Folate transporter 1

{{Short description|Mammalian protein found in Homo sapiens}}

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{{Infobox gene}}

Folate transporter 1 is a protein which in humans is encoded by the SLC19A1 gene.{{cite journal | vauthors = Lapenta V, Sossi V, Gosset P, Vayssettes C, Vitali T, Rabatel N, Tassone F, Blouin JL, Scott HS, Antonarakis SE, Créau N, Brahe C | title = Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3 | journal = Genomics | volume = 49 | issue = 1 | pages = 1–13 | date = April 1998 | pmid = 9570943 | doi = 10.1006/geno.1997.5185 }}

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.{{cite web | title = Entrez Gene: SLC19A1 solute carrier family 19 (folate transporter), member 1 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6573 }} SLC19A1 has also been shown to transport the immune second messenger 2'3'-cGAMP.{{cite journal | vauthors = Ritchie C, Cordova A, Hess G, Bassik M, Li L | title = SLC19A1 Is an Importer of the Immunotransmitter cGAMP. | journal = Molecular Cell | volume = 75 | issue = 2 | pages = 372–381.e5 | date = 25 July 2019 | pmid = 31126740 | pmc = 6711396 | doi = 10.1016/j.molcel.2019.05.006 }}

Clinical significance

Individuals carrying a specific polymorphism of SLC19A1 (c.80GG) have lower levels of folate.{{cite journal | vauthors = 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 | title = The reduced folate carrier (SLC19A1) c.80G>A polymorphism is associated with red cell folate concentrations among women | journal = Annals of Human Genetics | volume = 73 | issue = Pt 5 | pages = 484–491 | date = September 2009 | pmid = 19650776 | pmc = 2812009 | doi = 10.1111/j.1469-1809.2009.00529.x }}

  • {{cite web | vauthors = France K | title = Polymorphisms Affecting Red Cell Folate Concentrations in Women could Identify Increased Risk for certain Birth Defects | date = 22 August 2009 | website = PGxNews | url = http://www.pgxnews.org/web/pgx-pharmacogenomics-articles-reviews/40-pgx-pharmacogenomics-article-review/113-polymorphisms-affecting-red-cell-folate-concentrations-in-women-could-identify-increased-risk-for-certain-birth-defects | archive-url = https://web.archive.org/web/20090922073604/http://www.pgxnews.org/web/pgx-pharmacogenomics-articles-reviews/40-pgx-pharmacogenomics-article-review/113-polymorphisms-affecting-red-cell-folate-concentrations-in-women-could-identify-increased-risk-for-certain-birth-defects | archive-date = 2009-09-22 }} 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

References

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Further reading

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  • {{cite journal | vauthors = Matherly LH, Hou Z, Deng Y | title = Human reduced folate carrier: translation of basic biology to cancer etiology and therapy | journal = Cancer Metastasis Reviews | volume = 26 | issue = 1 | pages = 111–128 | date = March 2007 | pmid = 17334909 | doi = 10.1007/s10555-007-9046-2 | s2cid = 26489607 }}
  • {{cite journal | vauthors = Wong SC, Proefke SA, Bhushan A, Matherly LH | title = Isolation of human cDNAs that restore methotrexate sensitivity and reduced folate carrier activity in methotrexate transport-defective Chinese hamster ovary cells | journal = The Journal of Biological Chemistry | volume = 270 | issue = 29 | pages = 17468–17475 | date = July 1995 | pmid = 7615551 | doi = 10.1074/jbc.270.29.17468 | doi-access = free }}
  • {{cite journal | vauthors = Moscow JA, Gong M, He R, Sgagias MK, Dixon KH, Anzick SL, Meltzer PS, Cowan KH | title = 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 | journal = Cancer Research | volume = 55 | issue = 17 | pages = 3790–3794 | date = September 1995 | pmid = 7641195 }}
  • {{cite journal | vauthors = Yang-Feng TL, Ma YY, Liang R, Prasad PD, Leibach FH, Ganapathy V | title = Assignment of the human folate transporter gene to chromosome 21q22.3 by somatic cell hybrid analysis and in situ hybridization | journal = Biochemical and Biophysical Research Communications | volume = 210 | issue = 3 | pages = 874–879 | date = May 1995 | pmid = 7763259 | doi = 10.1006/bbrc.1995.1739 | doi-access = free }}
  • {{cite journal | vauthors = Prasad PD, Ramamoorthy S, Leibach FH, Ganapathy V | title = Molecular cloning of the human placental folate transporter | journal = Biochemical and Biophysical Research Communications | volume = 206 | issue = 2 | pages = 681–687 | date = January 1995 | pmid = 7826387 | doi = 10.1006/bbrc.1995.1096 }}
  • {{cite journal | vauthors = Williams FM, Flintoff WF | title = Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake | journal = The Journal of Biological Chemistry | volume = 270 | issue = 7 | pages = 2987–2992 | date = February 1995 | pmid = 7852378 | doi = 10.1074/jbc.270.7.2987 | doi-access = free }}
  • {{cite journal | vauthors = Dixon KH, Lanpher BC, Chiu J, Kelley K, Cowan KH | title = A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells | journal = The Journal of Biological Chemistry | volume = 269 | issue = 1 | pages = 17–20 | date = January 1994 | pmid = 8276792 | doi = 10.1016/S0021-9258(17)42301-5 | doi-access = free }}
  • {{cite journal | vauthors = Nguyen TT, Dyer DL, Dunning DD, Rubin SA, Grant KE, Said HM | title = Human intestinal folate transport: cloning, expression, and distribution of complementary RNA | journal = Gastroenterology | volume = 112 | issue = 3 | pages = 783–791 | date = March 1997 | pmid = 9041240 | doi = 10.1053/gast.1997.v112.pm9041240 }}
  • {{cite journal | vauthors = Lapenta V, Sossi V, Gosset P, Vayssettes C, Vitali T, Rabatel N, Tassone F, Blouin JL, Scott HS, Antonarakis SE, Créau N, Brahe C | title = Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3 | journal = Genomics | volume = 49 | issue = 1 | pages = 1–13 | date = April 1998 | pmid = 9570943 | doi = 10.1006/geno.1997.5185 }}
  • {{cite journal | vauthors = Tolner B, Roy K, Sirotnak FM | title = Structural analysis of the human RFC-1 gene encoding a folate transporter reveals multiple promoters and alternatively spliced transcripts with 5' end heterogeneity | journal = Gene | volume = 211 | issue = 2 | pages = 331–341 | date = May 1998 | pmid = 9602167 | doi = 10.1016/S0378-1119(98)00123-1 | doi-access = free }}
  • {{cite journal | vauthors = Zhang L, Wong SC, Matherly LH | title = Structure and organization of the human reduced folate carrier gene | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1442 | issue = 2–3 | pages = 389–393 | date = November 1998 | pmid = 9804996 | doi = 10.1016/s0167-4781(98)00168-7 }}
  • {{cite journal | vauthors = Ferguson PL, Flintoff WF | title = Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion | journal = The Journal of Biological Chemistry | volume = 274 | issue = 23 | pages = 16269–16278 | date = June 1999 | pmid = 10347183 | doi = 10.1074/jbc.274.23.16269 | doi-access = free }}
  • {{cite journal | vauthors = Whetstine JR, Gifford AJ, Witt T, Liu XY, Flatley RM, Norris M, Haber M, Taub JW, Ravindranath Y, Matherly LH | title = 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 | journal = Clinical Cancer Research| volume = 7 | issue = 11 | pages = 3416–3422 | date = November 2001 | pmid = 11705857 }}
  • {{cite journal | vauthors = Shaw GM, Lammer EJ, Zhu H, Baker MW, Neri E, Finnell RH | title = Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida | journal = American Journal of Medical Genetics | volume = 108 | issue = 1 | pages = 1–6 | date = February 2002 | pmid = 11857541 | doi = 10.1002/ajmg.10195 | doi-access = free }}
  • {{cite journal | vauthors = Marchant JS, Subramanian VS, Parker I, Said HM | title = Intracellular trafficking and membrane targeting mechanisms of the human reduced folate carrier in Mammalian epithelial cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 36 | pages = 33325–33333 | date = September 2002 | pmid = 12087110 | doi = 10.1074/jbc.M205955200 | doi-access = free }}
  • {{cite journal | vauthors = Rothem L, Ifergan I, Kaufman Y, Priest DG, Jansen G, Assaraf YG | title = 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 | journal = The Biochemical Journal | volume = 367 | issue = Pt 3 | pages = 741–750 | date = November 2002 | pmid = 12139489 | pmc = 1222927 | doi = 10.1042/BJ20020801 }}
  • {{cite journal | vauthors = Whetstine JR, Flatley RM, Matherly LH | title = 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 | journal = The Biochemical Journal | volume = 367 | issue = Pt 3 | pages = 629–640 | date = November 2002 | pmid = 12144527 | pmc = 1222932 | doi = 10.1042/BJ20020512 }}
  • {{cite journal | vauthors = Liu XY, Matherly LH | title = Analysis of membrane topology of the human reduced folate carrier protein by hemagglutinin epitope insertion and scanning glycosylation insertion mutagenesis | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1564 | issue = 2 | pages = 333–342 | date = August 2002 | pmid = 12175915 | doi = 10.1016/S0005-2736(02)00467-4 }}
  • {{cite journal | vauthors = Liu XY, Witt TL, Matherly LH | title = 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 | journal = The Biochemical Journal | volume = 369 | issue = Pt 1 | pages = 31–37 | date = January 2003 | pmid = 12227830 | pmc = 1223057 | doi = 10.1042/BJ20020419 }}

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{{NLM content}}

{{Membrane transport proteins}}

Category:Solute carrier family