Folylpolyglutamate synthase, mitochondrial is an enzyme that in humans is encoded by the FPGSgene.[1]
This gene encodes the folylpolyglutamate synthetase enzyme. This enzyme has a central role in establishing and maintaining both cytosolic and mitochondrial folylpolyglutamate concentrations and, therefore, is essential for folate homeostasis and the survival of proliferating cells. This enzyme catalyzes the ATP-dependent addition of glutamate moieties to folate and folate derivatives. While several transcript variants may exist for this gene, the full-length natures of only two have been biologically validated to date. These two variants encode distinct isoforms.[1]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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Jones C, Kao FT, Taylor RT (1981). "Chromosomal assignment of the gene for folylpolyglutamate synthetase to human chromosome 9". Cytogenet. Cell Genet. 28 (3): 181–94. doi:10.1159/000131529. PMID6934068.
Freemantle SJ, Taylor SM, Krystal G, Moran RG (1995). "Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene". J. Biol. Chem. 270 (16): 9579–84. doi:10.1074/jbc.270.16.9579. PMID7721888.
Taylor SM, Freemantle SJ, Moran RG (1996). "Structural organization of the human folypoly-gamma-glutamate synthetase gene: evidence for a single genomic locus". Cancer Res. 55 (24): 6030–4. PMID8521387.
Chen L, Qi H, Korenberg J, et al. (1996). "Purification and properties of human cytosolic folylpoly-gamma-glutamate synthetase and organization, localization, and differential splicing of its gene". J. Biol. Chem. 271 (22): 13077–87. doi:10.1074/jbc.271.22.13077. PMID8662720.
Freemantle SJ, Moran RG (1997). "Transcription of the human folylpoly-gamma-glutamate synthetase gene". J. Biol. Chem. 272 (40): 25373–9. doi:10.1074/jbc.272.40.25373. PMID9312158.
McGuire JJ, Russell CA, Balinska M (2000). "Human cytosolic and mitochondrial folylpolyglutamate synthetase are electrophoretically distinct. Expression in antifolate-sensitive and -resistant human cell lines". J. Biol. Chem. 275 (17): 13012–6. doi:10.1074/jbc.275.17.13012. PMID10777604.
Turner FB, Taylor SM, Moran RG (2000). "Expression patterns of the multiple transcripts from the folylpolyglutamate synthetase gene in human leukemias and normal differentiated tissues". J. Biol. Chem. 275 (46): 35960–8. doi:10.1074/jbc.M005228200. PMID10964921.
Leclerc GJ, Barredo JC (2001). "Folylpoly-gamma-glutamate synthetase gene mRNA splice variants and protein expression in primary human leukemia cells, cell lines, and normal human tissues". Clin. Cancer Res. 7 (4): 942–51. PMID11309345.
Wang Y, Zhao R, Goldman ID (2003). "Decreased expression of the reduced folate carrier and folypolyglutamate synthetase is the basis for acquired resistance to the pemetrexed antifolate (LY231514) in an L1210 murine leukemia cell line". Biochem. Pharmacol. 65 (7): 1163–70. doi:10.1016/S0006-2952(03)00007-8. PMID12663051.
Odin E, Wettergren Y, Nilsson S, et al. (2004). "Altered gene expression of folate enzymes in adjacent mucosa is associated with outcome of colorectal cancer patients". Clin. Cancer Res. 9 (16 Pt 1): 6012–9. PMID14676127.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Wettergren Y, Odin E, Nilsson S, et al. (2006). "Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients". Cancer Detect. Prev. 29 (4): 348–55. doi:10.1016/j.cdp.2005.06.006. PMID16122883.
Nair JR, McGuire JJ (2005). "Submitochondrial localization of the mitochondrial isoform of folylpolyglutamate synthetase in CCRF-CEM human T-lymphoblastic leukemia cells". Biochim. Biophys. Acta. 1746 (1): 38–44. doi:10.1016/j.bbamcr.2005.08.004. PMID16169100.