Any feedback?
Information on EC 6.3.2.17 - tetrahydrofolate synthase and Organism(s) Arabidopsis thaliana and UniProt Accession F4K2A1
for references in articles please use BRENDA:EC6.3.2.17Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
6.3.2.17 tetrahydrofolate synthaseIUBMB Comments
In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.12, dihydrofolate synthase , the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date . In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes . As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in ). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
Specify your search results
Word Map
- 6.3.2.17
- methotrexate
- antifolate
- thymidylate
- leukemia
-
polyglutamylation
-
folate-dependent
-
ccrf-cem
-
one-carbon
- aminopterin
- casei
- glycinamide
-
mtx-resistant
- methylenetetrahydrofolate
- monoglutamate
-
ddathf
- trimetrexate
-
transformylase
- pemetrexed
- raltitrexed
-
formyltransferase
- leucovorin
- 7-hydroxymethotrexate
-
poly-gamma-glutamylation
- 5,10-methylenetetrahydrofolate
- pentaglutamate
- 5-formyltetrahydrofolate
- garft
- 5,10-dideazatetrahydrofolate
- quinazoline
- lometrexol
- tomudex
-
folate-based
-
methotrexate-resistant
- triglutamate
- tetraglutamate
- dihydropteroate
-
monoglutamylated
- analysis
- pteroylmonoglutamate
- medicine
-
n10-propargyl-5,8-dideazafolic
- pharmacology
The taxonomic range for the selected organisms is: Arabidopsis thaliana
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
folylpolyglutamate synthetase, mthfd1l, folylpoly-gamma-glutamate synthetase, folylpolyglutamate synthase, folypolyglutamate synthetase, fpgs1, atdfb, cfpgs, mfpgs, folylpolyglutamyl synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FPGS1
Folate polyglutamate synthetase
-
-
-
-
Folylpoly(.gamma.-glutamate) synthase
-
-
-
-
Folylpoly-.gamma.-glutamate synthase
-
-
-
-
Folylpoly-gamma-glutamate synthetase
-
-
-
-
Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase
-
-
-
-
Folylpolyglutamate synthase
-
-
-
-
Folylpolyglutamate synthetase
Folylpolyglutamyl synthetase
-
-
-
-
Formyltetrahydropteroyldiglutamate synthetase
-
-
-
-
FPGS
N10-Formyltetrahydropteroyldiglutamate synthetase
-
-
-
-
Synthetase, folylpolyglutamate
-
-
-
-
Tail length regulator
-
-
-
-
tetrahydrofolate:L-glutamate gamma-ligase (ADP-forming)
-
-
-
-
tetrahydrofolylpolyglutamate synthase
-
-
-
-
Folylpolyglutamate synthetase
-
-
-
-
FPGS
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
carboxylic acid amide formation
-
-
-
-
carboxamide formation
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
tetrahydropteroyl-gamma-polyglutamate:L-glutamate gamma-ligase (ADP-forming)
In some bacteria, a single protein catalyses both this activity and that of EC 6.3.2.12, dihydrofolate synthase [3], the combined activity of which leads to the formation of the coenzyme polyglutamated tetrahydropteroate (H4PteGlun), i.e. various tetrahydrofolates (H4folate). In contrast, the activities are located on separate proteins in most eukaryotes studied to date [4]. In Arabidopsis thaliana, this enzyme is present as distinct isoforms in the mitochondria, the cytosol and the chloroplast. Each isoform is encoded by a separate gene, a situation that is unique among eukaryotes [4]. As the affinity of folate-dependent enzymes increases markedly with the number of glutamic residues, the tetrahydropteroyl polyglutamates are the preferred coenzymes of C1 metabolism. (reviewed in [5]). The enzymes from different sources (particularly eukaryotes versus prokaryotes) have different substrate specificities with regard to one-carbon substituents and the number of glutamate residues present on the tetrahydrofolates.
CAS REGISTRY NUMBER
COMMENTARY
63363-84-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
ATP + 10-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 10-formyl-5,6,7,8-tetrahydropteroyl-Glu2
-
-
-
?
ATP + 5,10-methylene-5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + 5,10-methylene-5,6,7,8-tetrahydrofolyl-Glu
-
-
-
?
ATP + 5,6,7,8-tetrahydrofolic acid + L-glutamate
ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu
-
-
-
?
ATP + 5-formyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 5-formyl-5,6,7,8-tetrahydropteroyl-Glu2
-
-
-
?
ATP + 5-methyl-5,6,7,8-tetrahydropteroylglutamate + L-glutamate
ADP + phosphate + 5-methyl-5,6,7,8-tetrahydropteroyl-Glu2
-
-
-
?
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
isozyme FPGS1 is preferentially expressed in vascular tissues
additional information
strong expression of the enzyme in cotyledons and hypocotyl during early developmental stage, histochemical localization of AtDFB promoter activity and AtDFB expression patterns, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
subcellular localization of the three isoforms of FPGS in Arabidopsis thaliana: FPGS1 is localized in plastid, FPGS2 in mitochondria, and FPGS3 in the cytosol
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
physiological function
the mitochondrial folylpolyglutamate synthetase catalyzes the conjugation of glutamate residues to the tetrahydrofolate during folate synthesis
additional information
malfunction
isozyme FPGS1 can partially compensate for isozyme DFC defect
malfunction
a T-DNA insertion mutant (atdfb-3 or fpgs1) of the plastidial folylpolyglutamate synthetase gene (AtDFB) is defective in seed reserves and skotomorphogenesis. Lower carbon and higher nitrogen content in the mutant seeds compared to wild-type are indicative of an altered C and N partitioning capacity. Higher levels of organic acids and sugars are detected in the mutant seeds compared with the wild-type. Mutant atdfb-3 seeds contain less total amino acids and individual Asn and Glu as well as NO3-. The mutant exhibts significant changes in seed storage. Defects in hypocotyl elongation are observed in atdfb-3 in darkness under sufficient nitrate conditions, and further enhances under nitrate limited conditions. Mutant sensitivity to limited nitrate during a narrow developmental window. Exogenous 5-formyl-tetrahydrofolate completely restores the hypocotyl length in atdfb-3 seedlings with nitrate as the sole N source. Further study demonstrated that folate profiling and N metabolism are perturbed in atdfb-3 etiolated seedlings. The activity of enzymes involved in N reduction and assimilation is altered in atdfb-3. Metabolite profiles in wild-type and atdfb-3 seeds, phenotype, overview
malfunction
a T-DNA insertion mutant (atdfb-3) of the plastidial folylpolyglutamate synthetase gene (AtDFB) is defective in folate metabolism and nitrogen metabolism under nitrate-limited conditions in darkness. Exogenous applied 5-formyl-tetrahydrofolate (5-F-THF) completely restores nitrogen content, soluble protein, total amino acids, individual amino acids including Glu, Gln, Asp, Asn, Pro, Arg and Met, nitrate, and endogenous 5-F-THF in atdfb-3 to the wild-type level. Ser in atdfb-3 is 19.94fold higher than that in the wild-type, the content of 5-F-THF in the wild-type and atdfb-3is 203.40fold and 120.75fold, respectively, of that without 5-F-THF application. At the same time the application of 5-F-THF partially restored the content of Ser and nitrite in the mutant. The mutant phenotype shows atdfb-dramatically shortened hypocotyls, altered nitrogen and folate metabolism under nitrate-limited condition, and exogenous applied 5-F-THF completely restored hypocotyl length in atdfb-3 seedlings with nitrate as the sole nitrogen source
malfunction
loss of function of folylpolyglutamate synthetase 1 reduces lignin content and improves cell wall digestibility in Arabidopsis thaliana. fpgs1 mutants in Arabidopsis show reduced levels of methionine and other C1 metabolic intermediates in young seedlings. Total lignin is low in fpgs1 mutant plants leading to higher saccharification efficiency of the mutant. The decrease in total lignin in fpgs1 is mainly due to lower guaiacyl lignin levels. Glycome profiling reveals subtle alterations in the cell walls of fpgs1, the degree of methylationof 4-O-methyl glucuronoxylan in hemicellulosic polysaccharides is reduced in the fpgs1 mutant, NMR analysis. Transcript profiling of mutant fpgs1 inflorescence stems reveals downregulation of genes in the phenylpropanoid, methylation, and C1 pathways, overview. Phenotype, overview
physiological function
the mitochondrial folylpolyglutamate synthetase catalyzes the conjugation of glutamate residues to the tetrahydrofolate during folate synthesis
physiological function
in plants, the C1 pathway is crucial for the synthesis of a large number of secondary metabolites, including lignin. Lignin is a complex, polymeric phenylpropanoid-derived compound, which confers mechanical strength to the cell wall by cross-linking different polysaccharides, especially in fibers and tracheary elements. Tetrahydrofolate and its derivatives, collectively referred to as folates, are crucial cofactors for C1 metabolic pathway enzymes. Folylpolyglutamate synthetase (FPGS) catalyzes the addition of a glutamate tail to folates to form folylpolyglutamates. Folate polyglutamylation is carried out by the enzyme folylpolyglutamate synthetase (FPGS). Isozyme FPGS1 has a role in lignocellulosic formation
physiological function
intact folate metabolism is necessary for nitrogen metabolism in Arabidopsis thaliana under nitrate-limited condition in darkness, providing novel insights into function of folate
physiological function
the enzyme is required for seed reserves, hypocotyl elongation, and N metabolism in darkness, providing novel insights into potential associations of folate metabolism with seed reserve accumulation, N metabolism, and hypocotyl development in Arabidopsis thaliana
malfunction
-
disruption of FPGS leads to short primary roots and root hairs. Phenotype is associated with a disorganized quiescent center, dissipated auxin gradient in the root cap, bundled actin cytoskeleton, and reduced cell division and expansion. The root growth and quiescent center defects of mutant are rescued by exogenous application of 5-formyl-tetrahydrofolate
malfunction
deficiency in N utilization in an Arabidopsis thaliana transfer DNA insertion mutant of the mitochondrial folylpolyglutamate synthetase gene DFC. The mutant seedlings display several metabolic changes that are typical of plant responses to low-N stress, including increased levels of starch and anthocyanin synthesis as well as decreased levels of soluble protein and free amino acid, as compared to wild-type seedlings with sufficient external N. Isozyme FPGS1 can partially compensate for isozyme DFC defect. No significant differences in growth, development, or fertility are observed between wild-type and dfc plants in soil
additional information
folate profiles in Arabidopsis seedlings, overview
additional information
folate profiles in Arabidopsis seedlings, overview
additional information
folate profiles in Arabidopsis seedlings, overview
additional information
folate profiles in Arabidopsis seedlings, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). FPGS1_ARATH
571
0
63345
Swiss-Prot
Mitochondrion (Reliability: 3)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of a fpgs1 knockout mutant, transcripts of a number of genes in the C1 and lignin pathways had altered expression in fpgs1 mutants, microarray analysis and quantitative real-time RT-PCR. Total lignin is low in fpgs1 mutant plants leading to higher saccharification efficiency of the mutant. The decrease in total lignin in fpgs1 is mainly due to lower guaiacyl lignin levels. Glycome profiling reveals subtle alterations in the cell walls of fpgs1, the degree of methylation of 4-O-methyl glucuronoxylan in hemicellulosic polysaccharides is reduced in the fpgs1 mutant, NMR analysis
additional information
generation of a T-DNA insertion mutant (atdfb-3) of the plastidial folylpolyglutamate synthetase gene (AtDFB). The mutant is defective in seed reserves and skotomorphogenesis. Lower carbon and higher nitrogen content in the mutant seeds compared to wild-type are indicative of an altered C and N partitioning capacity. Higher levels of organic acids and sugars are detected in the mutant seeds compared with the wild-type. Mutant atdfb-3 seeds contain less total amino acids and individual Asn and Glu as well as NO3-. The mutant exhibts significant changes in seed storage. Defects in hypocotyl elongation are observed in atdfb-3 in darkness under sufficient nitrate conditions, and further enhances under nitrate limited conditions. Mutant sensitivity to limited nitrate during a narrow developmental window. Exogenous 5-formyl-tetrahydrofolate completely restores the hypocotyl length in atdfb-3 seedlings with nitrate as the sole N source. Further study demonstrated that folate profiling and N metabolism are perturbed in atdfb-3 etiolated seedlings. The activity of enzymes involved in N reduction and assimilation is altered in atdfb-3. Exogenous 5-fluoro-tetrahydrofolate restores the wild-type hypocotyl phenotype in etiolated atdfb-3 mutant seedlings
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the enzyme is a viable target for reducing cell wall recalcitrance in plants
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ravanel, S.; Cherest, H.; Jabrin, S.; Grunwald, D.; Surdin-Kerjan, Y.; Douce, R.; Rebeille, F.
Tetrahydrofolate biosynthesis in plants: molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana
Proc. Natl. Acad. Sci. USA
98
15360-15365
2001
Arabidopsis thaliana
Srivastava, A.C.; Ramos-Parra, P.A.; Bedair, M.; Robledo-Hernandez, A.L.; Tang, Y.; Sumner, L.W.; Diaz de la Garza, R.I.; Blancaflor, E.B.
The folylpolyglutamate synthetase plastidial isoform is required for postembryonic root development in Arabidopsis
Plant Physiol.
155
1237-1251
2011
Arabidopsis thaliana
Jiang, L.; Liu, Y.; Sun, H.; Han, Y.; Li, J.; Li, C.; Guo, W.; Meng, H.; Li, S.; Fan, Y.; Zhang, C.
The mitochondrial folylpolyglutamate synthetase gene is required for nitrogen utilization during early seedling development in Aarabidopsis
Plant Physiol.
161
971-989
2013
Arabidopsis thaliana (F4J2K2), Arabidopsis thaliana (F4K2A1)
Meng, H.; Xu, B.; Zhang, C.; Jiang, L.
Arabidopsis plastidial folylpolyglutamate synthetase is required for nitrogen metabolism under nitrate-limited condition in darkness
Biochem. Biophys. Res. Commun.
482
277-281
2017
Arabidopsis thaliana (F4K2A1), Arabidopsis thaliana, Arabidopsis thaliana Col-0 (F4K2A1)
Srivastava, A.C.; Chen, F.; Ray, T.; Pattathil, S.; Pena, M.J.; Avci, U.; Li, H.; Huhman, D.V.; Backe, J.; Urbanowicz, B.; Miller, J.S.; Bedair, M.; Wyman, C.E.; Sumner, L.W.; York, W.S.; Hahn, M.G.; Dixon, R.A.; Blancaflor, E.B.; Tang, Y.
Loss of function of folylpolyglutamate synthetase 1 reduces lignin content and improves cell wall digestibility in Arabidopsis
Biotechnol. Biofuels
8
224
2015
Arabidopsis thaliana (F4K2A1), Arabidopsis thaliana Col-0 (F4K2A1)
Meng, H.; Jiang, L.; Xu, B.; Guo, W.; Li, J.; Zhu, X.; Qi, X.; Duan, L.; Meng, X.; Fan, Y.; Zhang, C.
Arabidopsis plastidial folylpolyglutamate synthetase is required for seed reserve accumulation and seedling establishment in darkness
PLoS ONE
9
e101905
2014
Arabidopsis thaliana (F4K2A1)
EXTERNAL LINKS (specific for EC-Number 6.3.2.17)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
