“SLC19A1”的意思、由来-开放百科全书

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 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.

Further reading

{{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 = 111–28 | date = March 2007 | pmid = 17334909 | doi = 10.1007/s10555-007-9046-2 }}

{{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 = 17468–75 | date = July 1995 | pmid = 7615551 | doi = 10.1074/jbc.270.29.17468 }}

{{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 = 3790–4 | date = September 1995 | pmid = 7641195 | doi = }}

{{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 = 874–9 | date = May 1995 | pmid = 7763259 | doi = 10.1006/bbrc.1995.1739 }}

{{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 = 681–7 | 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 = 2987–92 | date = February 1995 | pmid = 7852378 | doi = 10.1074/jbc.270.7.2987 }}

{{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 = }}

{{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 = 783–91 | 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 = 331–41 | date = May 1998 | pmid = 9602167 | doi = 10.1016/S0378-1119(98)00123-1 }}

{{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 | volume = 1442 | issue = 2–3 | pages = 389–93 | 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 = 16269–78 | date = June 1999 | pmid = 10347183 | doi = 10.1074/jbc.274.23.16269 }}

{{cite journal | vauthors = 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 | title = The DNA sequence of human chromosome 21 | journal = Nature | volume = 405 | issue = 6784 | pages = 311–9 | date = May 2000 | pmid = 10830953 | doi = 10.1038/35012518 }}

{{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 = 3416–22 | date = November 2001 | pmid = 11705857 | doi = }}

{{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 }}

{{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 = 33325–33 | date = September 2002 | pmid = 12087110 | doi = 10.1074/jbc.M205955200 }}

{{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 = 741–50 | 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 = 629–40 | 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 | volume = 1564 | issue = 2 | pages = 333–42 | 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 = 31–7 | date = January 2003 | pmid = 12227830 | pmc = 1223057 | doi = 10.1042/BJ20020419 }}

1 : Solute carrier family

Function

Clinical significance

See also

References

Further reading