⁺-phosphate cotransporter SLC34A1 SLC34A2 SLC34A3
(35):	nucleoside-sugar transporter SLC35A1 SLC35A2 SLC35A3 SLC35A4 SLC35A5 SLC35B1 SLC35B2 SLC35B3 SLC35B4 SLC35C1 SLC35C2 SLC35D1 SLC35D2 SLC35D3 SLC35E1 SLC35E2 SLC35E3 SLC35E4
(36):	proton-coupled amino-acid transporter SLC36A1 SLC36A2 SLC36A3 SLC36A436A2
(37):	sugar-phosphate/phosphate exchanger SLC37A1 SLC37A2 SLC37A3 SLC37A4
(38):	System A & N, sodium-coupled neutral amino-acid transporter SLC38A1 SLC38A2 SLC38A3 SLC38A4 SLC38A5 SLC38A6 SLC38A10
(39):	metal ion transporter SLC39A1 SLC39A2 SLC39A3 SLC39A4 SLC39A5 SLC39A6 SLC39A7 SLC39A8 SLC39A9 SLC39A10 SLC39A11 SLC39A12 SLC39A13 SLC39A14
(40):	basolateral iron transporter SLC40A1

SLC41–48

(41):	Magnesium transporter E SLC41A1 SLC41A2 SLC41A3
(42):	Ammonia transporter RhAG RhBG RhCG
(43):	Na⁺-independent, system-L like amino-acid transporter SLC43A1 SLC43A2 SLC43A3
(44):	Choline-like transporter SLC44A1 SLC44A2 SLC44A3 SLC44A4 SLC44A5
(45):	Putative sugar transporter SLC45A1 SLC45A2 SLC54A3 SLC45A4
(46):	Folate transporter SLC46A1 SLC46A2
(47):	multidrug and toxin extrusion SLC47A1 SLC47A2
(48):	Heme transporter

SLCO1–4
O1A2 O1B1 O1B3 O2B1 O431 O4A1

Ion pumps

Symporter, Cotransporter	Na⁺/K⁺,Cl⁻ Na⁺/P_i3 Na⁺/Cl⁻ Na⁺/glucose Na⁺/I⁻ Cl⁻/K⁺ 4 5
Antiporter (exchanger)	Na⁺/H⁺ Na⁺/Ca²⁺ Na⁺/(Ca²⁺-K⁺) - Cl⁻/HCO⁻ ₃ (Band 3) Cl⁻-formate Cl⁻-oxalate