Folylpolyglutamate synthase

Folylpolyglutamate synthase
Identifiers
Symbol	FPGS
External IDs	OMIM: 136510 MGI: 95576 HomoloGene: 6997 ChEMBL: 3171 GeneCards: FPGS Gene
EC number	6.3.2.17
Gene ontology Molecular function • tetrahydrofolylpolyglutamate synthase activity • ATP binding Cellular component • cytoplasm • mitochondrion • mitochondrial inner membrane • mitochondrial matrix • cytosol Biological process • liver development • nucleobase-containing compound metabolic process • glutamate metabolic process • one-carbon metabolic process • folic acid-containing compound metabolic process • vitamin metabolic process • water-soluble vitamin metabolic process • brain development • organ regeneration • small molecule metabolic process • folic acid metabolic process • tetrahydrofolylpolyglutamate biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2356	14287
Ensembl	ENSG00000136877	ENSMUSG00000009566
UniProt	Q05932	P48760
RefSeq (mRNA)	NM_001018078	NM_010236
RefSeq (protein)	NP_001018088	NP_034366
Location (UCSC)	Chr 9: 127.79 – 127.81 Mb	Chr 2: 32.68 – 32.7 Mb
PubMed search

Folylpolyglutamate synthase, mitochondrial is an enzyme that in humans is encoded by the FPGS gene.^[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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|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

References

1. "Entrez Gene: FPGS folylpolyglutamate synthase".

Further reading

• Garrow TA, Admon A, Shane B (1992). "Expression cloning of a human cDNA encoding folylpoly(gamma-glutamate) synthetase and determination of its primary structure.". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 9151–5. doi:10.1073/pnas.89.19.9151. PMC 50083. PMID 1409616.
• Cichowicz DJ, Shane B (1987). "Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme.". Biochemistry 26 (2): 504–12. doi:10.1021/bi00376a024. PMID 3828320.
• 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. PMID 6934068.
• 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. PMID 7721888.
• 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. PMID 8521387.
• 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. PMID 8662720.
• 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. PMID 9312158.
• 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. PMID 10777604.
• 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. PMID 10964921.
• 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. PMID 11309345.
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• 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. PMID 12663051.
• 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. PMID 14676127.
• 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. PMID 14702039.
• 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. PMID 16122883.
• 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. PMID 16169100.
• Leclerc GJ, Leclerc GM, Kinser TT, Barredo JC (2006). "Analysis of folylpoly-gamma-glutamate synthetase gene expression in human B-precursor ALL and T-lineage ALL cells.". BMC Cancer 6: 132. doi:10.1186/1471-2407-6-132. PMC 1513244. PMID 16707018.