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Literature summary extracted from

  • Lawrence, S.A.; Titus, S.A.; Ferguson, J.; Heineman, A.L.; Taylor, S.M.; Moran, R.G.
    Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates (2014), J. Biol. Chem., 289, 29386-29396 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.2.17 gene FPGS, sequence comparisons, genotyping, sequence of FPGS cDNAs from hamster cells auxotrophic for thymidine, purine, and glycine, FPGS cytosolic isoform expression in CHO, AUXB1, and AUXB1 cells stably transfected with cDNA for fpgs under a viral promoter, the cFPGStet cell line is made by transfecting the fpgs cDNA that produces only cytosolic FPGS protein under doxycycline control, cytosolic folates are observed in both cFPGStet and mFPGStet cells in the presence of doxycyclin Cricetulus griseus
6.3.2.17 gene FPGS, sequence comparisons, genotyping, sequence of FPGS cDNAs from hamster cells auxotrophic for thymidine, purine, and glycine, FPGS mitochondrial isoform expression in CHO, AUXB1, and AUXB1 cells stably transfected with cDNA for fpgs under a viral promoter. Enzyme expression in the mutant cells can complement the mutants which no longer require supplementation with purines, thymidine, or glycine for survival, the mFPGStet cell line is made by transfecting the fpgs cDNA that produces only mitochondrial FPGS protein under doxycycline control, cytosolic folates are observed in both cFPGStet and mFPGStet cells in the presence of doxycyclin Cricetulus griseus

Protein Variants

EC Number Protein Variants Comment Organism
6.3.2.17 A173S/Q536E cell line V79 compared to wild-type CHO-K1 cells, also with silent polymorphisms at codons 94 and 187 Cricetulus griseus
6.3.2.17 additional information C to T transition at nucleotide 1294 generating a premature stop at codon 432 in AUXB1 mutant cell line. The M7.2 cell line has superphysiologic levels of FPGS protein in both the mitochondria and cytosol Cricetulus griseus
6.3.2.17 R139Q cell line AUXB3 Cricetulus griseus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.3.2.17 cytosol
-
Cricetulus griseus 5829
-
6.3.2.17 mitochondrion
-
Cricetulus griseus 5739
-
6.3.2.17 additional information two mRNAs for the fpgs gene direct isoforms of FPGS to the cytosol and to mitochondria Cricetulus griseus
-
-
6.3.2.17 additional information two mRNAs for the fpgs gene direct isoforms of FPGS to the cytosol and to mitochondria in mouse and human tissues Cricetulus griseus
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.3.2.17 Mg2+ required Cricetulus griseus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.2.17 ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate Cricetulus griseus
-
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
?

Organism

EC Number Organism UniProt Comment Textmining
6.3.2.17 Cricetulus griseus
-
-
-
6.3.2.17 Cricetulus griseus Q924L9 mitochondrial isozyme
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.2.17 ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
-
Cricetulus griseus ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
?

Synonyms

EC Number Synonyms Comment Organism
6.3.2.17 Folylpolyglutamate synthetase
-
Cricetulus griseus
6.3.2.17 FPGS
-
Cricetulus griseus

Cofactor

EC Number Cofactor Comment Organism Structure
6.3.2.17 ATP
-
Cricetulus griseus

General Information

EC Number General Information Comment Organism
6.3.2.17 physiological function folylpoly-gamma-glutamate synthetase (FPGS) catalyzes the addition of multiple glutamates to tetrahydrofolate derivatives, the enzyme is localized in the cytosol and mitochondria and folylpolyglutamates are synthezised in both compartments. Folylpolyglutamates cannot traverse mitochondrial membranes in either direction. Subcellular isoforms of FPGS are required to establish and maintain subcellular folate compartmentalization and function. Mitochondrial folates are a separate metabolic pool not in equilibrium with cytosol. Roles of cytosolic and mitochondrial FPGS in cell growth and survival, overview Cricetulus griseus
6.3.2.17 physiological function folylpoly-gamma-glutamate synthetase (FPGS) catalyzes the addition of multiple glutamates to tetrahydrofolate derivatives, the enzyme is localized in the cytosol and mitochondria, and folylpolyglutamates are synthezised in both compartments. Folylpolyglutamates cannot traverse mitochondrial membranes in either direction. Subcellular isoforms of FPGS are required to establish and maintain subcellular folate compartmentalization and function. Mitochondrial folates are a separate metabolic pool not in equilibrium with cytosol. Mitochondrial FPGS is required because folate polyglutamates are not substrates for transport across the mitochondrial membrane in either direction and that polyglutamation not only traps folates in the cytosol, but also in the mitochondrial matrix. Roles of cytosolic and mitochondrial FPGS in cell growth and survival, overview Cricetulus griseus