Literature summary for 6.3.2.17 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 .

Cloned(Commentary)

Cloned (Comment)	Organism
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
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

Cloned (Comment)

Organism

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

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

Protein Variants	Comment	Organism
A173S/Q536E	cell line V79 compared to wild-type CHO-K1 cells, also with silent polymorphisms at codons 94 and 187	Cricetulus griseus
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
R139Q	cell line AUXB3	Cricetulus griseus

Localization

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

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Cricetulus griseus

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Cricetulus griseus	-	-	-
Cricetulus griseus	Q924L9	mitochondrial isozyme	-

Substrates and Products (Substrate)

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

Synonyms

Synonyms	Comment	Organism
Folylpolyglutamate synthetase	-	Cricetulus griseus
FPGS	-	Cricetulus griseus

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Cricetulus griseus

General Information

General Information	Comment	Organism
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
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