Biology:Folate transporter 1

Short description: Mammalian protein found in Homo sapiens

Generic protein structure example

Folate transporter 1 is a protein which in humans is encoded by the SLC19A1 gene.

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. SLC19A1 has also been shown to transport the immune second messenger 2'3'-cGAMP.

Clinical significance

Individuals carrying a specific polymorphism of SLC19A1 (c.80GG) have lower levels of folate. 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

Further reading

• "Human reduced folate carrier: translation of basic biology to cancer etiology and therapy". Cancer and Metastasis Reviews 26 (1): 111–28. March 2007. doi:10.1007/s10555-007-9046-2. PMID 17334909. 
• "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. July 1995. doi:10.1074/jbc.270.29.17468. PMID 7615551. 
• "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. September 1995. PMID 7641195. 
• "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. May 1995. doi:10.1006/bbrc.1995.1739. PMID 7763259. 
• "Molecular cloning of the human placental folate transporter". Biochemical and Biophysical Research Communications 206 (2): 681–7. January 1995. doi:10.1006/bbrc.1995.1096. PMID 7826387. 
• "Isolation of a human cDNA that complements a mutant hamster cell defective in methotrexate uptake". The Journal of Biological Chemistry 270 (7): 2987–92. February 1995. doi:10.1074/jbc.270.7.2987. PMID 7852378. 
• "A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells". The Journal of Biological Chemistry 269 (1): 17–20. January 1994. doi:10.1016/S0021-9258(17)42301-5. PMID 8276792. 
• "Human intestinal folate transport: cloning, expression, and distribution of complementary RNA". Gastroenterology 112 (3): 783–91. March 1997. doi:10.1053/gast.1997.v112.pm9041240. PMID 9041240. 
• "Construction of a 2.5-Mb integrated physical and gene map of distal 21q22.3". Genomics 49 (1): 1–13. April 1998. doi:10.1006/geno.1997.5185. PMID 9570943. 
• "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. May 1998. doi:10.1016/S0378-1119(98)00123-1. PMID 9602167. 
• "Structure and organization of the human reduced folate carrier gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1442 (2–3): 389–93. November 1998. doi:10.1016/s0167-4781(98)00168-7. PMID 9804996. 
• "Topological and functional analysis of the human reduced folate carrier by hemagglutinin epitope insertion". The Journal of Biological Chemistry 274 (23): 16269–78. June 1999. doi:10.1074/jbc.274.23.16269. PMID 10347183. 
• "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. May 2000. doi:10.1038/35012518. PMID 10830953. Bibcode: 2000Natur.405..311H. 
• "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. November 2001. PMID 11705857. 
• "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. February 2002. doi:10.1002/ajmg.10195. PMID 11857541. 
• "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. September 2002. doi:10.1074/jbc.M205955200. PMID 12087110. 
• "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. November 2002. doi:10.1042/BJ20020801. PMID 12139489. 
• "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. November 2002. doi:10.1042/BJ20020512. PMID 12144527. 
• "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. August 2002. doi:10.1016/S0005-2736(02)00467-4. PMID 12175915. 
• "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. January 2003. doi:10.1042/BJ20020419. PMID 12227830. 

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